@article {pmid42770545,
year = {2026},
author = {Leonenko, G and Mavromati, K and Hughes, L and Sundarakumar, JS and Brookes, K and Morgan, K and Quinn, T and Escott-Price, V and , },
title = {Genetic Resilience and Resistance in Alzheimer's Disease Diagnosis and Pathology.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78367},
pmid = {42770545},
issn = {1531-8249},
abstract = {OBJECTIVE: Some individuals avoid Alzheimer's disease (AD) pathology as they age, or retain cognition despite substantial pathology, suggesting mechanisms of resistance or resilience to neurodegeneration. Educational attainment (EA) is associated with reduced risk of cognitive decline, although the underlying mechanisms remain unclear. We investigated whether genome-wide polygenic scores (GPS) based on cognitive and non-cognitive components of EA, reflecting intelligence and behavioral/social traits, respectively, show differential associations with AD diagnosis and neuropathology.

METHODS: Associations between GPS for cognitive and non-cognitive components of EA and AD outcomes were examined across four cohorts: two cohorts included living participants with biomarker assessments (BioHermes-1, n = 770; Alzheimer's Disease Neuroimaging Initiative [ADNI], n = 1,361), and two included postmortem neuropathological evaluations (Religious Orders Study and Rush Memory and Aging Project [ROSMAP], n = 841; Brain for Dementia Research [BDR], n = 511). Outcomes included clinical diagnosis, amyloid status, plasma neurodegenerative biomarkers, and neuropathological measurements.

RESULTS: We found a significant negative association between cognitive EA GPS and clinical diagnosis of AD across all four cohorts and with Braak stage in ROSMAP and BDR cohorts. In contrast, the GPS for non-cognitive component of EA showed no significant association with AD diagnosis, neurodegenerative plasma biomarkers or amyloid positron emission tomography (PET) status and the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) scores.

INTERPRETATION: These results suggest a brain maintenance mechanism that supports the brain's ability to resist to changes in neuronal integrity. This indicates that interventions focused on increasing EA solely by additional years of schooling are unlikely to affect AD incidence, whereas alternative approaches targeting the cognitive component of EA (intelligence) may offer greater potential for prevention. ANN NEUROL 2026.},
}

@article {pmid42770547,
year = {2026},
author = {Cho, G and Chen, A and Choi, E and Buxton, OM and Kay, D and Mecca, A and Miner, B},
title = {An Investigation of Sleep Macro- and Microarchitecture by APOE Genotype.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78312},
pmid = {42770547},
issn = {1531-8249},
abstract = {OBJECTIVES: Apolipoprotein E ε4 (APOE ε4), a robust genetic risk factor for Alzheimer's disease (AD) is associated with functional connectivity deficits and amyloid pathology in brain regions involved in sleep regulation. Thus, alterations in sleep architecture may be one pathway through which ε4 contributes to Alzheimer's disease vulnerability. However, sleep architecture characteristics associated with APOE ε4 remain poorly characterized.

METHODS: This cross-sectional study examined associations between APOE genotype and sleep architecture among adults aged 50-85 years enrolled in the Sleep Heart Health Study (N = 3,081). APOE genotype was classified into ε4 heterozygotes, ε4 homozygotes, ε2 carriers, and ε3 homozygotes (reference group). Sleep architecture was defined using macro-level traits (percentage of time spent in in each sleep stage and wake after sleep onset) and micro-level traits (spindle characteristics [power, density, and frequency], odds ratio product [ORP], and arousal index). Associations between APOE genotype and each sleep metric was evaluated using linear regression.

RESULTS: Macroarchitecture was largely comparable across genotypes. However, substantial differences in micro-level traits were identified, including lower spindle power among ε4 homozygotes (β = -2.14, p = 0.02) and a dose-response decrease in spindle frequency at peak power with each ε4 count (βε4 heterozygotes = -0.04, p = 0.04; βε4 homozygote = -0.12, p = 0.065). Both ORP and arousal index decreased in a dose-response pattern with each ε4 count (ORP, βε4-heterozygosity = -0.03, βε4-homozygosity = -0.07, all p < 0.01; arousal index, βε4-heterozygosity = -1.02, p = 0.006, βε4-homozygosity = -1.78, p = 0.07). Between-genotype differences in ORP widened with age. Associations did not vary by sex, race, cognitive status, pTau181, or Aβ42:40 ratio.

INTERPRETATION: Abnormal spindle activity observed among ε4 carriers may contribute to their elevated Alzheimer's disease risk. ε4 carriers also showed less sleep fragmentation, which may reflect diminished arousability or electroencephalogram slowing due to neurodegenerative changes. ANN NEUROL 2026 ANN NEUROL 2026.},
}

@article {pmid42770581,
year = {2025},
author = {Hanna, KJ and Jared, B and Langford, M and Rodoli, WJ},
title = {Lifting Up Dementia Caregivers Through Faith Community Nursing.},
journal = {Journal of Christian nursing : a quarterly publication of Nurses Christian Fellowship},
volume = {42},
number = {2},
pages = {94-101},
pmid = {42770581},
issn = {0743-2550},
mesh = {Humans ; *Caregivers/psychology ; *Parish Nursing ; *Dementia/nursing ; *Christianity ; *Community Health Nursing ; *Alzheimer Disease/nursing ; United States ; Self Care/psychology ; },
abstract = {The Alzheimer's Association reported in 2023 that more than 11 million people in the United States are caregivers of individuals with Alzheimer's or other types of dementia. Caregivers experience higher rates of depression, anxiety, social isolation, and suicidal ideation as well as complicated grief and increases in physical ailments. Faith community nurses are in a prime position to offer support and have the tools, expertise, and insight to help caregivers. Practical advice for wholistic self-care for caregivers as well as interventions to support care navigation is provided in this article.},
}

Humans
*Caregivers/psychology
*Parish Nursing
*Dementia/nursing
*Christianity
*Community Health Nursing
*Alzheimer Disease/nursing
United States
Self Care/psychology

@article {pmid42770782,
year = {2026},
author = {Mitchell, SL and Mor, V and Allore, HG and Travison, TG and McCarthy, EP and Unroe, KT and Gaugler, JE and Harrison, J and Brody, AA},
title = {Designing Pilot Studies for Embedded Pragmatic Clinical Trials.},
journal = {NEJM evidence},
volume = {5},
number = {10},
pages = {EVIDctw2500331},
doi = {10.1056/EVIDctw2500331},
pmid = {42770782},
issn = {2766-5526},
mesh = {Humans ; Pilot Projects ; *Pragmatic Clinical Trials as Topic/methods ; *Research Design ; United States ; Alzheimer Disease/therapy ; Dementia/therapy ; },
abstract = {AbstractEmbedded pragmatic clinical trials (ePCTs) conducted in health care systems are designed to test the effectiveness of interventions under real-world conditions and accelerate their adoption into clinical practice. ePCTs have distinct features compared with traditional randomized controlled trials, and investigators are still gaining experience designing and conducting them. Poorly executed ePCTs lead to invalid results, wasted resources, reluctance of health care systems to partner in research, and delays translating effective care into practice. Demonstrating ePCTs are feasible before embarking on them is essential. The National Institute on Aging IMbedded Pragmatic Alzheimer's Disease (AD) and AD-Related Dementias Clinical Trials (IMPACT) Collaboratory was established in 2019 to build national capacity to conduct ePCTs in dementia care. Over 5 years, IMPACT funded 23 pilot ePCTs. Drawing on that experience, this Clinical Trials Workshop reviews a practical approach for designing pilot ePCTs.},
}

Humans
Pilot Projects
*Pragmatic Clinical Trials as Topic/methods
*Research Design
United States
Alzheimer Disease/therapy
Dementia/therapy

@article {pmid42770826,
year = {2026},
author = {Phan, TTH and Huang, TT and Doan, TKH and Nguyen, PTN and Ho, TB and Shyu, YL},
title = {Analytical Appraisal of Validity and Reliability Metrics in Dementia Knowledge Assessment Instruments: Consequences for Clinical Nursing Practice in Vietnam.},
journal = {Research in gerontological nursing},
volume = {},
number = {},
pages = {1-8},
doi = {10.3928/19404921-20260916-02},
pmid = {42770826},
issn = {1938-2464},
abstract = {PURPOSE: To validate and compare the psychometric properties of the Alzheimer's Disease Knowledge Scale Vietnam Version (ADKS-V), Dementia Knowledge Assessment Tool Version Two (DKAT2-V), and 27-item Dementia Knowledge Assessment Scale Vietnam Version (DKAS-V).

METHOD: A cross-sectional study surveyed 360 community-dwelling older adults and 394 primary care nurses in Ho Chi Minh City.

RESULTS: The scales demonstrated strong content validity (.86 to .91), convergent validity (r = .698 to .770), and reliability (Kuder-Richardson 20 [KR-20] = .765 to .820, ω = .793 to .849). Unidimensional confirmatory factor analysis (CFA) fit was poor. In contrast, target-population-specific orthogonal bifactor CFA models confirmed superior fit (comparative fit index = .939 to .981, root mean square error of approximation = .031 to .049) over unidimensional structures. High general factor strength (ωH = .571 to .811) and negligible specific subscale variance (mostly <.15) justified single composite scoring.

CONCLUSION: All three Vietnamese versions are culturally appropriate and robust. We recommend DKAT2-V for nursing education, ADKS-V for community screening, and DKAS-V as a universal epidemiological tool.},
}

@article {pmid42771220,
year = {2026},
author = {Li, K and Si, Q and Zhang, C and Zhang, C and Wang, M and Liu, J and Zhao, J and Xing, H and Liu, J},
title = {Dysregulated polyamine metabolism in neurological disorders: molecular mechanisms and therapeutic opportunities.},
journal = {Molecular biology reports},
volume = {53},
number = {1},
pages = {},
pmid = {42771220},
issn = {1573-4978},
support = {No. YJSCX202502Z//The Graduate Research Innovation Support Program of Henan Medical University/ ; No. GCC2026048//the Henan High-level Talent International Training Project/ ; No. LHGJ20190457//the Henan Provincial Health Commission/ ; No. HNMOTO2025081//the Henan Medical Researcher Overseas Training Program/ ; No. 25A320037//the Key Scientific Research Project Plan of Higher Education Institutions in Henan Province/ ; No. 262300420548//the Henan Natural Science Foundation Project/ ; },
mesh = {Humans ; *Polyamines/metabolism ; *Nervous System Diseases/metabolism ; Oxidative Stress ; Animals ; Autophagy ; Spermidine/metabolism ; },
abstract = {Polyamines (PAs), principally putrescine (Put), spermidine (Spd), and spermine (Spm), are ubiquitous aliphatic polycations that regulate nucleic-acid interactions, ion-channel activity, autophagy, redox balance, proteostasis, and immune signaling. Growing genetic, multi-omics, and experimental evidence indicates that disruption of PA biosynthesis, catabolism, acetylation, and transport contributes to neurological disease. In Alzheimer's disease (AD), altered PA flux intersects with Tau and amyloid-β (Aβ) pathology, methylation imbalance, oxidative stress, and impaired autophagic clearance. In Parkinson's disease (PD), PA transport and interconversion are linked to lysosomal dysfunction, mitochondrial stress, and α-synuclein toxicity; ATP13A2-associated Kufor-Rakeb syndrome further illustrates the neurological consequences of defective lysosomal PA transport. PA dysregulation is also implicated in amyotrophic lateral sclerosis (ALS), diabetic retinopathy, Snyder-Robinson syndrome, epilepsy, Bachmann-Bupp syndrome, and cerebral ischemia. This review integrates disease-specific evidence with four interconnected mechanisms-autophagy, oxidative stress, proteostasis, and neuroinflammation-and discusses therapeutic approaches including direct Spd administration, modulation of PA-metabolic enzymes and transporters, and combination strategies. Because PAs can exert both protective and toxic effects depending on concentration, cellular compartment, and disease context, translation will require CNS-relevant biomarkers, dose and route optimization, and explicit consideration of blood-brain barrier constraints.},
}

Humans
*Polyamines/metabolism
*Nervous System Diseases/metabolism
Oxidative Stress
Animals
Autophagy
Spermidine/metabolism

@article {pmid42771289,
year = {2026},
author = {Dagdelen, B and Ozguncu, C and Zamani, AG and Arikoglu, H},
title = {APOE ε4 variant interpretation and protein numbering discrepancy: a case report.},
journal = {Molecular biology reports},
volume = {53},
number = {1},
pages = {},
pmid = {42771289},
issn = {1573-4978},
mesh = {Humans ; Male ; *Apolipoprotein E4/genetics ; High-Throughput Nucleotide Sequencing/methods ; Middle Aged ; *Alzheimer Disease/genetics ; Alleles ; Polymorphism, Single Nucleotide/genetics ; Genetic Predisposition to Disease ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia worldwide, and the apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for late-onset form. Differences in protein numbering conventions may complicate recognition of clinically important variants during genomic interpretation.

METHODS: We report a 57-year-old man with early-onset AD who underwent next-generation sequencing (NGS). Genetic findings were interpreted using transcript, protein, and dbSNP annotations to assess the clinical significance of the identified variant.

RESULTS: NGS identified a homozygous APOE variant annotated as p.Cys130Arg. This annotation corresponds to the APOE ε4-defining rs429358 variant, commonly reported as Cys112Arg in the mature protein sequence. The variant was initially classified as a variant of uncertain significance (VUS) in the clinical genetic report. Subsequent review demonstrated that p.Cys130Arg and Cys112Arg represent equivalent annotations of the same rs429358 allele.

CONCLUSIONS: This case highlights how alternative protein numbering conventions may complicate variant interpretation and underscores the importance of integrating genomic, transcript, protein, and dbSNP-level information during clinical genomic analysis.},
}

Humans
Male
*Apolipoprotein E4/genetics
High-Throughput Nucleotide Sequencing/methods
Middle Aged
*Alzheimer Disease/genetics
Alleles
Polymorphism, Single Nucleotide/genetics
Genetic Predisposition to Disease

@article {pmid42771693,
year = {2026},
author = {Tariot, PN and Citrome, L and Clevenger, CK and Jackson, WC and Montano, CB and Patel, A and Porsteinsson, AP and Sabbagh, M},
title = {Targeted Treatment of Agitation in Alzheimer's Dementia: Prioritizing Function and Safety Over Sedation and Other Serious Harms.},
journal = {The primary care companion for CNS disorders},
volume = {28},
number = {5},
pages = {},
doi = {10.4088/PCC.haadachi2603},
pmid = {42771693},
issn = {2155-7780},
mesh = {Humans ; *Alzheimer Disease/complications/drug therapy ; *Psychomotor Agitation/drug therapy/etiology/therapy ; Primary Health Care ; *Hypnotics and Sedatives/therapeutic use/adverse effects ; *Antipsychotic Agents/therapeutic use/adverse effects ; },
abstract = {Agitation is a common and clinically significant neuropsychiatric condition in Alzheimer's dementia. Clinicians across the spectrum of care settings frequently encounter agitation but often lack practical clinical guidance. In April 2026, a consensus panel of clinical experts reviewed the literature and developed guidance for managing agitation in Alzheimer's dementia. The panel emphasized the critical role of primary care in agitation management and discussed different treatment approaches for optimizing patient and caregiver outcomes. Treatment should prioritize reduction of patient and caregiver distress and preservation of function rather than mere sedation. Discussion of neurobiology focused on the evolving models of frontal-limbic imbalance as the key driver of agitation in progressing Alzheimer's disease and implications for pharmacologic selection. The panel reviewed evidence on safety and efficacy of pharmacologic agents commonly used in agitation management and concluded that efficacy and safety profiles should guide clinical decision-making. The panel recommended conducting a behavioral assessment using validated tools, ruling out reversible causes, and using nonpharmacologic interventions as the first-line approach prior to starting pharmacologic treatment. Finally, setting-specific considerations were discussed. These recommendations complement prior guidance with a primary-care clinical decision pathway that matches treatment to the neurobiology of agitation and to comparative safety profiles, and that extends to the assessment, documentation, and coding clinicians need at the point of care. The goal is to help clinicians select evidence-based interventions for agitation in Alzheimer's dementia that prioritize safety, alertness, functional engagement, and caregiver well-being while minimizing the serious harms that have historically accompanied off-label management in this population, including excess mortality, cerebrovascular events, cognitive impairment, falls, and sedation. Prim Care Companion CNS Disord 2026;28(5):haadachi2603.},
}

Humans
*Alzheimer Disease/complications/drug therapy
*Psychomotor Agitation/drug therapy/etiology/therapy
Primary Health Care
*Hypnotics and Sedatives/therapeutic use/adverse effects
*Antipsychotic Agents/therapeutic use/adverse effects

@article {pmid42771764,
year = {2026},
author = {Tumbajoy-Arango, CV and Trujillo, N and Sánchez, JP and Díaz, DC and Valencia, S and Trujillo, S and Gómez, D},
title = {Social Determinants and Brain Health in PSEN1 E280A Carriers vs Non-Carriers: A Colombian Cohort.},
journal = {American journal of Alzheimer's disease and other dementias},
volume = {41},
number = {},
pages = {15333175261492405},
doi = {10.1177/15333175261492405},
pmid = {42771764},
issn = {1938-2731},
mesh = {Humans ; Colombia ; Female ; Male ; *Alzheimer Disease/genetics ; *Presenilin-1/genetics ; Middle Aged ; *Social Determinants of Health/statistics & numerical data ; *Brain ; Cohort Studies ; Heterozygote ; Aged ; Subjective Stress ; Adult ; Educational Status ; Mutation ; },
abstract = {Social determinants of health (SDOH), including education, socioeconomic status, place of residence, genetic risk, and perceived stress, influence brain health and Alzheimer's disease (AD), yet their role in genetically at-risk populations remains underexplored. This study examined the influence of SDOH on early brain health, specifically its cognitive dimension, in Colombian individuals from the world's largest kindred with autosomal dominant AD (ADAD) caused by the PSEN1 E280A mutation. Participants included 86 mutation carriers and 71 non-carriers. Brain health was assessed using the BHA_CS index from the TabCAT battery, and perceived stress using the PSS-14. Carriers showed significantly lower brain health and higher perceived stress than non-carriers. Multiple regression analyses identified genetic status, age, education, and place of residence as significant predictors of brain health, with higher education and urban residence associated with better performance. These results demonstrate that SDOH contribute to early cognitive variability even decades before clinical onset in ADAD.},
}

Humans
Colombia
Female
Male
*Alzheimer Disease/genetics
*Presenilin-1/genetics
Middle Aged
*Social Determinants of Health/statistics & numerical data
*Brain
Cohort Studies
Heterozygote
Aged
Subjective Stress
Adult
Educational Status
Mutation

@article {pmid42771783,
year = {2026},
author = {Ruan, JY and Qi, X and Wu, B},
title = {Aggression and violence towards informal dementia caregivers: a call for recognition and action.},
journal = {Age and ageing},
volume = {55},
number = {9},
pages = {},
doi = {10.1093/ageing/afag292},
pmid = {42771783},
issn = {1468-2834},
support = {1P50MD017356-01//Rutgers-NYU Center for Asian Health Promotion and Excellence under NIH/NIMHD/ ; },
mesh = {Humans ; *Caregivers/psychology/legislation & jurisprudence ; *Dementia/therapy/psychology/diagnosis ; *Aggression/psychology ; *Violence/psychology/prevention & control ; Risk Factors ; Social Stigma ; Health Knowledge, Attitudes, Practice ; },
abstract = {Family caregivers are the backbone of dementia care worldwide, yet their safety remains largely absent from discussions of dementia-related aggression and violence. This commentary outlines the multidimensional sources and underlying causes of aggression and violence towards informal caregivers in dementia care, highlighting the need for greater recognition across research, practice, policy and public discourse. First, research must move beyond the assumption that violence in dementia care is primarily a problem affecting formal care staff or people living with dementia themselves. Second, clinical and social care systems must recognise caregiver safety as an integral component of dementia care. Third, policy must explicitly frame aggression and violence towards informal dementia caregivers as both a public health and safeguarding concern. Fourth, public awareness efforts must challenge the silence and stigma surrounding this issue. By bringing caregiver safety into the centre of dementia care debates, this commentary calls for a more comprehensive and ethically responsive approach to supporting families affected by dementia.},
}

Humans
*Caregivers/psychology/legislation & jurisprudence
*Dementia/therapy/psychology/diagnosis
*Aggression/psychology
*Violence/psychology/prevention & control
Risk Factors
Social Stigma
Health Knowledge, Attitudes, Practice

@article {pmid42771911,
year = {2026},
author = {Zhang, Q and Zhang, D and Zhou, R and Zhao, K and Wang, D and Yao, H and Zhou, B and Lu, J and Zhang, X and Han, Y and Wang, P and Liu, Y and Zong, F},
title = {Macro-Micro structural integration for characterizing severity-related structural alterations in mild cognitive impairment.},
journal = {NeuroImage. Clinical},
volume = {52},
number = {},
pages = {104065},
doi = {10.1016/j.nicl.2026.104065},
pmid = {42771911},
issn = {2213-1582},
abstract = {Mild cognitive impairment (MCI) is a clinically heterogeneous condition characterized by substantial variation in structural abnormalities and cognitive impairment. However, existing neuroimaging-based approaches are limited by insufficient modeling of coordinated gray-white matter alterations and vulnerability to site effects in multi-center data. Here, we propose a Macro-Micro Structural Integration (MMSI) framework for characterizing structural-deviation heterogeneity and identifying imaging-derived MCI subgroups. The framework integrates gray-matter morphological features derived from structural magnetic resonance imaging and white-matter microstructural features derived from diffusion MRI. A Dual-Condition Variational Autoencoder was developed to separate biological variation from site-related effects and learn a site-robust normative representation using cognitively normal participants. Tract-specific MMSI scores were subsequently derived to quantify each participant's structural deviation from the normative reference. In a multi-center clinical cohort (N = 860), Gaussian mixture modeling of the tract-wise MMSI profiles identified lower- and higher-deviation MCI subgroups that exhibited significant differences in global cognition, delayed memory, and word recognition. Comparisons with conventional imaging biomarkers, machine-learning classifiers, and statistical harmonization methods further supported the value of the proposed framework. Evaluation in the Alzheimer's Disease Neuroimaging Initiative cohort demonstrated a concordance accuracy of 0.769 between the imaging-derived groups and the clinically predefined early- and late-MCI categories, exceeding the gray matter-only and white matter-only models by 7.7 and 12.3 percentage points, respectively. Transcriptomic association analysis identified KRT77 and CACNA1B as significantly associated with tract-specific MMSI scores after false discovery rate correction. Functional enrichment of the PLS-derived MMSI-associated gene set implicated biological processes related to neural signal transduction, learning and memory, calcium signaling, and immune responses. Together, these findings indicate that the MMSI framework provides a site-robust and interpretable approach for characterizing cross-sectional structural-deviation heterogeneity in MCI and offers preliminary biological support for the identified imaging patterns.},
}

@article {pmid42772054,
year = {2026},
author = {Usmani, MW and Rahim, A and Farid, F and Mahmoud, ERI and Hayat, A and Wang, J},
title = {Next-generation optical biosensors for ultra-early detection of Alzheimer's and Parkinson's diseases: Recent advances, challenges, and future perspectives.},
journal = {Talanta},
volume = {312},
number = {Pt C},
pages = {130609},
doi = {10.1016/j.talanta.2026.130609},
pmid = {42772054},
issn = {1873-3573},
abstract = {Alzheimer's disease (AD) and Parkinson's disease (PD) are considered among the most difficult neurodegenerative diseases because they are progressive, and there are no reliable tools to make early diagnoses. Traditional diagnostic approaches, such as neuroimaging and CSF analysis, are not ideal for rapid clinical screening and are often invasive and costly. Optical biosensors have become attractive platforms for detecting neurodegenerative markers in recent years, offering ultra-sensitivity and minimal invasiveness. Recent advances in optical biosensing technologies for the early detection of key AD and PD biomarkers, such as amyloid-β, tau protein, α-synuclein, dopamine, and neurofilament light chain (NFL), are highlighted. Several photonic techniques, including fluorescence-based assays, surface plasmon resonance (SPR), surface-enhanced Raman scattering (SERS) and whispering-gallery-mode (WGM) microcavity sensors, are critically described, highlighting their sensing mechanisms, analytical performance, and clinical applications. Significant focus is placed on nanostructured SERS substrates, microfluidically integrated platforms, paper-based optical chips, and WGM microlaser-assisted immunosensors for femtomolar-to-attomolar detection in clinically relevant biofluids. Moreover, the use of sophisticated nanomaterials and artificial intelligence-based data analysis is discussed as an effective approach to developing multiplexed, portable, and point-of-care diagnostics. Finally, the challenges and future directions in translating next-generation optical biosensors for the diagnosis of neurodegenerative diseases are discussed.},
}

@article {pmid42772093,
year = {2026},
author = {Gomha, SM and Zareen, W and Ismail, MA and Şenol, AM and Ahmed, N and Zaki, MEA and Shafiq, Z},
title = {Synthesis, spectroscopic and DFT investigation of a dual-fluorophore methylene blue-naphthalimide probe for selective Cu[2+] ions sensing and HeLa cell imaging.},
journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy},
volume = {366},
number = {},
pages = {128813},
doi = {10.1016/j.saa.2026.128813},
pmid = {42772093},
issn = {1873-3557},
abstract = {Cu[2+] ions are essential trace elements in biological systems. Any imbalance in their level leads to serious neurodegenerative diseases like Wilson's disease, Parkinson's disease, and Alzheimer's disease. In addition, Cu[2+] ion pollution from the environment can cause further health problems. Therefore, developing sensitive and selective detection approaches for Cu[2+] ions is of particular significance. In this work, we designed, synthesized, and utilized a new fluorescent probe (MB-M) based on fluorophores methylene blue (MB) and 1,8-naphthalimide (M) for the specific detection of Cu[2+] ions in physiological conditions. As a result of interaction with Cu[2+], amide bond cleavage occurs without coordination of the probe to the ion, and both fluorophores are released simultaneously resulting in dual fluorescence signal generation in green and red regions. The probe showed high selectivity and sensitivity (LOD 0.19 μM for MB and 2.0 μM for M) towards Cu[2+] ions in PBS buffer solution at pH 7.4 with 30% ethanol content and fast response time. DFT calculations supported the proposed sensing mechanism, revealing a small HOMO-LUMO energy gap (2.215 eV) and high softness (0.451 eV[-1]) for MB-M. Fluorescent imaging studies and HeLa cell imaging further demonstrated the probes' possible applications as instant recognition and the real-time detection of Cu2+ ions in biological systems. These findings demonstrate that MB-M is a promising fluorescent probe for Cu2+ ions ion detection.},
}

@article {pmid42772130,
year = {2026},
author = {Greco, P and Lazar, AN and Lugli, F and Albonetti, C and Bystrenova, E and Bianchi, M and Fadiga, L and Zerbetto, F and Biscarini, F},
title = {Microfluidic confinement enables monitoring of oligomeric forms of 1-40 β-amyloid peptide in kinetic study by AFM.},
journal = {Journal of colloid and interface science},
volume = {727},
number = {},
pages = {141599},
doi = {10.1016/j.jcis.2026.141599},
pmid = {42772130},
issn = {1095-7103},
abstract = {Amyloid aggregates are hallmarks of a variety of pathologies. The amyloid beta (A-β), aggregates are critical actors in the pathophysiological process of Alzheimer's disease (AD). Understanding their mechanism of growth at the early stages, in terms of intermolecular and environmental factors, may help to identify critical compounds at the nanoscale and potentially new therapeutic targets. Mesoscopic confinement is a strong factor affecting the kinetics of nucleation and growth. Hence, we use microfluidics to mimic the confinement effects on nucleation kinetics and to control in space and time the concentration and the deposition rate of A-β 1-40 peptide. Atomic force microscopy (AFM) reveals the presence of four types of aggregates, classified by mean size and shape; without evidence of fibrils in the 24 h observation window, which instead appear when the substrate is incubated with the bulk solution. The distribution of aggregates on the mica surface changes with the incubation time and depends on the initial concentration of A-β 1-40. We model the kinetics of nucleation and aggregate growth assuming adsorption of a first monolayer and successive nucleation and growth by dynamic conversion between four different forms of aggregates. The concentration dependence of the total volume of amyloid aggregates exhibits a power law dependence whose exponent is approximately 4. This value translates into the smallest stable oligomer size made of four molecules. Molecular dynamics in aqueous solution further show enhanced intrinsic stabilization of the tetramer relative to smaller oligomers, associated with a nonlinear increase in hydrogen bonds and salt bridges. These results show that, in confined conditions, the smallest stable aggregate of A-β 1-40 is the tetramer, underlining the potential role of these small polymorphs in the neuropathological process and prompting them as targets for in-vitro studies.},
}

@article {pmid42772175,
year = {2026},
author = {Berntsson, E and Paul, S and Jarvet, J and Vosough, F and Barth, A and Gräslund, A and Wärmländer, SKTS},
title = {6-gingerol interferes with amyloid-beta (Aβ) peptide aggregation.},
journal = {Biochemical and biophysical research communications},
volume = {837},
number = {},
pages = {153980},
doi = {10.1016/j.bbrc.2026.153980},
pmid = {42772175},
issn = {1090-2104},
abstract = {Alzheimer's disease (AD) is the most prevalent age-related cause of dementia. AD affects millions of people worldwide, and to date there is no cure. The pathological hallmark of AD brains is deposition of amyloid plaques, which mainly consist of amyloid-β (Aβ) peptides, commonly 40 or 42 residues long, that have aggregated into amyloid fibrils. Intermediate aggregates in the form of soluble Aβ oligomers appear to be highly neurotoxic. Cell and animal studies on mice have previously demonstrated positive effects of the molecule 6-gingerol on AD pathology. Gingerols are the main active constituents of the ginger root, which in many cultures is a traditional nutritional supplement for memory enhancement. Here, we use biophysical experiments to characterize in vitro interactions between 6-gingerol and Aβ40/Aβ42 peptides. Our experiments with atomic force microscopy (AFM) imaging show that the hydrophobic 6-gingerol molecule interferes with Aβ aggregation, by interfering with fibril elongation and by promoting formation of amorphous agglomerates. Interestingly, also the DMSO solvent was found to induce formation of amorphous Aβ agglomerates, which appears to be a novel observation. Our experiments with nuclear magnetic resonance (NMR) and Thioflavin-T (ThT) fluorescence spectroscopy show that 6-gingerol has no or very little interaction with Aβ monomers. Taken together, these results might provide a molecular explanation, at least in part, for the previously observed beneficial effects of 6-gingerol on AD pathology. Given its favourable toxicity profile, 6-gingerol appears to have many of the desired properties of an anti-AD compound.},
}

@article {pmid42772203,
year = {2026},
author = {Miceli, F and Soldovieri, MV and Barrese, V and Taglialatela, M},
title = {Kv7 channels as pharmacological targets for central nervous system diseases.},
journal = {Pharmacological reviews},
volume = {78},
number = {6},
pages = {100153},
doi = {10.1016/j.pharmr.2026.100153},
pmid = {42772203},
issn = {1521-0081},
abstract = {Neuronal Kv7 (also known as KCNQ) voltage-gated potassium channels are key regulators of membrane excitability, primarily through their contribution to the M-current, a slowly activating and noninactivating potassium conductance that stabilizes the resting membrane potential and limits repetitive firing. Given the central role of the M-current in regulating critical central nervous system functions, it is not surprising that Kv7 channel dysfunction contributes to the onset and progression of a wide range of neuropsychiatric disorders, and that Kv7 channels are primary targets for pharmacological intervention in all these conditions. In this review, we provide a comprehensive overview of the physiological roles of neuronal Kv7 subunits (Kv7.2-Kv7.5) with particular emphasis on their expression patterns during development and across distinct neuronal populations. We also discuss the complex regulatory mechanisms governing Kv7 channel expression, trafficking, and function, including modulation by intracellular signaling pathways and interacting proteins. Particular attention is devoted to the involvement of Kv7 channel dysfunction in epileptic encephalopathies, pain syndromes, and neuropsychiatric conditions, as well as neurodegenerative disorders such as Alzheimer and Parkinson disease, where altered neuronal excitability is a common pathogenic hallmark. Furthermore, we examine the evolving pharmacological landscape of Kv7 channel modulators, from first-generation openers such as retigabine to next-generation agents, repurposed drugs, natural products, and Kv7 modulators currently in clinical development, highlighting both their therapeutic promise and existing challenges. Collectively, available evidence identifies Kv7 channels as versatile and highly attractive pharmacological targets for the treatment of central nervous system disorders characterized by maladaptive changes in neuronal excitability. SIGNIFICANCE STATEMENT: Kv7 channels are central regulators of neuronal excitability and are increasingly recognized as key therapeutic targets in multiple central nervous system disorders. Advancing our understanding of their pathophysiological role may enable the development of more selective and effective treatments for diseases driven by maladaptive changes in neuronal excitability.},
}

@article {pmid42772562,
year = {2026},
author = {Kumar M J, V and Escarcega, RD and Tan, C and Moruno-Manchon, JF and Urayama, A and Marrelli, SP and Morales, R and McCullough, LD and Kim, N and Jung, SY and Monchaud, D and Tsvetkov, AS},
title = {Stress-induced helicase DHX36 controls neuroinflammation.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {113584},
doi = {10.1016/j.jbc.2026.113584},
pmid = {42772562},
issn = {1083-351X},
abstract = {Neurons in the aging brain experience sustained inflammatory, proteostatic, and genotoxic stress, accompanied by the accumulation of non-canonical nucleic acid structures such as G-quadruplexes (G4s). Using a G4-binding probe and mass spectrometry, we identified the G4 helicase DHX36 enriched in the aged mouse brain, prompting further investigation into its regulation during aging. DHX36 expression was elevated in neurons from aged mouse and human brains and further increased in a tauopathy mouse model and Alzheimer's disease brain. Unexpectedly, pharmacological stabilization of G4s with pyridostatin (PDS) reduced Dhx36 mRNA and protein levels in cultured mouse cortical neurons, indicating that G4 stabilization alone is insufficient to induce DHX36. In contrast, aging-relevant stressors, including inflammatory, ER, and genotoxic stress, robustly increased DHX36 expression and nuclear G4-positive puncta in cultured neurons. Transcriptomic profiling in neurons revealed that DHX36 suppresses neuroinflammatory pathways and modulates genes associated with inflammation, senescence, and chromatin regulation. DHX36 reduced expression of the chromatin architectural factors Hmga1 and Hmga2, identifying them as downstream targets. An ATPase-deficient DHX36 mutant (E335A) reproduced the major transcriptional effects of wild-type DHX36, indicating that they do not require ATP-dependent unwinding. These findings identify DHX36 as a stress-responsive G4 helicase that links aging-relevant stress to transcriptional regulation in neurons and suggest a role in maintaining neuronal homeostasis during aging and neurodegeneration.},
}

@article {pmid42772840,
year = {2026},
author = {Frank, M and Barthélémy, C and Dufour, A and Rivera, S and Baranger, K},
title = {Matrix metalloproteinases (MMPs) in neurodegenerative diseases, an updated overview of the role of MT1-MMP and MT5-MMP in Alzheimer's disease.},
journal = {The Enzymes},
volume = {60},
number = {},
pages = {209-241},
doi = {10.1016/bs.enz.2026.07.004},
pmid = {42772840},
issn = {0423-2607},
mesh = {Humans ; *Alzheimer Disease/enzymology/metabolism ; Animals ; *Neurodegenerative Diseases/enzymology/metabolism ; *Matrix Metalloproteinases/metabolism ; Amyloid beta-Peptides/metabolism ; *Matrix Metalloproteinase 14/metabolism ; },
abstract = {Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and Huntington's disease, pose an increasing threat to global health due to ageing populations and the lack of effective treatments. Matrix metalloproteinases (MMPs), which are proteases that belong to the metzincin superfamily, are critical regulators of neuroinflammation, blood-brain barrier integrity, protein misfolding, synaptic dysfunction and neuronal death. This chapter provides a comprehensive overview of the roles of MMPs at the intersection of the molecular and cellular mechanisms that underpin neurodegenerative processes. The focus is on their pathophysiological mechanisms, therapeutic potential, and recent advances. We highlight novel mechanistic insights in Alzheimer's disease, such as the roles of MT1-MMP and MT5-MMP in amyloid-beta peptide production and the dual functions of MMPs in both neuroprotection and neurotoxicity. This review emphasizes the need for further mechanistic research into the different MMPs involved in neurodegenerative diseases.},
}

Humans
*Alzheimer Disease/enzymology/metabolism
Animals
*Neurodegenerative Diseases/enzymology/metabolism
*Matrix Metalloproteinases/metabolism
Amyloid beta-Peptides/metabolism
*Matrix Metalloproteinase 14/metabolism

@article {pmid42773049,
year = {2026},
author = {McKee, NW and Jing, Y and Serdah, R and Thulasingam, S and Lopez, XS and Tan, EP},
title = {Lipophagy and lipid droplets in neurodegeneration.},
journal = {Trends in pharmacological sciences},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tips.2026.08.004},
pmid = {42773049},
issn = {1873-3735},
abstract = {Lipid droplet (LD) accumulation in neurons and glia is a feature of Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) and is associated with oxidative stress and neuroinflammation. Although protein-targeted monotherapies have achieved partial clinical success, continued disease progression in many patients suggests that additional cellular mechanisms contribute to pathogenesis. Lipophagy, the selective autophagic degradation of LDs, provides a potential clearance route but has been studied primarily in hepatocytes under nutrient deprivation. Recent studies have begun to map noncanonical regulatory mechanisms of lipophagy, identify disease-associated points of failure in AD, PD, and ALS, and report compounds that enhance LD clearance through mechanisms distinct from canonical nutrient sensing. In this article, we review these advances and discuss the emerging rationale for exploring neuron- and context-specific approaches to modulate lipophagy as a complementary strategy in neurodegeneration.},
}

@article {pmid42773069,
year = {2026},
author = {Chiang, PT and Cheng, SY and Hsueh, SJ and Lin, SS and Lee, BC and Liu, CJ and Lin, YH and Huang, SC and Tsai, LK and Tsai, HH},
title = {Clinical utility of combined amyloid biomarkers in early cognitive impairment.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261489619},
doi = {10.1177/13872877261489619},
pmid = {42773069},
issn = {1875-8908},
abstract = {BackgroundEarly etiological diagnosis of cognitive impairment is challenging. Amyloid PET improves diagnostic accuracy but is costly and limited in availability. Plasma phosphorylated tau-217 (p-tau217) has emerged as a scalable, minimally invasive biomarker.ObjectiveThis study aimed to evaluate the diagnostic and prognostic utility of amyloid PET and plasma p-tau217 in older adults with early cognitive impairment.MethodsWe prospectively enrolled 100 adults aged ≥ 65 years with mild cognitive impairment or mild dementia. Participants underwent comprehensive clinical evaluation, brain MRI, [18]F-florbetaben amyloid PET, and plasma p-tau217 analysis. Longitudinal cognitive decline was assessed over a median follow-up of 1.3 years.ResultsAmyloid PET was positive in 45% and resulted in diagnostic revision in 39%. Plasma p-tau217 levels were significantly higher in amyloid-positive individuals (1.178 ± 0.652 versus 0.642 ± 0.940 pg/mL, p < 0.001) and accurately identified amyloid positivity (AUC = 0.855). Both amyloid PET positivity (HR = 6.61, 95% CI 2.36-18.50; p < 0.001) and elevated p-tau217 (HR = 4.43, 95% CI 1.83-10.68; p = 0.001) independently predicted faster cognitive decline. Combined biomarker analysis revealed a stepwise risk stratification, with dual-positive individuals showing the most rapid deterioration (global p < 0.001). Among amyloid-positive patients, elevated p-tau217 further distinguished those with faster progression (p = 0.035).ConclusionsAmyloid PET and plasma p-tau217 provide complementary diagnostic and prognostic value. While PET refines etiological diagnosis, p-tau217 serves as a robust predictor of amyloid status and cognitive trajectory. Integrating these biomarkers improves risk stratification and may facilitate patient selection for disease-modifying therapies.},
}

@article {pmid42773086,
year = {2026},
author = {Man, S and Gao, Y and Mou, K and Gao, Y and Zhang, M},
title = {Mendelian randomization evidence refines retinal alterations in Alzheimer's disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {9},
pages = {e71879},
doi = {10.1002/alz.71879},
pmid = {42773086},
issn = {1552-5279},
}

@article {pmid42773087,
year = {2026},
author = {Ritchie, M and Hussen, K and Langford, O and Donohue, MC and Sano, M and Grill, JD and Aisen, P and Sperling, R and Raman, R},
title = {Research satisfaction among participants in a preclinical Alzheimer's disease trial.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {9},
pages = {e71852},
pmid = {42773087},
issn = {1552-5279},
support = {946223//American Heart Association/ ; U24AG053798//the NIA/ ; R01 AG063689/AG/NIA NIH HHS/United States ; U19AG010483/AG/NIA NIH HHS/United States ; U24AG057437/AG/NIA NIH HHS/United States ; //Eli Lilly/ ; //the Alzheimer's Association/ ; //the Accelerating Medicines Partnership/ ; //Foundation for the National Institutes of Health/ ; //Davis Alzheimer Prevention Program/ ; //Yugilbar Foundation/ ; //anonymous foundation/ ; //GHR Foundation/ ; //Additional private donors to Brigham and Women's Hospital, with in-kind support from Avid Radiopharmaceuticals, Cogstate, Albert Einstein College of Medicine and the Foundation for Neurologic Diseases/ ; },
mesh = {Humans ; *Alzheimer Disease/drug therapy/psychology ; Female ; Male ; Aged ; Surveys and Questionnaires ; *Patient Satisfaction ; Motivation ; },
abstract = {INTRODUCTION: Empirical data capturing participants' experiences in preclinical Alzheimer's disease (AD) trials are limited. We examined participant responses on a Research Satisfaction Survey (RSS) from the Anti-Amyloid Treatment in Asymptomatic AD Study.

METHODS: Participants completed the RSS at week 0, 48, 108, 168, and 240. We examined potential differences in responses by baseline participant characteristics and trial completion status.

RESULTS: RSS scores were high, with > 90% of participants responding positively to all satisfaction items. Across timepoints, altruistic motivations were most frequently affirmed, while study design elements were most frequently disfavored. Affirmation of social motivations increased over time. Participants who responded "not satisfied" at baseline to repeating their decision to enroll had higher odds of study discontinuation than those who responded "satisfied" (1.99; 95% confidence interval [CI]:1.24, 3.19).

DISCUSSION: An RSS captures participant experiences in a preclinical AD trial, can guide decisions on study design features, and may identify those at risk for loss to follow-up.},
}

Humans
*Alzheimer Disease/drug therapy/psychology
Female
Male
Aged
Surveys and Questionnaires
*Patient Satisfaction
Motivation

@article {pmid42773180,
year = {2026},
author = {Harrison, TM and Chadwick, TA and Grothe, MJ and Ward, T and Baker, SL and Landau, SM and Jagust, WJ and , },
title = {Measuring in-vivo tau pathology in the basal forebrain with PET imaging.},
journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology},
volume = {},
number = {},
pages = {},
pmid = {42773180},
issn = {1740-634X},
support = {K01 AG078443//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01 AG034570//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01 AG062689//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01 AG034570//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; U19 AG024904//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; },
abstract = {The basal forebrain (BF) is a site of early tau pathology deposition, and BF cholinergic neurons selectively degenerate in patients with Alzheimer's disease (AD). PET imaging of AD pathology has helped to establish the relationships between early tau in the medial temporal lobe (MTL), amyloid (Aβ) pathology, brain structure and cognition, but it is not clear if PET imaging can be used to similarly characterize early tau pathology in the BF. Here we aim to test the feasibility of measuring tau pathology in the BF in unimpaired older adults with two PET tracers, [[18]F]flortaucipir (FTP) and [[18]F]MK6240, that have unique properties including distinct off-target signal (OTS) patterns. 1397 unimpaired older adult participants with either FTP (n = 509; Berkeley Aging Cohort Study, ADNI) or MK6240 (n = 888; POINTER Imaging study) scans were included and used to quantify tau-PET signal in three ROI categories: the BF, typical temporal tau-PET ROIs (entorhinal cortex [ERC], temporal MetaROI) and OTS ROIs that are adjacent to the BF (thalamus, pallidum). BF and temporal tau burden were associated with global Aβ burden, but OTS was not. BF and MTL tau showed similar associations with age, BF volume, hippocampal volume and multi-domain cognition. Associations were consistent in both FTP and MK6240 cohorts. MTL tau was negatively correlated with BF volume in whole-brain morphometry analyses. Our findings suggest that it is feasible to use PET to measure tau signal in the BF in unimpaired older adults.},
}

@article {pmid42773212,
year = {2026},
author = {Wood Alexander, M and Rabin, JS and Caunca, M and Iadipaolo, A and Cornelis, L and Warrier, R and Walker, KA and Miolane, N and Bot, VA and Wood, B and Oh, HS and Wyss-Coray, T and Pham, A and Borger, J and Diaz, V and Paolillo, EW and Kramer, J and Pritschet, L and Taylor, C and Panizzon, MS and Rea Reyes, RE and Denkinger, MN and Ashton, NJ and Johnson, SC and Jacobs, EG and Saloner, R and Casaletto, KB},
title = {Blood proteomics of menopause map to brain aging and dementia risk.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
pmid = {42773212},
issn = {1546-170X},
abstract = {Menopause is a hallmark process in biological aging that has been implicated in later neurodegenerative risk, but the pathways underlying this connection remain unclear. Here we used blood proteomics data from several cohorts to identify biological changes associated with menopause and its links to brain aging. In n = 80 rigorously staged (STRAW+10) pre-, peri- and postmenopausal women (aged 43-58 years) with serum NULISAseq proteomics, we show that spontaneous menopause is characterized by dysregulation in inflammatory, synaptic, metabolic and Alzheimer's disease biologic processes, which tracked more strongly with hormones than with age. Validation analyses in age-matched pre-/peri- and postmenopausal women (n = 2,814) with plasma Olink proteomics replicated the observed proteomic shifts and revealed broader menopause-related upregulation of inflammatory and catabolic processes plus accelerated organ and cell aging, including brain aging. In four independent cohorts of older women (average age, 60.7-72.1 years; total n = 11,925), higher menopause proteomic scores associated consistently with cognitive aging and dementia risk. The molecular signatures of menopause may inform the selection of biomarkers or therapeutic targets for brain health in midlife women.},
}

@article {pmid42773385,
year = {2026},
author = {Manser, P and Rosio, M and Schmidt, A and Michels, L and de Bruin, ED},
title = {Exergame as medicine? Functional brain adaptations linked to cognitive changes in neurocognitive disorders: exploratory randomized controlled trial.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {42773385},
issn = {2509-2723},
support = {2019-PI06//Stiftung Synapsis - Alzheimer Forschung Schweiz AFS/ ; },
abstract = {Tailored multidomain lifestyle modifications are recommended for reducing dementia risk in mild neurocognitive disorder (mNCD). However, evidence of their capacity to modify disease trajectories and restore functional brain abnormalities remains limited. We aimed to explore functional brain adaptations and correlate underlying cognitive improvements in response to a personalized "exergame as medicine" program ("Brain-IT") for secondary mNCD prevention. Participants were randomized to 12 weeks home-based "Brain-IT" (physical-motor-cognitive with integrated biofeedback breathing training; 120 min/week, moderate intensity) + usual care or usual care alone. Resting-state functional connectivity at the seed(hippocampus)-to-voxel level and task-based full-factorial analysis of variance for functional activation (Blood Oxygenation Level Dependent signal responses) and their correlations with episodic memory performance were analyzed. Data from 32 mNCD participants (71.9 ± 8.1 years; 28% females) with mostly biomarker-supported Alzheimer's etiology (57%) were analyzed. Key findings were significantly (p < 0.0001) reduced hippocampus hyperactivation during memory encoding (partial η[2] = 0.19) and compensatory functional activation increases in the right precuneus (d = 0.76) and middle cingulate gyrus (d = 0.26) that correlated with memory retrieval accuracy changes-all in favor of "Brain-IT." These exploratory findings are consistent with a potential short-term brain-protective role of personalized "exergame as medicine" therapy in mNCD that require confirmation in hypothesis-driven and adequately powered RCTs. Given the overlooked role of exergames in dementia prevention, hybrid implementation-effectiveness research with long-term follow-up measuring biomarker-related and clinical progression should evaluate whether potential brain-protective effects translate to delaying and/or preventing progression to dementia. Registration: https://clinicaltrials.gov/ct2/show/NCT05387057 (May 18, 2022).},
}

@article {pmid42773831,
year = {2026},
author = {Behrens, LL and Kitt-Lewis, E and Crimi, KH and Madrigal, C and Kunselman, AR and Murphy, TE and Kraschnewski, JL and VanHaitsma, KS and Boltz, M},
title = {Feasibility of the DIGNITY Intervention to Support Person-Centered Risk Management in Rural Nursing Homes.},
journal = {Dementia (London, England)},
volume = {},
number = {},
pages = {14713012261485344},
doi = {10.1177/14713012261485344},
pmid = {42773831},
issn = {1741-2684},
abstract = {Honoring individual preferences, like going outside, can enhance the health of nursing home (NH) residents living with Alzheimer's disease and related dementias (ADRD). Although a hallmark of person-centered care, honoring ADRD residents' preferences is often restricted when they are perceived to be high-risk for harm by NH staff. Accessible and efficient strategies are needed to help NH staff balance harmful risks to health and safety against the residents' right to make autonomous choices, especially in under-resourced rural areas. This pilot study (NCT05618678) evaluated the feasibility of Decision-making In aGing and demeNtIa for auTonomY (DIGNITY), a multi-faceted and innovative, theory-based, person-centered risk management intervention aimed at assisting NH staff in respecting the preferences of rural residents living with ADRD, while optimizing safety. Feasibility was assessed using retention rates, staff surveys, and qualitative feedback. Fifty-two NH staff participated (88.7% female, 83.3% White, 94.3% non-Hispanic, and 48% with ≥6 years NH experience), with a 79% retention rate and 87.8% survey response rate. In the DIGNITY group, average scores (on Likert scale of 1-5) indicated high feasibility (3.99), acceptability (4.19), and appropriateness (4.24). Qualitative feedback highlighted the value of in-person training and telemonitoring sessions. The high ratings for feasibility, acceptability, and appropriateness of DIGNITY show its potential for supporting NH staff to more confidently provide person-centered care for ADRD residents.},
}

@article {pmid42773885,
year = {2026},
author = {Han, SH and Faul, JD},
title = {Prosocial helping behaviors attenuate accelerated cognitive decline driven by APOE ε4.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {9},
pages = {e71877},
pmid = {42773885},
issn = {1552-5279},
support = {1R21AG079122//National Institute on Aging at the National Institutes of Health/ ; P30AG066614//National Institute on Aging at the National Institutes of Health/ ; P2CHD042849//Eunice Kennedy Shriver National Institute of Child Health and Human Development at the NIH/ ; },
mesh = {Humans ; *Apolipoprotein E4/genetics ; *Cognitive Dysfunction/genetics/psychology/prevention & control ; *Helping Behavior ; Female ; Male ; Longitudinal Studies ; Aged ; Volunteers/psychology ; *Social Behavior ; },
abstract = {INTRODUCTION: The apolipoprotein E (APOE) ε4 allele accelerates cognitive decline through multiple biological pathways-including neuroinflammatory, vascular, and stress-regulatory mechanisms-yet few modifiable behaviors counter this genetic vulnerability. Prosocial helping engages these same systems in opposing directions, suggesting it may attenuate APOE ε4-related cognitive decline.

METHODS: We analyzed more than two decades of longitudinal data from a large, multiethnic US sample (N = 17,972). Multilevel models that isolate within-person change tested whether transitions in formal volunteering and informal helping moderate APOE ε4-related cognitive decline, while addressing key sources of endogeneity.

RESULTS: Adopting and sustaining formal volunteering attenuated the accelerated cognitive decline typically observed among ε4 carriers, with protective associations evident at modest engagement levels (≤ 4 hours/week). Informal helping was uniquely protective among Hispanic older adults, highlighting the role of cultural context in prosocial engagement.

DISCUSSION: Prosocial helping may be a feasible, scalable strategy for slowing APOE ε4-driven cognitive decline.},
}

Humans
*Apolipoprotein E4/genetics
*Cognitive Dysfunction/genetics/psychology/prevention & control
*Helping Behavior
Female
Male
Longitudinal Studies
Aged
Volunteers/psychology
*Social Behavior

@article {pmid42774029,
year = {2026},
author = {Zhai, Z and Wang, Y and Li, H and Wang, Y and Zhou, J and Liang, Y and Yang, A and Li, Z},
title = {Investigating the DTI-ALPS index and its association with cognitive impairment in Alzheimer's disease: a diffusion tensor imaging study.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1899705},
pmid = {42774029},
issn = {1662-4548},
abstract = {OBJECTIVES: With the global aging population, Alzheimer's disease (AD) poses a major health challenge. The diffusion tensor image (DTI) analysis along the perivascular space (DTI-ALPS) index has emerged as a noninvasive imaging marker that indirectly reflects glymphatic function. However, its alterations in AD and their associations with cognitive impairment remain incompletely understood. This study primarily aimed to investigate changes in the bilateral ALPS index in patients with AD and to evaluate their associations with cognitive, functional, and emotional measures. Secondary analyses further explored white matter microstructural alterations and their relationships with the ALPS index.

MATERIALS AND METHODS: In total, 35 patients with AD and 21 cognitively normal healthy controls (HC) underwent 3.0T MRI and neuropsychological assessments. Tract-based spatial statistics (TBSS) analysis revealed areas of white matter damage and injured fibers in patients. Bilateral ALPS indices were compared between groups using analysis of covariance (ANCOVA) adjusted for age and gender. TBSS and ROI-based ANCOVA analyses of fractional anisotropy (FA) and mean kurtosis (MK) were performed as secondary analyses. Partial correlation analyses were used to examine associations between ALPS indices, white matter metrics, and neuropsychological scores.

RESULTS: Compared with the HC group, the AD group showed significantly lower bilateral ALPS indices, and these differences remained significant after adjustment for age and gender (left: F = 14.404, P < 0.001; right: F = 28.513, P < 0.001). Bilateral ALPS indices were significantly correlated with cognitive and functional measures, including the Mini-Mental State Examination, Montreal Cognitive Assessment, and Activities of Daily Living (ADL), and were also significantly associated with emotional measures, including the Hamilton Anxiety Scale and Hamilton Depression Scale. Among these, the strongest associations were observed with ADL (left: r = 0.688; right: r = 0.701; both P_FDR < 1 × 10-7). Secondary analyses revealed widespread white matter microstructural alterations in AD. Region-of-interest-based analyses showed that the left hippocampal cingulum exhibited significant differences in both FA and MK, and these metrics were positively associated with the ALPS index as well as with cognitive and functional performance.

CONCLUSION: The glymphatic system of AD patients has a reduced ability to clear waste. The ALPS index was closely associated with cognitive, functional, and emotional status, while white matter abnormalities, particularly in the left hippocampal cingulum, may represent a structural correlate of glymphatic dysfunction in AD.},
}

@article {pmid42774078,
year = {2026},
author = {Yuan, Z and Wang, J and Cheng, B and Kuang, Y and Zhang, R and Luo, N and Qiu, S and Liu, Y},
title = {Multimodal network alterations in diagnosis-age-defined early- and late-onset Alzheimer's disease.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1914358},
pmid = {42774078},
issn = {1662-4548},
abstract = {INTRODUCTION: Early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) may differ in large-scale network organization. We compared multimodal MRI markers of diagnosis-age-defined Alzheimer's phenotypes.

METHODS: Alzheimer's Disease Neuroimaging Initiative participants were classified by age at first recorded mild cognitive impairment or Alzheimer's disease diagnosis: <65 years for EOAD and ≥65 years for LOAD. Retrospective symptom-onset information was consistent with this grouping when available. We assessed resting-state functional measures, graph-theoretical nodal metrics, structural-functional coupling (SFC), structural decoupling, and DTI-derived measures. Primary models adjusted for age and sex; sensitivity analyses examined nonlinear age, covariate overlap, clinical severity, disease stage, atrophy, biomarkers, head motion, regional coverage, and control-group composition.

RESULTS: The functional cohort included 50 EOAD, 72 LOAD, and 113 healthy controls. Global mean SFC showed only a modest group effect. LOAD showed higher regional SFC than EOAD in four frontal regions after false discovery rate correction. Graph-theoretical effects were predominantly nominal: only the overall three-group effect in Vermis 9 nodal efficiency survived within-family correction, and no EOAD-versus-LOAD nodal contrast survived. DTI-derived regional measures and structural decoupling were less subtype-discriminative. All four frontal effects remained significant after mean Power framewise displacement adjustment and overlap weighting, with bootstrap confidence intervals excluding zero. However, corrected support narrowed to one region in the nonlinear-age model and disappeared in disease- stage-, APOE ε 4-, amyloid PET-, and centiloid-adjusted models; restriction to amyloid-negative controls also retained one region.

CONCLUSION: In the primary model, diagnosis-age-defined LOAD showed higher frontal regional SFC than EOAD. The absence of corrected EOAD-versus-LOAD graph findings, variable sensitivity-analysis support, and lack of corrected SFC-clinical associations indicate a model-sensitive network phenotype rather than a definitive onset-age biomarker or clinically validated subtype marker.},
}

@article {pmid42774120,
year = {2026},
author = {Gong, C},
title = {Implications of pentose phosphate metabolism and astrocyte co-expression patterns in the pathogenesis of Alzheimer's disease: evidence from artificial intelligence-driven omics and clinical validation.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1887060},
pmid = {42774120},
issn = {1662-4548},
abstract = {BACKGROUND: Metabolic reprogramming in glial cells is increasingly recognized as a pivotal factor in the pathogenesis of AD. While both the pentose phosphate pathway (PPP), a crucial metabolic route for redox balance and biosynthesis, and astrocyte reactivity are implicated in AD, their integrated molecular interaction between processes remains largely uncharted.

METHODS: We employed an integrated multi-omics and artificial intelligence (AI) framework. First, we applied the Limma, WGCNA, and xCell algorithms to bulk RNA-seq profiles from the hippocampus of AD patients to identify a gene signature linking the PPP and astrocyte reactivity (PA). This signature was then used to construct a diagnostic model via an explainable machine learning pipeline and to stratify patients into molecular subtypes through consensus clustering. The central hub gene of this PA-associated signature was subsequently validated using spatially and temporally resolved single-cell data from the AD hippocampus. An AI-based drug-repurposing screen (Drugreflector) and molecular docking simulations were used to identify natural compounds targeting this hub gene for the treatment of AD. Finally, the dysregulation of this target was confirmed by quantifying its expression in peripheral blood samples from a clinical AD cohort.

RESULTS: We identified eight PA-associated gene signatures in AD patients that can help elucidate the pathogenesis and molecular stratification. HDAC3 was identified as the central pathogenic hub, mainly distributed in astrocytes. Through drug screening, nervonic acid was identified as a potential therapeutic agent, showing a high binding affinity to HDAC3. Clinical validation confirmed elevated HDAC3 levels in AD patients.

CONCLUSION: Our study reveals a novel PA-associated molecular axis in AD, with HDAC3 serving as a central epigenetic-metabolic regulator within astrocytes. This co-expression axis provides a framework for patient subtyping, offers a promising diagnostic biomarker, and identifies a potential therapeutic target for AD.},
}

@article {pmid42774131,
year = {2026},
author = {Wang, Y and Cheng, M and Liu, Z},
title = {Age-dependent associations of peripheral inflammatory biomarkers with cognition and brain structural abnormalities in patients with Alzheimer's disease and Alzheimer's disease-related mild cognitive impairment.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1868357},
pmid = {42774131},
issn = {1664-2295},
mesh = {Humans ; Male ; Female ; *Alzheimer Disease/blood/pathology/diagnostic imaging ; Biomarkers/blood ; *Cognitive Dysfunction/blood/pathology ; Aged ; *Inflammation/blood ; Atrophy/pathology ; Age Factors ; *Brain/pathology/diagnostic imaging ; Aged, 80 and over ; *Cognition/physiology ; Magnetic Resonance Imaging ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) is one of the most prevalent neurodegenerative conditions. Chronic peripheral inflammation has been implicated in the pathophysiology of AD. Given their accessibility and cost-effectiveness, peripheral inflammatory biomarkers hold promise as potential indicators for AD. However, their associations with cognitive function and brain structural abnormalities may vary across patients and age groups.

METHODS: Patients diagnosed with AD or AD-related mild cognitive impairment (AD-MCI) were included. Peripheral inflammatory biomarkers, including white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), and monocyte count (MONO), were obtained from complete blood count (CBC). Composite inflammatory biomarkers were calculated from the aforementioned parameters and included the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), neutrophil-to-platelet ratio (NPR), neutrophil-monocyte-to-lymphocyte ratio (NMLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI). We examined the associations of peripheral blood inflammatory biomarkers and calculated composite inflammatory biomarkers with cognitive function, global cortical atrophy, and hippocampal atrophy. Interaction and stratified analyses were employed to investigate the modifying effects of age and sex on these associations.

RESULTS: The study included a total of 395 patients. Within the overall sample, almost all inflammatory biomarkers did not exhibit significant associations with cognitive function, global cortical atrophy, or hippocampal atrophy. Interaction analyses revealed significant interactions between age and several inflammatory biomarkers, while no significant interactions were detected concerning sex. Stratified analyses indicated that among patients younger than 75 years, several composite inflammatory biomarkers were significantly associated with cognitive function, global cortical atrophy, and hippocampal atrophy, whereas no significant associations were observed in patients aged 75 years or older.

CONCLUSION: In patients with AD and AD-MCI, the associations between peripheral inflammatory biomarkers and both cognitive impairment and structural brain abnormalities were found to be age-dependent, with stronger associations observed in patients younger than 75 years. Several composite inflammatory biomarkers showed more consistent associations and may help characterize heterogeneity within this clinical population, although their prognostic and diagnostic value requires further validation.},
}

Humans
Male
Female
*Alzheimer Disease/blood/pathology/diagnostic imaging
Biomarkers/blood
*Cognitive Dysfunction/blood/pathology
Aged
*Inflammation/blood
Atrophy/pathology
Age Factors
*Brain/pathology/diagnostic imaging
Aged, 80 and over
*Cognition/physiology
Magnetic Resonance Imaging

@article {pmid42774284,
year = {2026},
author = {Chatterjee, P and Ivanic, S and Southon, A and McCarthy, C and Patel, SK and Christensen, M and Darby, D and Bush, AI and Ayton, S and Mielke, MM and Werden, E and Brodtmann, A},
title = {Real-world utility of plasma GFAP and NfL in early-onset AD and FTD.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {3},
pages = {e70490},
pmid = {42774284},
issn = {2352-8729},
abstract = {INTRODUCTION: Plasma glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are promising blood biomarkers, but their real-world diagnostic utility in early-onset dementia is understudied.

METHODS: Plasma GFAP, NfL, and phosphorylated tau (p-tau)217 were measured using Simoa in 118 patients with cognitive complaints, clinically classified as non-neurodegenerative conditions (non-ND; n = 52), early-onset Alzheimer's disease (EOAD; n = 39), frontotemporal dementia (FTD; n = 20), or other-neurodegenerative dementia (ND)/ dementia (n = 7). P-tau217 defined Alzheimer's disease pathology.

RESULTS: GFAP was elevated in EOAD compared to non-ND, FTD, and other-ND, and distinguished EOAD from non-ND (area under the curve [95% confidence interval (CI)]: 0.924 [0.871-0.977]) but performed poorly for FTD versus non-ND (0.636 [0.496-0.775]). NfL was most elevated in FTD and EOAD, distinguishing both (FTD: 0.869 [0.778-0.961]; EOAD: 0.770 [0.673-0.867]) from non-ND, but less effective for FTD versus EOAD (0.750 [0.597-0.903]). GFAP appeared stable in severe renal impairment, while NfL increased.

DISCUSSION: These findings support integrating GFAP and NfL into clinical dementia assessments, with GFAP offering added diagnostic specificity in cases of severe renal impairment; however, validation in larger cohorts is needed.},
}

@article {pmid42774443,
year = {2026},
author = {Kumar, A and Fatima, N and Kumar, P and Nath, R and Sachan, AK and Dixit, RK and Pal, R},
title = {To Study the Effect of Nilotinib, a Tyrosine Kinase Inhibitor, on Learning and Memory and Its Comparison with Nitric Oxide Synthase Inhibitor in an Animal Model of Alzheimer's Disease.},
journal = {Annals of neurosciences},
volume = {},
number = {},
pages = {09727531261470562},
pmid = {42774443},
issn = {0972-7531},
abstract = {BACKGROUND: Alzheimer's disease (AD) is a gradual neurodegenerative disorder presenting with cognitive and non-cognitive impairment. Currently approved therapies alleviate symptoms but do not modify disease progression and may be associated with adverse effects.

OBJECTIVE: This study aimed to compare the effect of nilotinib (a tyrosine kinase inhibitor) and N [ω]-nitro-l-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor) as agents that improve learning and memory processes in a scopolamine-induced rat model of AD with memantine.

METHODS: Thirty adult male Wistar rats were randomly assigned to five groups (n = 6 in each group). Scopolamine hydrobromide 3 mg/kg i.p. once daily for 7 days was used to induce AD-like cognitive deficits. Behavioural testing (elevated plus maze [EPM] and Morris water maze [MWM]) was performed on days 8 and 9. From day 10, rats were treated with nilotinib (10 mg/kg p.o.), L-NAME (10 mg/kg i.p.), memantine (10 mg/kg p.o.) or saline for 21 days. Behavioural testing was repeated on days 29 and 30. Then, animals were sacrificed, and brain homogenates were prepared for estimation of acetylcholinesterase (AChE), amyloid-beta 1-42 (Aβ1-42) and PARK-7 levels.

RESULTS: Scopolamine increased transfer latency in the EPM and escape latency in the MWM and increased AChE and Aβ1-42 levels, but it decreased PARK-7. Both nilotinib and L-NAME significantly reduced transfer latency and escape latency compared to scopolamine (all p < .001). Both treatments reduced AChE and Aβ1-42 levels and increased PARK-7. Nilotinib produced significantly greater improvements than L-NAME (p < .01) with effects comparable to memantine.

CONCLUSION: Nilotinib and L-NAME improved cognitive function and modulated cholinergic, amyloid and autophagy-related markers in a rat model of AD. Nilotinib demonstrated superior efficacy to L-NAME and may represent a potential therapeutic strategy for AD. Further studies are warranted to evaluate long-term effects and clinical applicability.},
}

@article {pmid42774645,
year = {2026},
author = {Ma, X and Yan, F and Liu, Z and He, S and Liu, L and Liang, J and Yuan, M and Wang, S and Qu, S and Yang, S and Gao, Y and Qiu, H and Li, Y and Yang, C and Li, Y and Li, T and Wang, Y},
title = {Bilateral Angular Gyrus 810-nm Transcranial Near-Infrared Stimulation Reshapes Brain Network: Ameliorate Alzheimer's Disease Cognitive Deficits.},
journal = {BME frontiers},
volume = {7},
number = {},
pages = {0313},
pmid = {42774645},
issn = {2765-8031},
abstract = {Objective: To investigate the clinical efficacy and neural mechanisms of targeted 810-nm transcranial near-infrared stimulation (tNIRS) over the bilateral angular gyrus in Alzheimer's disease (AD). Impact Statement: We provide the first clinical evidence that targeted tNIRS ameliorates AD cognitive deficits by dynamically reconfiguring large-scale brain networks, establishing a precise, mechanistic neuromodulation strategy. Introduction: While tNIRS shows potential for AD, conventional whole-brain irradiation lacks anatomical precision and yields inconsistent outcomes. Resolving these elusive network-level mechanisms requires targeted stimulation paradigms. Methods: In a randomized, sham-controlled trial, 36 biomarker-confirmed AD patients received 810-nm tNIRS targeted at the bilateral angular gyrus or sham stimulation (20 min/side daily, 15 d). Baseline and post-intervention neuropsychological assessments, resting-state functional magnetic resonance imaging (fMRI), and transcranial magnetic stimulation-electroencephalography (TMS-EEG) were utilized to decode cognitive improvements and network dynamics. Results: Targeted tNIRS obviously improved cognition, memory, language, attention, and executive functions while reducing neuropsychiatric symptoms. fMRI revealed enhanced intra-network connectivity within the default mode network (DMN) and promoted functional synergy between the DMN, dorsal attention, frontoparietal, and limbic networks. TMS-EEG demonstrated enhanced information flow and dynamic nodal reconfiguration, specifically boosting prefrontal and temporo-occipital activation. Conclusion: Bilateral angular gyrus targeted tNIRS may effectively mitigate AD cognitive impairment potentially through modulation of functional connectivity and adaptively reconfiguring higher-order cognitive networks, serving as a highly promising clinical neuromodulation therapy.},
}

@article {pmid42774984,
year = {2026},
author = {He, H and Habeck, CG and Stern, Y},
title = {Amyloid-beta relates to default and attention network connectivity during working memory retrieval.},
journal = {Brain communications},
volume = {8},
number = {4},
pages = {fcag278},
pmid = {42774984},
issn = {2632-1297},
abstract = {As one of the earliest pathological events in Alzheimer's disease, amyloid-beta accumulation has been linked to alterations in large-scale brain networks, especially the default mode network. While most prior work has focused on resting-state functional connectivity or task-evoked activation, how amyloid-beta relates to task-modulated connectivity that directly supports behaviour is less explored. Here, we examined the relationship between amyloid-beta burden and task-modulated connectivity during a Letter-Sternberg verbal working memory task in 84 cognitively normal older adults from an ongoing longitudinal cohort (aged 56-71 years; 41 females). To further understand these connectivity alterations, we tested whether these connections were associated with task performance or with cognitive reserve proxies. We found that higher amyloid-beta burden was associated with reduced connectivity-specifically during the probe-phase of working memory retrieval. At the regional scale, lower node strength in posterior-medial regions of the default mode network was related to worse task performance and mediated the amyloid-behaviour relationship. At the network scale, altered coupling between the default mode and dorsal attention networks was related to task performance but did not mediate the amyloid-behaviour relationship. Moreover, physical activity was associated with network-level coupling but not with regional node strength. These findings suggest that amyloid-beta burden disrupts retrieval-related working memory systems, particularly regions of the default mode network, while coupling between the default mode and dorsal attention networks is related to physical activity, a cognitive reserve proxy. Collectively, task-modulated connectivity provides insight into pathways through which early Alzheimer's disease pathology influences working memory performance and may inform targeted lifestyle or neuromodulation interventions for older adults.},
}

@article {pmid42775105,
year = {2026},
author = {Tan, G and Wang, X and Chen, J and Feng, R and Chu, H and Yang, D and Li, J and Yang, M and Huang, Y and Li, J and Gao, F},
title = {The potential of platelet-rich plasma and PRP-derived biologics for neurological disorders: mechanisms and translational research.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1858720},
pmid = {42775105},
issn = {1664-3224},
mesh = {*Platelet-Rich Plasma/metabolism ; Humans ; Animals ; Translational Research, Biomedical ; *Nervous System Diseases/therapy/metabolism ; *Biological Products/therapeutic use ; Nerve Regeneration ; },
abstract = {Platelet-rich plasma (PRP), an autologous blood derivative rich in multiple growth factors and cytokines, has shown broad application prospects in the field of tissue repair and regeneration. In recent years, the therapeutic potential of PRP in neurological disorders has gained increasing attention. This article systematically reviews the classification systems, preparation methods, and the molecular mechanisms and application progress of PRP in neural repair. In preclinical studies, PRP has been shown to release insulin-like growth factor-1 (IGF-1), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and transforming growth factor-β (TGF-β), which may synergistically activate PI3K/Akt and MAPK/ERK signaling pathways, suggesting potential tissue repair, axonal regenerative, angiogenic, and immunomodulatory effects. The three-dimensional fibrin scaffold formed upon platelet activation not only provides physical support for cell migration and axonal growth but also enables the sustained local release of growth factors. In central nervous system disorders, intrathecal PRP has shown potential in animal models to alleviate neuroinflammation after spinal cord injury(SCI), and intranasal administration can improve cognitive function and neurogenesis in Alzheimer's disease(AD) models. In peripheral nervous system disorders, local injection or PRP filling within nerve conduits significantly promotes regeneration and functional recovery after injuries to the sciatic nerve, facial nerve, and others. Furthermore, the therapeutic efficacy of PRP is influenced by factors such as preparation method, cellular composition (leukocyte content), administration route, and activation method. Although preclinical evidence is substantial, the clinical application of PRP in neurological disorders still faces challenges including a lack of standardization, unclear mechanisms, and the need to verify long-term safety. This review aims to provide a theoretical basis and practical reference for further research and clinical translation of PRP in the field of neural repair.},
}

*Platelet-Rich Plasma/metabolism
Humans
Animals
Translational Research, Biomedical
*Nervous System Diseases/therapy/metabolism
*Biological Products/therapeutic use
Nerve Regeneration

@article {pmid42775169,
year = {2026},
author = {Xue, F and Bao, L and He, A and Liang, S},
title = {CRISPR-based functional genomic screening in neurodegeneration: mechanistic insights into AD, PD, and ALS.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1831375},
pmid = {42775169},
issn = {1663-4365},
abstract = {Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are characterized by pronounced clinical and molecular heterogeneity, as well as highly interconnected pathogenic pathways. This biological complexity has long hindered efforts to systematically define disease mechanisms and to develop effective, targeted therapies. In recent years, clustered regularly interspaced short palindromic repeats (CRISPR) based functional genomic screening technologies have emerged as powerful tools for large-scale genetic perturbation in cellular, organoid, and in vivo models, enabling unbiased interrogation of disease relevant genetic networks and the identification of potential therapeutic targets. In this review, we summarize CRISPR knockout, CRISPR interference, CRISPR activation, and in vivo screening studies in AD, PD, and ALS, with emphasis on pathological phenotypes, experimental models, cell types, validation strategies, and evidence strength. In AD, these screens have identified regulators of amyloid-β (Aβ) production, Tau homeostasis and propagation, microglial states, neuronal aging, and stress responses. In PD, they have provided insights into α-synuclein (α-syn) homeostasis, mitochondrial quality control, lysosomal trafficking, and transplanted dopaminergic neuron survival. In ALS, they have identified modifiers of C9orf72-associated toxicity, repeat-associated non-AUG translation, TAR DNA-binding protein 43 (TDP-43) inclusion formation, and ATXN2 homeostasis. Cross-disease comparison indicates recurring involvement of proteostasis, endolysosomal function, mitochondrial regulation, and cellular stress responses, although individual screening hits show limited overlap and remain strongly influenced by experimental context. Overall, CRISPR-based screening provides a useful framework for identifying candidate disease modifiers, but further validation across complementary human-relevant and in vivo models is required before therapeutic translation.},
}

@article {pmid42775298,
year = {2026},
author = {Pandey, HK and Gudenkauf, KJ and Swaminathan, V},
title = {Progressive Neurodegeneration From Anoxic Injury Following Perioperative Cardiac Arrest.},
journal = {Cureus},
volume = {18},
number = {8},
pages = {e115034},
pmid = {42775298},
issn = {2168-8184},
abstract = {Severe hypoxic-ischemic brain injury following cardiac arrest can result in persistent and evolving neurologic, cognitive, and visual impairment, with later clinical decline that may be difficult to distinguish from superimposed neurodegenerative disease. A prolonged and evolving pattern of neurologic, cognitive, and visual impairment is documented in a woman throughout her 70s and 80s who survived a perioperative cardiac arrest requiring an extended resuscitation interval. Her recovery was complicated by Anton syndrome, prosopagnosia, gait apraxia, chronic microvascular disease with progressive atrophy, intermittent episodes of delirium during superimposed infections, and later neuroimaging findings suggestive of Alzheimer-type degeneration. This case illustrates the dynamic trajectory of severe anoxic encephalopathy, the challenge of differentiating delayed post-hypoxic injury from superimposed neurodegenerative disease, and the need for sustained multidisciplinary care extending well beyond the initial insult. Serial cognitive assessments over nearly a decade further demonstrate the patient's initial severe impairment, subsequent partial cognitive recovery, and later persistent moderate impairment, while the evolution of the neuroimaging raises the important question of whether the changes found represented chronic post-anoxic injury, Alzheimer's disease, or a combination of both.},
}

@article {pmid42775339,
year = {2026},
author = {Shah, SK and Xiang, L and Upchurch, GR and Adler, RR and Shah, KB and Clark, CJ and Finlayson, E and Kim, DH and Lin, KJ and Lipsitz, SR and Weissman, JS},
title = {Dementia Is Associated With Adverse Outcomes After Nonruptured Abdominal Aortic Aneurysm Repair.},
journal = {Annals of surgery open : perspectives of surgical history, education, and clinical approaches},
volume = {7},
number = {3},
pages = {e714},
pmid = {42775339},
issn = {2691-3593},
abstract = {OBJECTIVE: To compare outcomes after nonruptured abdominal aortic aneurysm (AAA) repair among Medicare beneficiaries with and without Alzheimer disease and related dementias (ADRD).

BACKGROUND: AAA repair carries substantial risks; outcomes data in patients with ADRD are extremely limited.

METHODS: We conducted a retrospective cohort study using Medicare fee-for-service claims (2016-2020) of beneficiaries ≥66 years who underwent nonruptured AAA repair. ADRD was ascertained using a validated 12-month lookback algorithm. Outcomes were 30-, 90-day, and 1-year mortality, readmissions, major inpatient complications, and discharge destination. Associations were estimated with propensity score-weighted models adjusted for age, sex, race, Elixhauser comorbidity index, claims-based frailty, and repair type (endovascular vs open).

RESULTS: Of 42,733 repairs, 1817 (4.3%) involved patients with ADRD, who were older (median 80.8 vs 75.8 years), more often female (30.7% vs 25.0%), less often non-Hispanic White (84.2% vs 90.1%), and more likely to receive endovascular repair (89.1% vs 83.8%). Unadjusted outcomes were worse across mortality, readmissions, and major complications. After adjustment, ADRD was associated with higher mortality (30-day adjusted odds ratio [aOR] 1.50, 95% confidence interval [CI] 1.15-1.95; 1-year aOR 1.83, 95% CI 1.59-2.11), greater readmissions (30-day aOR 1.26, 95% CI 1.06-1.49; 90-day aOR 1.25, 95% CI 1.07-1.45), and increased discharge to higher-level care (aOR 2.46, 95% CI 2.12-2.85).

CONCLUSIONS: In this national cohort, ADRD was associated with increased mortality, readmissions, and discharge to higher-level care after AAA repair despite more frequent use of endovascular repair.},
}

@article {pmid42775489,
year = {2026},
author = {Tan, Y and Zhang, Q and Fu, Y and Zhang, M and An, J and Liu, X and Yu, Y and Zhang, H and Yang, L and Cheng, K and Yu, Q and Fang, Y and Zhang, D},
title = {Porous Framework Materials and MXenes as Biosensing Platforms for Amyloid-β Detection.},
journal = {Chemical record (New York, N.Y.)},
volume = {},
number = {},
pages = {e70253},
doi = {10.1002/tcr.70253},
pmid = {42775489},
issn = {1528-0691},
support = {82575209//National Natural Science Foundation of China/ ; },
abstract = {Amyloid-β (Aβ), a 39-43-amino-acid peptide, is closely associated with the pathogenesis of Alzheimer's disease (AD) and undergoes abnormal aggregation that contributes to disease progression. Therefore, rapid and accurate Aβ detection is essential for early AD diagnosis and therapeutic monitoring. Biosensors have emerged as promising analytical tools owing to their simplicity, low cost, high sensitivity, and selectivity. In particular, metal-organic frameworks, covalent organic frameworks, hydrogen-bonded organic frameworks, and MXenes offer unique structural and functional advantages for Aβ sensing. This review summarizes recent advances in Aβ biosensors based on these materials, with emphasis on comparative analytical performance across electrochemical, optical, photoelectrochemical, and dual-mode platforms. Current challenges, including matrix interference, limited discrimination of Aβ isoforms, and biosensor miniaturization, are discussed. Future directions involving artificial intelligence and machine learning are also highlighted to advance rapid, sensitive, and accurate Aβ detection for early AD diagnosis and therapeutic monitoring.},
}

@article {pmid42775668,
year = {2026},
author = {Yin, Y and Li, Z},
title = {Mitochondrial Fusion and Fission in Age-Related Cardio-Cerebral Diseases: Mechanisms and Interventions.},
journal = {Aging cell},
volume = {25},
number = {10},
pages = {e70729},
doi = {10.1111/acel.70729},
pmid = {42775668},
issn = {1474-9726},
support = {2023JH2/101700204//The Science and Technology Program Joint Program of Liaoning Province (Project of Fundamental Research for Application)/ ; },
mesh = {Humans ; *Mitochondrial Dynamics/drug effects ; *Aging/metabolism/pathology ; Animals ; *Cardiovascular Diseases/metabolism/pathology ; *Cerebrovascular Disorders/metabolism/pathology ; *Mitochondria/metabolism ; },
abstract = {Mitochondria play a crucial role in cellular energy metabolism. The heart and brain require a continuous and stable energy supply. Energy production strongly depends on proper mitochondrial function. Mitochondrial fusion and fission, known as "plasticity", are vital for maintaining the normal physiological function of cells. Recent studies have shown that impaired mitochondrial dynamics are present in many aging-related diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and atherosclerotic cardio-cerebrovascular disease. The role of impaired mitochondrial dynamics in the pathophysiological process of aging-related diseases is being actively researched. We discovered that targeting proteins related to mitochondrial dynamics, especially those involved in fission and fusion, may offer new treatment strategies for these diseases. Various approaches, including aerobic interval and treadmill training and the use of drugs such as the antidiabetic agents metformin and dapagliflozin, the antihypertensive agent irbesartan, and certain traditional Chinese medicine components, have shown potential in alleviating imbalances in mitochondrial dynamics in aging-related cardio-cerebrovascular diseases. In this review, we systematically summarize recent research on alterations in mitochondrial dynamics in age-related cardio-cerebral diseases and explore therapeutic strategies targeting these alterations, which may offer new directions for improving cardiac and brain health and guiding clinical practice.},
}

Humans
*Mitochondrial Dynamics/drug effects
*Aging/metabolism/pathology
Animals
*Cardiovascular Diseases/metabolism/pathology
*Cerebrovascular Disorders/metabolism/pathology
*Mitochondria/metabolism

@article {pmid42775737,
year = {2026},
author = {Rist, PM and Li, S and Hamaya, R and Anderson, AK and Yang, T and Xu, YR and Ostaszewski, BL and Selkoe, DJ and Sesso, HD and Manson, JE},
title = {Effect of a multivitamin and cocoa flavanol extract on changes in neurofilament light, N-terminal tau fragment, and oligomeric amyloid-β levels in COSMOS-clinic.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261489739},
doi = {10.1177/13872877261489739},
pmid = {42775737},
issn = {1875-8908},
abstract = {BackgroundMultivitamin-multimineral (MVM) supplements and cocoa flavanols may delay cognitive aging, but underlying pathways remain unclear.ObjectiveWe examined the effect of MVM or cocoa extract (CE) supplementation on 2-year changes in three blood-based neurodegenerative biomarkers.MethodsThe COcoa Supplement and Multivitamin Outcomes Study (COSMOS) was a 2 × 2 factorial trial of a MVM (Centrum Silver) and/or CE supplement (containing 500 mg/d, including 80 mg (-)-epicatechin) among older US adults free of major cardiovascular disease and recently diagnosed cancer. The primary outcomes of this ancillary study were the 2-year change in neurofilament light chain (NfL), N-terminal tau fragment (NT1), and oligomeric amyloid-β (oAβ) levels. We examined the effect of each intervention on each biomarker in separate general linear models of response profiles.ResultsWe included 506 individuals with available NT1 or NfL levels and 498 individuals with oAβ levels. We observed no significant difference between the changes over time in either NT1 (mean difference in yearly percentage change=3.7%; 95% CI: -3% to 10.8%; p = 0.29), NfL (3.1%; 95% CI: -1.9% to 8.3%; p = 0.23), or oAβ (-8.9%; 95% CI: -23.9% to 9%; p = 0.31) for those randomized to MVM versus placebo. We observed no significant differences between changes over time for those randomized to CE versus placebo for NT1 (-0.7%; 95% CI: -7.1% to 6.1%; p = 0.83), NfL (0.5%; 95% CI: -4.4% to 5.6%; p = 0.85), or oAβ (-5.9%; 95% CI: -21.4% to 12.6%; p = 0.51).ConclusionsDaily supplementation with MVM or CE compared to placebo did not affect two-year changes in NfL, NT1, and oAβ.Clinicaltrials.gov: COSMOS (clinicaltrials.gov NCT02422745).},
}

@article {pmid42775775,
year = {2026},
author = {Anderson, JG and Dowling, NM and Flatt, JD},
title = {Caregiving in Alzheimer's Disease and Related Dementias: Insights from Diverse Family Structures.},
journal = {American journal of Alzheimer's disease and other dementias},
volume = {41},
number = {},
pages = {15333175261489377},
doi = {10.1177/15333175261489377},
pmid = {42775775},
issn = {1938-2731},
mesh = {Humans ; *Caregivers/psychology ; *Alzheimer Disease/nursing ; *Dementia/nursing ; Family Structure ; },
abstract = {The growing population of people living with Alzheimer's disease and related dementias (ADRD) has increased the demand for informal care by family members and friends. While a growing number of studies about ADRD caregiving have engaged caregivers from diverse racial, ethnic, and/or sexual and gender minority backgrounds, more research is needed regarding the lived experiences of these populations of caregivers and the barriers and facilitators to supporting their well-being. This special collection aimed to understand better the impact and complex dynamics of caring for someone living with ADRD within diverse family structures.},
}

Humans
*Caregivers/psychology
*Alzheimer Disease/nursing
*Dementia/nursing
Family Structure

@article {pmid42775783,
year = {2026},
author = {Yang, Y and Kwak, YT},
title = {Neuropsychiatric symptom-role reorganization in amyloid PET-positive Alzheimer's disease: An expanded-cohort analysis.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261489744},
doi = {10.1177/13872877261489744},
pmid = {42775783},
issn = {1875-8908},
abstract = {BackgroundNeuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) often occur in clusters, and their clinical meaning may depend on the symptoms with which they co-occur. Whether a previously identified NPS cluster pattern remains transportable after expansion of an amyloid PET-positive cohort is uncertain.ObjectiveTo assess the transportability of a previously published NPS cluster model and to characterize symptom-role reorganization after cohort expansion.MethodsWe analyzed 301 consecutive drug-naive patients with probable AD and positive [18]F-FC119S amyloid PET. The cohort comprised the previously published 143-patient reference cohort and 158 newly enrolled, non-overlapping patients who constituted the extension cohort. Twelve Korean Neuropsychiatric Inventory domains were coded as present or absent. Hierarchical clustering was repeated in the extension cohort and in the full cohort, and changes in individual symptom relationships were examined.ResultsThe original four-cluster solution was only partly reproduced. Aggression, disinhibition, and aberrant motor behavior remained closely grouped, while anxiety and irritability also remained linked and were joined by euphoria. Hallucination shifted into the behavioral-dyscontrol cluster, whereas depression, apathy, nighttime behavior, and eating abnormality formed a vegetative-apathy cluster. Delusion formed a single-domain cluster and, together with aggression, aberrant motor behavior, and disinhibition, showed the largest stage-associated prevalence differences between Clinical Dementia Rating (CDR) 0.5 and CDR 1.0-2.0.ConclusionsNPS clusters in amyloid PET-positive AD may not represent fixed syndromes. A symptom-role framework that distinguishes preserved relationships, reorganized symptoms, and independent stage-linked symptoms may provide a more clinically informative understanding of NPS in AD.},
}

@article {pmid42775784,
year = {2026},
author = {Arai, H and Aiba, S and Yamamoto, H and Akiba, Y and Takayama, J and Arai, R},
title = {Clinic-based real-world analysis of amyloid PET positivity and MRI markers across subjective cognitive decline, mild cognitive impairment, and early Alzheimer's disease.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261490596},
doi = {10.1177/13872877261490596},
pmid = {42775784},
issn = {1875-8908},
abstract = {BackgroundAlzheimer's disease (AD) is increasingly defined biologically. Amyloid positron emission tomography (PET) is a validated biomarker; however, evidence from truly consecutive, real-world memory-clinic cohorts spanning subjective cognitive decline (SCD), mild cognitive impairment (MCI), and early AD remains limited. Structural MRI markers such as the voxel-based specific regional analysis system for AD (VSRAD) are widely used, yet their incremental value for predicting amyloid positivity in real-world settings is uncertain.ObjectiveTo quantify amyloid PET positivity across SCD, MCI, and early AD in a real-world cohort and test whether MRI indices improve prediction beyond clinical diagnosis.MethodsWe retrospectively analyzed 194 consecutive patients undergoing [18]F-florbetapir amyloid PET (SCD n = 93; MCI n = 47; early AD n = 54). Positivity was determined by certified visual reads. Quantitation used Centiloid (CL) values retained on the original continuous scale (including negative values) and regional standardized uptake value ratios (SUVR). MRI/VSRAD indices were available in 153 patients. Logistic regression models were evaluated by cross-validated area under the curve (AUC).ResultsAmyloid PET positivity increased stepwise (SCD 40.9%, MCI 66.0%, early AD 91.7%; p < 0.0001). CL and regional SUVRs increased in parallel, most prominently in the temporal cortex and precuneus. Although VSRAD indices correlated with amyloid burden, adding MRI to the base model did not improve discrimination (AUC 0.752 versus 0.751).ConclusionsClinical utility of amyloid PET was confirmed in a real-world, consecutive memory-clinic cohort, supporting the relevance of amyloid assessment for routine practice and future clinical application.},
}

@article {pmid42775787,
year = {2026},
author = {Xu, ZJ and Ma, J and Giuffrè, GM and Wu, JJ and Xue, X and Lu, JJ and Rossini, PM and Hua, XY and Xu, JG},
title = {APOE-centered transcriptional convergence underlying diverse dementia subtypes.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261489800},
doi = {10.1177/13872877261489800},
pmid = {42775787},
issn = {1875-8908},
abstract = {BackgroundDementia subtypes exhibit diverse clinical and pathological features, yet may share convergent molecular underpinnings. Identifying these common pathways is critical for unified therapeutic strategies.ObjectiveTo delineate the shared genetic architecture and convergent molecular pathways underlying diverse dementia subtypes, and to mechanistically characterize the structural and functional impacts of key risk variants, thereby establishing a unified framework for precision therapeutic development.MethodsWe applied multivariate genomic structural equation modeling to six dementia-related genome-wide association studies (GWAS), followed by integrative transcriptome-wide association studies (TWAS) across tissues and cell types. We combined AlphaFold3-predicted structures, molecular dynamics simulations, and deep learning-based stability analyses to assess functional impacts of risk variants.ResultsWe uncovered a shared genetic architecture underlying dementia, identifying 60 novel risk loci. APOE emerged as the central hub, linking lipid metabolism and immune dysregulation. Missense variants in APOE (p.Arg176Cys), BIN2 (p.Glu190Lys), and FOXO1 (p.Asp82His/Tyr/Asn) induced charge-dependent conformational destabilization, impairing lipid transport, microglial phagocytosis, and transcriptional control.ConclusionsOur multiscale framework bridges population genetics with molecular pathophysiology, establishing APOE-centered transcriptional dysregulation as a unifying mechanism in dementia. These findings nominate convergent pathways, particularly lipid-immune crosstalk, as high-priority targets for precision therapeutics.},
}

@article {pmid42775789,
year = {2026},
author = {Zhu, Q and Chen, W and Han, X},
title = {A multi-omics Mendelian randomization study identifies putatively causal genes and pathways for Alzheimer's disease associated with reactive astrocytes.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261489741},
doi = {10.1177/13872877261489741},
pmid = {42775789},
issn = {1875-8908},
abstract = {BackgroundNeuroinflammation, particularly involving reactive astrocytes, plays a pivotal role in Alzheimer's disease (AD) progression.ObjectiveHowever, the causal genes and regulatory pathways linking astrocyte reactivity to AD risk remain unclear.MethodsWe performed a multi-omics summary-data-based Mendelian randomization (SMR) analysis, integrating large-scale AD GWAS data with methylation (mQTLs), expression (eQTLs), and protein (pQTLs) data for 514 reactive astrocyte-related genes. Causal inference was strengthened using colocalization and tissue-specific validation, and pathway enrichment.ResultsOur multi-omics SMR analysis identified a core set of high-confidence genes related to reactive astrocytes with putatively causal roles in AD. Based on mQTL-eQTL analysis, SPARC (cg08331313), RPS6KA2 (12 CpG sites), and LEP (4 CpG sites) demonstrated significant regulatory cascades, where methylation changes modulated gene expression and subsequently influenced AD risk. The eQTL-pQTL analysis revealed GCDH as genes with strong expression-protein correlations. Cross-tissue validation between blood and brain pinpointed a robust set of seven genes, including MAPK3, HLA-DQB1, and CSF3, that consistently associate with AD risk, highlighting systemic effects. Functional and network analyses of these causal candidates revealed that they converge upon the MAPK signaling pathway as a central mechanistic hub in both peripheral blood and brain tissue. Furthermore, network analysis identified seven hub genes, including MAPK3, LEP, and STAT1, as critical regulators within this astrocyte-centered AD network.ConclusionsOur study systematically identifies genetically predicted reactive astrocyte-related genes in AD pathogenesis through multi-omics Mendelian randomization, highlighting MAPK signaling as a putatively causal mechanistic hub.},
}

@article {pmid42776293,
year = {2026},
author = {Zayed, M and Mahmoud, M and Massoud, A and Darwish, R and Jeong, BH},
title = {The SLC7A11 Thermostat: A Molecular Signaling Switch Between Ferroptosis and Disulfidptosis in Neurodegenerative Disease.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42776293},
issn = {1559-1182},
support = {RS-2025-23963916//Basic Science Research Program through the National Research Foundation (NRF) of Korea/ ; RS-2025-00517133, RS-2025-24792972//Basic Science Research Program through the National Research Foundation (NRF) of Korea/ ; },
mesh = {*Disulfidptosis/physiology ; Humans ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; *Signal Transduction ; *Ferroptosis/physiology ; *Amino Acid Transport System y+/metabolism ; Models, Biological ; },
abstract = {Neurodegenerative diseases are characterized by a metabolic paradox, a balance regulated at the molecular level by a narrow set of redox-sensitive signaling checkpoints. The cystine/glutamate antiporter SLC7A11 plays a central role in this challenge. Traditionally recognized as an antioxidant guardian that prevents ferroptosis through NRF2-KEAP1-driven glutathione synthesis, SLC7A11 can become a burden under metabolic stress. Under glucose restriction or mitochondrial dysfunction, impaired NADPH regeneration prevents cells from reducing imported cystine, leading to disulfide stress in cytoskeletal actin-binding proteins and a novel form of regulated cell death called disulfidptosis. We suggest that neural cell fate and intercellular redox support depend not only on the presence of SLC7A11 activity but also on its specific calibration in each cell type, taking into account cystine availability, glutamate management, and NADPH regeneration. Since baseline system Xc[-] activity in the CNS is primarily observed in astrocytes and microglia, this regulatory mechanism may operate both within individual cells and across cell types via the astrocyte-neuron metabolic network. Within this proposed framework, insufficient SLC7A11 activity may increase ferroptotic susceptibility, whereas sustained cystine uptake under severe NADPH limitation may create conditions permissive for disulfidptosis. In Alzheimer's disease, chronic cerebral glucose hypometabolism might lead to disulfide stress in neural cells with high SLC7A11 levels, although the typical disulfidptosis process has not yet been confirmed in vivo. We argue that traditional antioxidant supplements or SLC7A11 modulation are unlikely to succeed without understanding this dual-risk profile at the level of molecular pathways. We propose shifting toward precise adjustment via biomarker-guided redox modulators and metabolic priming to enhance NADPH reserves. By examining SLC7A11 as a dynamic molecular regulator, this review offers a hypothesis-generating framework that may help resolve conflicting findings and inform the development of focused neuroprotective approaches relevant to the molecular neurobiology of neurodegenerative disease.},
}

*Disulfidptosis/physiology
Humans
*Neurodegenerative Diseases/metabolism/pathology
Animals
*Signal Transduction
*Ferroptosis/physiology
*Amino Acid Transport System y+/metabolism
Models, Biological

@article {pmid42776386,
year = {2026},
author = {Roslund, KJ and Coates, LC and Sattar Sultani, S and Hayes, D and Diaz, S and Rutkowsky, JM and Zhou, Z and Ramsey, JJ and Taha, AY and Slupsky, CM},
title = {Ketone ester supplementation in aged mice produces sex-specific cognitive and metabolic effects.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {42776386},
issn = {2509-2723},
support = {R21 AG07115601//NIH Office of the Director/ ; },
abstract = {The ketogenic diet (KD) elevates β-hydroxybutyrate (β-HB), an energy metabolite and signaling molecule with immunomodulatory effects, and has been associated with cognitive and metabolic effects in some preclinical and clinical studies. However, clinical evidence for ketogenic and ketone-based interventions in cognitive aging and Alzheimer's disease remains mixed, and long-term carbohydrate restriction may be difficult to implement in older adults. Dietary supplements that elevate β-HB, such as medium-chain triglycerides and ketone esters, have been proposed as alternatives to the KD, but their sex-specific effects in aging remain poorly defined. Here, we determined the effects of short-term supplementation with the ketone monoester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate on physical function, metabolism, and age-related memory outcomes in 24-month-old male and female C57BL/6 mice. The ketone ester-containing diet increased postprandial β-HB and lowered postprandial glucose; however, its effects on cognitive, anthropometric, inflammatory, and metabolic outcomes differed by sex. In males, the intervention changed body composition, with lower body fat and higher relative lean mass. In females, the intervention was associated with fewer Barnes maze primary errors and lower hippocampal IL-1β expression. These sex-dependent effects were accompanied by differences in fasting metabolite profiles across tissues and biofluids and by altered hippocampal oxylipins. Further studies are needed to determine whether ketone monoester supplementation has similar sex-specific effects in humans, and to define the mechanisms, physiological changes, and translational relevance of ketone-based interventions in aging.},
}

@article {pmid42776415,
year = {2026},
author = {Maeshiba, M and Kajiya, H and Migita, K and Goto-T, K and Seki, T and Tsuzuki, T},
title = {Restoration of Normal Occlusion Suppresses the Risk of Dementia.},
journal = {Neurochemical research},
volume = {51},
number = {5},
pages = {},
pmid = {42776415},
issn = {1573-6903},
mesh = {Animals ; Mice, Transgenic ; Mice ; Hippocampus/metabolism/pathology ; *Alzheimer Disease/prevention & control/metabolism/genetics ; *Dementia/prevention & control/metabolism ; tau Proteins/metabolism ; Male ; Amyloid beta-Peptides/metabolism ; *Dental Occlusion ; Amyloid beta-Protein Precursor/genetics ; Mice, Inbred C57BL ; },
abstract = {Tooth loss is associated with a progressive decline in cognitive ability. Although occlusal support after tooth loss using dentures may reverse this effect, the underlying mechanisms are unclear, hampering improved evidence-based dentistry for at-risk patients. The current experiments examined the associations of tooth loss and restoration of occlusal support with neuropathology and cognitive decline in a mice model of Alzheimer's disease (AD). A triple-mutant knock-in mouse model of AD (App[NL-G-F] mice), and a single-mutant knock-in control line, (App[NL] mice), were divided into three subgroups: untreated, molar extraction at 6 weeks of age, and molar extraction with occlusal support. Animals were examined before occlusal support at 2, 4, and 6 months and after occlusal support at 3, 5, and 7 months of age. We designated 2-3, 4-5, and 6-7 months as the early, middle, and late stages. Cognitive functions were assessed using the 8-arm radial maze test and novel object recognition test, while accumulation or altered expression levels of AD-associated molecules were measured in hippocampus. The App [NL-G-F]mice and App[NL] mice groups showed significant cognitive decline and increased accumulation of Aβ and phosphorylated Tau in the hippocampus during the early and middle stages. Restoring normal occlusal support suppressed the upregulation of AD-related molecules, including Aβ, phosphorylated Tau, and interleukin-1β in App [NL-G-F] mice during the early and middle stages. Restoration of normal occlusal support can mitigate the risk factors of dementia, potentially by reducing neuroinflammation and thereby reversing Aβ and phosphorylated Tau accumulation.},
}

Animals
Mice, Transgenic
Mice
Hippocampus/metabolism/pathology
*Alzheimer Disease/prevention & control/metabolism/genetics
*Dementia/prevention & control/metabolism
tau Proteins/metabolism
Male
Amyloid beta-Peptides/metabolism
*Dental Occlusion
Amyloid beta-Protein Precursor/genetics
Mice, Inbred C57BL

@article {pmid42776666,
year = {2026},
author = {Xiao, R and Quan, T and Wu, X and Xu, G and Chen, S},
title = {Weakly Supervised MRI-Based Classification of Alzheimer's Disease Using Clinical Pseudo-Labels.},
journal = {NeuroSci},
volume = {7},
number = {5},
pages = {},
doi = {10.3390/neurosci7050094},
pmid = {42776666},
issn = {2673-4087},
support = {61890951//National Natural Science Foundation of China/ ; },
abstract = {Alzheimer's disease (AD) classification from structural magnetic resonance imaging (MRI) may benefit from weak supervision that uses clinically meaningful but imperfect supervisory signals. We evaluated a weakly supervised framework in which a multilayer perceptron (MLP) trained on age, sex, and Mini-Mental State Examination (MMSE) scores generated clinical pseudo-labels to initialize a patch-based fully convolutional network (FCN). For 260 Alzheimer's Disease Neuroimaging Initiative (ADNI) training participants, subsequent refinement combined 80% of the preceding MRI-model probability with 20% of the participant's ground-truth diagnostic label. This design preserves a dominant pseudo-label/self-training component while using partial diagnostic guidance to stabilize refinement. The FCN generated whole-brain probability maps, and selected voxel probabilities were classified by a second MLP. The framework was developed using ADNI (n = 417). Using ADNI validation data only, iteration 3 and a classification threshold of 0.5 were selected and then applied unchanged to the held-out ADNI test set and the external AIBL (n = 182), FHS (n = 102), and NACC (n = 265) cohorts. The selected model achieved F1 scores of 0.853 in ADNI, 0.707 in AIBL, 0.765 in FHS, and 0.807 in NACC. These results support the feasibility and cross-cohort transferability of clinical pseudo-label-based weak supervision for MRI classification. The framework is not intended to be label-free; rather, it provides a transparent strategy for integrating imperfect clinical pseudo-labels with partially weighted diagnostic guidance during training.},
}

@article {pmid42776709,
year = {2026},
author = {Goodwin, AM and Makhnevich, A and Davidson, KW and Sinvani, L and Butler, MJ},
title = {Behavioral Interventions to Increase Physical Activity Among Dementia Caregivers: A Narrative Review of Behavior Theory, Behavior Change Techniques, and Mechanisms of Behavior Change.},
journal = {Geriatrics (Basel, Switzerland)},
volume = {11},
number = {5},
pages = {},
doi = {10.3390/geriatrics11050120},
pmid = {42776709},
issn = {2308-3417},
support = {P30AG063786/AG/NIA NIH HHS/United States ; },
abstract = {Background: Due to the rise in Alzheimer disease (AD) and AD-related dementias (AD/ADRD) in an aging population, millions of caregivers will be at risk for physical and mental health decline. As those they care for already have physical and cognitive impairment, it is crucial that caregivers maintain health-promoting behaviors. Because regular physical activity (PA) prevents functional loss and improves physical health and well-being, understanding how to help caregivers adopt and sustain PA despite unique time, caregiving, and self-efficacy barriers is a pressing public-health priority. Existing health-promoting interventions among dementia caregivers, including PA, have demonstrated limited success. To overcome the fragmentation and slow synthesis of behavioral science evidence, the Human Behavior-Change Project advocates theoretical grounding, systematic mapping of intervention components (e.g., behavior change techniques [BCTs]) using standardized taxonomies, and explicit specification of mechanisms of behavior change (MoBCs). Objective: To examine the limited success of health-promotion interventions among dementia caregivers we aimed to conduct a narrative review to synthesize evidence from interventions that evaluated PA in dementia caregivers across three domains: (1) use of behavioral theory to inform intervention design, (2) specification of BCTs, and (3) identification and measurement of MoBCs. Methods: Two scientific databases were searched to identify representative studies and reviews, using key terms including "physical activity", "intervention", "dementia", and "caregiver" from inception to July 2025. Results: Seven primary intervention trials and six reviews were selected for inclusion. Gaps across the domains were identified to inform priority areas for future research. Conclusions: There is a need to develop tailored, theory-driven PA interventions that target empirically supported BCTs and MoBCs to improve dementia caregivers' health and well-being.},
}

@article {pmid42776725,
year = {2026},
author = {Alkam, T and Tarshizi, E and Van Benschoten, AH},
title = {Nonlinear Association of Length of Stay with In-Hospital Mortality in Alzheimer's Disease Hospitalizations: Admission-Only vs. Inpatient-Course Prediction Using Explainable Machine Learning.},
journal = {Geriatrics (Basel, Switzerland)},
volume = {11},
number = {5},
pages = {},
doi = {10.3390/geriatrics11050136},
pmid = {42776725},
issn = {2308-3417},
abstract = {Background: Hospitalizations among patients with Alzheimer's disease (AD) carry substantial mortality risk, but length of stay (LOS) is time-dependent and may reflect heterogeneous inpatient trajectories. We examined unadjusted and adjusted LOS-mortality patterns and compared admission-only versus inpatient-course prediction using explainable machine learning. Methods: Using the full 2017 Nationwide Readmissions Database (NRD), we identified hospitalizations among adults aged ≥60 years with an ICD-10-CM G30.x AD code in any diagnosis position. Records with missing in-hospital mortality status were excluded. LOS was summarized in clinically interpretable bins and modeled using restricted cubic splines. Model A excluded explicit inpatient-course measures, whereas Model B added LOS, procedure count, and total charges. Performance was evaluated using patient-grouped 5-fold out-of-fold validation and summarized by AUROC and AUPRC; SHAP was used for interpretation. Results: Among 249,507 AD hospitalizations, 12,666 in-hospital deaths occurred (5.08%; weighted mortality 4.97%). Unadjusted mortality was highest at LOS 0-1 day (13.00%), lowest at 4-6 days (3.47%), and increased to 7.77% at ≥22 days. After multivariable adjustment, LOS remained strongly nonlinear, but adjusted predicted mortality declined across the modeled LOS range. Model A achieved AUROC/AUPRC of 0.780/0.180, whereas Model B improved to 0.828/0.329. Sepsis, diagnostic burden, acute kidney injury, age, stroke, and pneumonia were stable predictors; LOS and procedure burden added prognostic information in Model B. Conclusions: The crude LOS-mortality pattern was U-shaped, whereas the adjusted pattern suggests that the late-stay increase in unadjusted mortality is partly explained by patient complexity and evolving inpatient-course factors. Admission-only prediction provides meaningful early risk stratification, while inpatient-course information improves prognostic assessment as hospitalization evolves.},
}

@article {pmid42764825,
year = {2026},
author = {Chen, HW},
title = {Operator-Driven Active Craniospinal Tensioning (ACT) Device for Non-ambulatory Application.},
journal = {Cureus},
volume = {18},
number = {8},
pages = {e114854},
pmid = {42764825},
issn = {2168-8184},
abstract = {Active craniospinal tensioning (ACT) is an upright-posture axial spinal traction maneuver hypothesized to couple two mechanisms: dural pull-recoil, a cerebrospinal fluid (CSF) pressure-gradient effect shared with the supine technique pelvis-stabilized axial spinal traction (PSAST), and suboccipital venous occlusion-rebound, proposed to promote central nervous system (CNS) venous and lymphatic drainage, and as a distinct modality for cerebral venous preconditioning (CVPC). The CVPC mechanism depends on upright posture. In the upright position, cerebral venous return preferentially routes through the suboccipital venous plexus rather than the internal jugular veins, allowing the ACT strap to transiently occlude this outflow pathway during the hold and produce a hemodynamic rebound upon release. This CVPC-based rationale for choosing ACT over PSAST, along with the full biomechanical model, was developed in prior papers and is not re-derived here. In its originally described form, ACT is participant-driven: the participant voluntarily squats against a fixed overhead strap secured by a simple anchor, and the participant's own hands close the strap loop as a fail-safe. This report refers to that form, and the strap-and-anchor apparatus that delivers it, as active craniospinal tensioning, self-administered (ACT-SA). ACT-SA's delivered craniocervical junction (CCJ) tension depends on the participant fully relaxing into the maneuver. It categorically excludes non-ambulatory participants with advanced neurodegenerative disease, e.g., Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), who cannot generate or safely control a voluntary squat, yet who may stand to benefit most from craniospinal tensioning and CVPC given their disease-associated glymphatic impairment. This report describes active craniospinal tensioning, operator-driven (ACT-OD), a device that reproduces ACT-SA's anchor geometry, target force range, and hold duration while substituting the source of tensioning force. Rather than gravity acting on a squatting participant's own body mass, tension is generated by a practitioner operating a pulley-and-lever mechanism against a stationary, seated participant, with the strap confined near the forehead by a polyvinyl chloride (PVC) pipe rather than closed by the participant's own hands. Because the participant does nothing and the seated default state carries no CCJ tension, the fail-safe ACT-SA requirement becomes unnecessary; disengagement, not engagement, is ACT-OD's default. Freed from managing the strap, the practitioner can devote full attention to the lever and to continuous observation of the participant's response, a substitution that matters because non-verbal or cognitively impaired participants cannot reliably self-report the presyncopal symptoms that serve as ACT-SA's real-time safety signal. The design is offered without patent restrictions for research and clinical replication. This report presents device design and mechanism only, with no clinical outcome or efficacy data.},
}

@article {pmid42764861,
year = {2026},
author = {Qin, F and Zhang, N and Jiang, Y and Xu, K and Xiong, Y and Liu, Y and Ouyang, Q and Liu, H and Dai, Y and Jiang, L and Zhao, Y and Li, H and Wang, L and Chen, Y and Hu, L and Bu, Q and Zhao, Y and Kuang, W and Qin, M and Cen, X},
title = {Neutrophil-mediated BDNF delivery for the treatment of moderate to severe Alzheimer's disease.},
journal = {Acta pharmaceutica Sinica. B},
volume = {16},
number = {9},
pages = {6185-6202},
pmid = {42764861},
issn = {2211-3835},
abstract = {Alzheimer's disease (AD), especially its moderate-to-severe stage (MSAD), remains a global health challenge with no disease-modifying therapies. Here, we identified a dual pathological signature in MSAD patients and murine models: a systemic pro-inflammatory milieu and critically reduced brain-derived neurotrophic factor (BDNF) levels in both the hippocampus and serum. To mitigate the decrease in BDNF, we developed an engineered neutrophil capsule, in which neutrophils carrying lipid nanoparticles encapsulating BDNF penetrated the brain and ameliorated cognitive capacity deficits in MSAD mice. The pro-inflammatory state in the MSAD brain facilitated neutrophil passage through the blood-brain barrier, and inflammatory mediators triggered the release of BDNF from the engineered neutrophils. Collectively, our findings show that engineered neutrophil-mediated brain delivery of BDNF efficiently reduces the amyloid-β plaque deposition in the hippocampus, leading to significantly improved learning and memory in MSAD mice. This study establishes neutrophil-mediated delivery as a paradigm strategy for MSAD, merging cell biology with nanotechnology to reverse neurodegeneration.},
}

@article {pmid42764944,
year = {2026},
author = {Heidarian, S and Faizi, M and Alemi, M and Garmabdari, A and Nikray, N and Khoramjouy, M and Hajimahdi, Z and Zarghi, A},
title = {Design, Synthesis, Molecular Dynamics Analysis, and Biological Evaluation of New Urea Derivatives in an Animal Model of Alzheimer Disease.},
journal = {Iranian journal of pharmaceutical research : IJPR},
volume = {25},
number = {1},
pages = {e172672},
pmid = {42764944},
issn = {1726-6890},
abstract = {BACKGROUND: Alzheimer disease (AD), first described by Alois Alzheimer more than a century ago, remains a major global health challenge. Glycogen synthase kinase-3β (GSK-3β) plays an important role in AD pathophysiology. Dysregulation of GSK-3β is associated with beta-amyloid accumulation, tau hyperphosphorylation, neurodegeneration, and cognitive impairment.

OBJECTIVES: This study aimed to design and synthesize 17 arylalkyl urea derivatives as GSK-3β inhibitors and evaluate them in an animal model of AD.

METHODS: New arylalkyl derivatives were designed on the basis of the pharmacophores of GSK-3β inhibitors. Molecular docking and molecular dynamics simulations were used to evaluate the interactions of the designed compounds within the ATP-binding pocket of GSK-3β. The compounds were then synthesized by reacting substituted anilines with benzyl isocyanate, and their structures were confirmed by infrared spectroscopy, nuclear magnetic resonance spectroscopy, and liquid chromatography-mass spectrometry. The radial arm water maze was used to assess the effects of a selected compound on learning and memory deficits in an intracerebroventricular streptozotocin-induced rat model of sporadic Alzheimer-like disease.

RESULTS: Structure-activity relationship analysis indicated that variations in the R1 and R2 substituents played a crucial role in modulating GSK-3β inhibitory activity. Docking studies demonstrated that all novel derivatives fit well within the active site, with Val135 and Lys85 contributing prominently to ligand stabilization. On the basis of the docking results, compound 3b was selected for behavioural testing. Compound 3b significantly ameliorated spatial learning and memory deficits in a rat model of AD.

CONCLUSIONS: Compound 3b emerged as a promising lead in this series, combining favorable GSK-3β binding properties with robust cognition-enhancing effects in vivo. These findings may inform therapeutic design, clinical translation, and strategic development in the evolving field of AD drug discovery.},
}

@article {pmid42764999,
year = {2026},
author = {D'Amelio, C and Autelitano, S and Natale, F and Rinaudo, M and Fusco, S and Grassi, C},
title = {Differences in retroactive interference response reveal sex-specific memory resilience in pre-symptomatic triple transgenic Alzheimer's disease mice.},
journal = {Brain communications},
volume = {8},
number = {5},
pages = {fcag345},
pmid = {42764999},
issn = {2632-1297},
abstract = {Alzheimer's disease is a neurodegenerative disorder characterized by memory loss dependent on hippocampal and parahippocampal cortex dysfunction. However, recent evidence shows that patients with mild cognitive impairment progressing to Alzheimer's disease can exhibit early symptoms when assessed with more nuanced memory tests, such as those evaluating memory vulnerability to interference. Here, we characterize how sex and genotype shape the response to retroactive interference in triple-transgenic Alzheimer's disease mice at an early stage of the phenotype, when overt memory deficits are not yet present. Wild-type females were the only group resisting interference: transgenic females failed to discriminate despite normal recognition memory, irrespective of the moment during which retroactive interference was experienced, and males of both genotypes were similarly impaired at every time point tested. Both context change and increased memory strength restored discrimination in transgenic females and wild-type males, suggesting that their susceptibility depends on overlapping hippocampal representations. Transgenic males, by contrast, remained impaired when interference occurred in a different context and showed only a limited improvement after multiple training, pointing to a larger contribution of interference-induced memory decay. Overall, our data characterize the response to retroactive interference as a sex-dependent behavioural readout of early memory instability in a preclinical model of Alzheimer's disease.},
}

@article {pmid42765029,
year = {2026},
author = {Hyun, J and Jung, S and Noh, Y and Cho, Y and Saido, TC and Nah, J and Kim, KW and Jung, YK},
title = {eNAMPT-IFITM3 axis links neuroinflammation to γ-secretase activation.},
journal = {iScience},
volume = {29},
number = {10},
pages = {117496},
pmid = {42765029},
issn = {2589-0042},
abstract = {Amyloid-β (Aβ) accumulation and neuroinflammation are central features of Alzheimer's disease (AD), yet the molecular link connecting inflammatory signaling to γ-secretase activation remains poorly understood. Here, using a cell-based gain-of-function screen with a cDNA library, we identify nicotinamide phosphoribosyltransferase (NAMPT) as a positive regulator of γ-secretase activity. We demonstrate that extracellular NAMPT (eNAMPT) acts as a paracrine factor binding to cell-surface interferon-induced transmembrane protein 3 (IFITM3), enhancing its protein stability and promoting γ-secretase complex assembly to heighten amyloidogenic processing, independently of its NAD+ biosynthetic function. Pathologically, NAMPT levels are elevated in patients with AD and mouse models. Furthermore, systemic inflammation induced by lipopolysaccharide (LPS) enhances NAMPT expression and promotes the NAMPT-IFITM3 interaction and γ-secretase complex assembly in vivo, whereas NAMPT neutralization with an antibody suppresses LPS-induced γ-secretase activation. These findings establish the eNAMPT-IFITM3 axis as a key molecular link bridging neuroinflammation and γ-secretase-mediated AD pathology.},
}

@article {pmid42765175,
year = {2026},
author = {Liu, H and Yin, Z and Ye, Z and Xu, H},
title = {Identification of Gene Signatures and Molecular Mechanisms Underlying the Comorbidity of Alzheimer's Disease and Crohn's Disease Using Machine Learning.},
journal = {Psychiatry investigation},
volume = {},
number = {},
pages = {},
doi = {10.30773/pi.2026.0214},
pmid = {42765175},
issn = {1738-3684},
abstract = {OBJECTIVE: Alzheimer's disease (AD) and Crohn's disease (CD) both involve inflammation and immune dysregulation, yet the potential molecular mechanisms underlying their comorbidity remain unclear.

METHODS: We integrated transcriptomic data from AD and CD patients and applied differential expression analysis, weighted gene coexpression network analysis, protein-protein interaction networks, and multiple machine learning approaches to identify key comorbidity genes. Functional enrichment, single-cell sequencing validation, and virtual knockout analyses were used to explore their biological roles. Molecular docking was performed to evaluate the binding affinity of candidate small-molecule drugs to the identified core genes.

RESULTS: CXCL1 and IGFBP5 were identified as core comorbidity genes. CXCL1 was associated with inflammatory signaling, including cytokine receptor binding, neutrophil migration, and NOD-like receptor signaling. IGFBP5 was linked to growth factor binding, smooth muscle cell proliferation, and extracellular matrix-receptor interactions. Single-cell and virtual knockout analyses indicated that these genes play pivotal roles in inflammation, immune regulation, cell migration, and tissue remodeling, potentially bridging central and peripheral inflammation via the gut-brain axis and IgSF CAM signaling. Candidate drug prediction and molecular docking suggested that small molecules such as Dasatinib, Mifepristone, and Retinoic acid may modulate these pathways.

CONCLUSION: This study reveals the critical roles of CXCL1 and IGFBP5 in AD-CD comorbidity, providing a theoretical basis for exploring gut-brain axis mechanisms and potential targeted interventions.},
}

@article {pmid42765448,
year = {2026},
author = {Koychev, I and Rowe, JB and Amin, J and Arsland, D and Archer, H and Barber, R and Burns, A and Coulthard, E and Deasy, C and Dunne, R and Fox, N and Humphrey, SH and Jenkinson, J and Jones, D and Kennelly, S and Khan, F and Krishnan, MSP and Malhotra, P and McFarlane, B and McGuinness, B and Mummery, C and Pennington, C and Perry, JR and Raczek, G and Rasmussen, J and Ritchie, C and Taylor, JP and Underwood, BR and Venkataraman, AV and Raymont, V},
title = {Interpreting Evolving Evidence in Alzheimer's Disease: Implications for Dementia Clincians - CORRIGENDUM.},
journal = {The British journal of psychiatry : the journal of mental science},
volume = {},
number = {},
pages = {1},
doi = {10.1192/bjp.2026.10807},
pmid = {42765448},
issn = {1472-1465},
}

@article {pmid42765453,
year = {2026},
author = {van Wetering, J and van Ingen, MM and Timmermans, E and In't Veld, SGJG and Berendse, HW and Teunissen, CE and van de Berg, WDJ},
title = {Lysosomal Expression Profile in Plasma Associates with Disease Severity in Parkinson's Disease.},
journal = {Movement disorders : official journal of the Movement Disorder Society},
volume = {},
number = {},
pages = {},
doi = {10.1002/mds.70542},
pmid = {42765453},
issn = {1531-8257},
support = {//Stichting Woelse Waard/ ; grant P30 AG066515//Stanford Alzheimer's Disease Research Center NIH/NIA/ ; },
abstract = {BACKGROUND: Parkinson's disease (PD) is a clinically and biologically heterogeneous neurodegenerative disorder, driven by multiple mechanisms among which are lysosomal and mitochondrial dysfunction. Here, we explored blood-based lysosomal and mitochondrial profiles in relation to PD diagnosis and severity.

METHODS: Plasma samples (n = 504) were analyzed using SomaScan, targeting 394 lysosomal and 502 mitochondrial proteins in a discovery (ProPARK: 145 PD, 73 controls) and a validation cohort (Alzheimer's Disease Research Center [ADRC]: 104 PD, 182 controls). Linear and LASSO regression were included to compare groups and select PD-predictive proteins. Associations with Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr, Montreal Cognitive Assessment (MoCA), levodopa equivalent daily dose (LEDD) and disease duration were assessed and age-, sex-, and false discovery rate (FDR)-adjusted.

RESULTS: In ProPARK, 29 dysregulated lysosomal and 46 mitochondrial proteins were identified in PD; upregulated lysosomal sulfatase-modifying factor 1 (SUMF1) (FC = 1.41) and arrestin domain containing 3 (ARRDC3) (1.36) survived correction. LASSO identified eight lysosomal proteins (area under the curve [AUC] train: 0.83, test: 0.75) and two mitochondrial proteins (AUC train: 0.66, test: 0.65). Lysosomal score associated with disease duration, LEDD, and UPDRS-IV, whereas mitochondrial score did not. SUMF1 associated with disease duration, LEDD, and UPDRS-IV; ARRDC3 only with disease duration. In ADRC, upregulation of SUMF1 and ARRDC3 in PD (FC = 1.72 and 1.36), their association with LEDD, discriminatory AUCs of lysosomal and mitochondrial scores (0.80 and 0.58), and the association between lysosomal score and LEDD replicated.

CONCLUSIONS: Lysosomal expression scores discriminated PD from controls and associated with disease severity. SUMF1 and ARRDC3 emerged as blood-based biomarkers for PD. These findings support the use of pathway-specific biomarkers for improving PD diagnostics and monitoring disease progression. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.},
}

@article {pmid42765733,
year = {2026},
author = {Sheng, F and Yu, JM and Yang, Q and Jipei, R and Xie, WQ and Zhan, G and Zhang, Y and Zhang, LL},
title = {Integrating network pharmacology and experimental validation to uncover the mechanisms of Ganoderma lucidum in ameliorating neuroinflammation in Alzheimer's disease.},
journal = {The Journal of pharmacy and pharmacology},
volume = {78},
number = {9},
pages = {},
doi = {10.1093/jpp/rgag105},
pmid = {42765733},
issn = {2042-7158},
support = {82675242//National Natural Science Foundation of China/ ; 82304749//National Natural Science Foundation of China/ ; 82204728//National Natural Science Foundation of China/ ; SKLTCM202506//Open Research Project of Chinese Medicine Germplasm Resources Innovation and Effective Uses Key Laboratory of Sichuan Province/ ; },
mesh = {Animals ; *Reishi/chemistry ; *Alzheimer Disease/drug therapy/metabolism ; Mice ; Janus Kinase 2/metabolism ; Amyloid beta-Peptides/metabolism ; STAT1 Transcription Factor/metabolism ; *Neuroprotective Agents/pharmacology ; Molecular Docking Simulation ; Network Pharmacology ; *Neuroinflammatory Diseases/drug therapy/metabolism ; Male ; *Anti-Inflammatory Agents/pharmacology ; Hippocampus/drug effects/metabolism ; Disease Models, Animal ; Microglia/drug effects/metabolism ; Macrophages/drug effects/metabolism ; Peptide Fragments/metabolism ; Molecular Dynamics Simulation ; Signal Transduction/drug effects ; },
abstract = {OBJECTIVES: This study aimed to explore the anti-neuroinflammatory mechanism of Ganoderma lucidum against Alzheimer's disease (AD) using network pharmacology and molecular docking, and verify its neuroprotective and anti-neuroinflammatory effects in Aβ1-42-induced AD mice.

METHODS: Common targets were screened and analyzed by KEGG/GO enrichment. Core targets were evaluated by molecular docking and dynamics simulation. Aβ1-42-induced AD mice and LPS-stimulated macrophages were used. Cognitive function, Aβ deposition, tau phosphorylation, and inflammatory gene expression were measured.

KEY FINDINGS: Network analysis highlighted inflammation-related pathways. Molecular dynamics simulations confirmed stable binding between active components and targets like STAT1, STAT3, JAK2, and TNF. In vivo, G. lucidum extract suppressed abnormal activation of microglia and astrocytes, and reduced pro-inflammatory factors. Following G. lucidum administration, mRNA levels of Jak2 and Stat1 in hippocampal tissue were significantly reduced, suggesting potential regulation of neuroinflammation via the JAK2/STAT1 pathway. Concurrently, G. lucidum down-regulated transcription of key subunits (Ncstn, Aph-1, Pen-2) in the γ-secretase complex, thereby reducing Aβ1-42 production. In vitro experiments similarly confirmed G. lucidum's ability to inhibit LPS-induced IL-6 and TNF-α release from macrophages.

CONCLUSIONS: Ganoderma lucidum extract alleviates neuroinflammation in AD models, providing experimental evidence for its potential application in AD prevention or therapy.},
}

Animals
*Reishi/chemistry
*Alzheimer Disease/drug therapy/metabolism
Mice
Janus Kinase 2/metabolism
Amyloid beta-Peptides/metabolism
STAT1 Transcription Factor/metabolism
*Neuroprotective Agents/pharmacology
Molecular Docking Simulation
Network Pharmacology
*Neuroinflammatory Diseases/drug therapy/metabolism
Male
*Anti-Inflammatory Agents/pharmacology
Hippocampus/drug effects/metabolism
Disease Models, Animal
Microglia/drug effects/metabolism
Macrophages/drug effects/metabolism
Peptide Fragments/metabolism
Molecular Dynamics Simulation
Signal Transduction/drug effects

@article {pmid42766035,
year = {2026},
author = {Nabizadeh, A and Rafati, A and Karbalaei, N and Namavar, MR and Hosseinzadeh, S and Jahromi, HM and Rahimi, A and Naseh, M},
title = {Correction: Probiotic effects on cognitive performance, hippocampal oxidative stress, and structural damage induced by icv STZ in Alzheimer-like rat model.},
journal = {Brain structure & function},
volume = {231},
number = {8},
pages = {},
doi = {10.1007/s00429-026-03195-5},
pmid = {42766035},
issn = {1863-2661},
}

@article {pmid42766053,
year = {2026},
author = {Gualco, L and Montobbio, N and Losa, M and Costagli, M and Massa, F and Orso, B and Argenti, L and Peira, E and Chincarini, A and Morbelli, S and Raffa, S and Sofia, L and Sambuceti, G and Lorenzini, L and Pravatà, E and Caulo, M and Pulze, M and Arnaldi, D and Diociasi, A and Zacà, D and Piredda, GF and Hilbert, T and Kober, T and Bozzali, M and Sormani, MP and Pardini, M and Roccatagliata, L},
title = {T1 mapping in Alzheimer's disease: a quantitative MRI study with amyloid-PET correlation.},
journal = {European radiology experimental},
volume = {10},
number = {1},
pages = {},
pmid = {42766053},
issn = {2509-9280},
support = {PNRR-MCNT2-2023-12377527 - CUP C13C23001070006//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; },
mesh = {Humans ; *Alzheimer Disease/diagnostic imaging ; Female ; *Positron-Emission Tomography/methods ; *Magnetic Resonance Imaging/methods ; Aged ; Male ; Retrospective Studies ; *Amyloid/metabolism ; Cognitive Dysfunction/diagnostic imaging ; Aged, 80 and over ; },
abstract = {OBJECTIVES: Quantitative T1 mapping (qT1) is a magnetic resonance imaging (MRI) biomarker of brain microstructural changes; however, its application in Alzheimer disease (AD) remains limited. We compared cortico-limbic qT1 values between patients with AD and healthy controls (HCs) and examined their relationship with amyloid burden measured by amyloid-positron emission tomography (PET).

MATERIALS AND METHODS: We retrospectively identified subjects with mild cognitive impairment due to AD and HCs who underwent 3-T MRI, including a compressed-sensing MP2RAGE sequence, generating three-dimensional T1-weighted images and qT1 maps. Amyloid-PET was available for 16 patients. Hippocampal qT1 and volume were compared between groups, adjusting for age and sex; analyses were repeated after stratifying patients by Mini-Mental State Examination (MMSE). Voxel-wise group comparison was performed using SPM 12. The qT1-standardized uptake value ratio (SUVr) association was assessed with a linear mixed-effects model applied to voxel-level data, accounting for partial volume effects.

RESULTS: Thirty-three AD subjects, aged 69.3 ± 8.2 years (mean ± standard deviation), 18 females, and 22 HCs aged 70.5 ± 13.3 years, 15 females, were evaluated. Regional hippocampal qT1 was higher in AD (1,398 ± 53.0 ms versus 1,349 ± 53.4 ms; p = 0.002), without difference across cognitive subgroups stratified by MMSE. AD subjects exhibited increased qT1 in mesial temporal gray matter and temporo-parieto-occipital cortices (1,448 ± 55.7 ms versus 1,344 ± 51.6 ms; p < 0.001). Voxel-level modelling revealed a positive association between qT1 and amyloid-PET SUVr (p < 0.001; d = 0.223).

CONCLUSION: qT1 mapping can be sensitive to changes related to brain amyloidosis, supporting its role as a promising, noninvasive imaging biomarker in AD.

KEY POINTS: Question Can qT1 mapping detect AD-related microstructural changes in the cortico-limbic gray matter? Findings Participants with AD showed increased cortico-limbic qT1 values. A subtle yet consistent positive association was observed between cortical qT1 values and amyloid-PET SUVr. Relevance statement qT1 mapping captures microstructural tissue alterations related to amyloid pathology in Alzheimer's disease, supporting its role as a potential non-invasive imaging biomarker in this condition.},
}

Humans
*Alzheimer Disease/diagnostic imaging
Female
*Positron-Emission Tomography/methods
*Magnetic Resonance Imaging/methods
Aged
Male
Retrospective Studies
*Amyloid/metabolism
Cognitive Dysfunction/diagnostic imaging
Aged, 80 and over

@article {pmid42766082,
year = {2026},
author = {Reyes-Bueno, JA and Paredes-Pacheco, J and Muñoz-García, JB and Alfaro-Rubio, F and Ramos-Rodríguez, JR and Ariza, MJ and Rioja, J and García-Arnés, JA and García-Casares, N},
title = {White matter microstructural alterations associated with type-2 diabetes mellitus and mild cognitive impairment.},
journal = {Brain imaging and behavior},
volume = {20},
number = {5},
pages = {},
pmid = {42766082},
issn = {1931-7565},
support = {19/01375//Instituto de Salud Carlos III/ ; },
mesh = {Humans ; *Diabetes Mellitus, Type 2/diagnostic imaging/complications/psychology/pathology ; Female ; *Cognitive Dysfunction/diagnostic imaging/psychology/pathology ; Male ; Cross-Sectional Studies ; *White Matter/diagnostic imaging/pathology ; Neuropsychological Tests ; Aged ; *Brain/diagnostic imaging/pathology ; Middle Aged ; Diffusion Tensor Imaging ; Magnetic Resonance Imaging ; Anisotropy ; },
abstract = {Diabetes is one of the main risk factors for developing amnesic mild cognitive impairment and Alzheimer's disease. Several studies have found differences between the microstructural abnormalities that appear in the brains of patients with type 2 diabetes and amnesic mild cognitive impairment (T2DM-aMCI). To compare the microstructural differences between the brains of subjects with T2DM-aMCI and the brains of healthy controls. In addition, to correlate the cognitive decline of subjects with T2DM-aMCI with microstructural alterations. A cross-sectional study was conducted with a sample size of 54 patients. The participants were divided into two groups: T2DM-aMCI and healthy controls. All the participants underwent a wide range of neuropsychological tests assessing different cognitive domains. 47 subjects had MRI session. An exploratory analysis showed that the T2DM-aMCI group had a reduced fractional anisotropy in the white matter compared to the healthy controls group (p < 0.15). The most affected areas were the body of the corpus callosum and the right and left superior corona radiata. T2DM-aMCI had significant positive correlations (p < 0.05) between cerebral regions and Mini Mental State Examination, Montreal Cognitive Assessment, Rey Auditory Verbal Learning Test immediate recall and recognition, Verbal Fluency Test total words and animals. Persons with T2DM-aMCI showed less cerebral white matter integrity in different brain areas when compared to healthy controls. Positive correlations between white matter microstructural alterations and functional cognition (general cognition, memory and language) in T2DM-aMCI group were found.},
}

Humans
*Diabetes Mellitus, Type 2/diagnostic imaging/complications/psychology/pathology
Female
*Cognitive Dysfunction/diagnostic imaging/psychology/pathology
Male
Cross-Sectional Studies
*White Matter/diagnostic imaging/pathology
Neuropsychological Tests
Aged
*Brain/diagnostic imaging/pathology
Middle Aged
Diffusion Tensor Imaging
Magnetic Resonance Imaging
Anisotropy

@article {pmid42766267,
year = {2026},
author = {Kania, J and Zawar, I and Reyes, A and Williams, V and Sarkis, R and Punia, V and Williams, M and Ferguson, L and Arrotta, K and Busch, RM and Jones, J and Hermann, BP and McDonald, CR},
title = {Diagnostic accuracy of the ADAS-Cog-13 as a cognitive screening tool in older adults with focal epilepsy: A multicenter cross-sectional study.},
journal = {Epileptic disorders : international epilepsy journal with videotape},
volume = {},
number = {},
pages = {},
doi = {10.1002/epd2.70415},
pmid = {42766267},
issn = {1950-6945},
support = {R01NS120976/NH/NIH HHS/United States ; },
abstract = {OBJECTIVE: Cognitive impairment is common among older adults with epilepsy, and although the Montreal Cognitive Assessment (MoCA) has demonstrated validity as a screening tool in this population, additional efficient screening options are needed. Here we examine, for the first time, the diagnostic accuracy of the Alzheimer's Disease Assessment Scale-Cognitive-13 Item Subscale (ADAS-Cog-13) as a screening tool to identify cognitive impairment in older adults with focal epilepsy.

METHODS: Participants included 83 adults (ages ≥55) with focal epilepsy from the Brain, Aging, and Cognition in Epilepsy (BrACE) study and 83 age-, sex-, and education-matched cognitively healthy controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI-3). All completed the ADAS-Cog-13 and a comprehensive neuropsychological battery that was analyzed through the International Cognitive Disorders in Epilepsy (IC-CoDE) system to identify cognitive phenotypes (intact vs. impaired). Performance on the individual ADAS-Cog-13 total score and items was assessed, clinical and sociodemographic features characterized, and diagnostic efficiency statistics determined and compared with MoCA performance.

RESULTS: Focal epilepsy participants (mean age = 66.4 years) performed significantly worse across the ADAS-Cog-13 total score and 8 of the 13 individual test items compared with controls. The largest effect sizes were observed on verbal learning and memory tasks, particularly word recall (d = .87) and delayed word recall (d = 1.06). An ADAS-Cog-13 total score of ≥15 yielded optimal diagnostic efficiency (67.5% accuracy, 68.8% sensitivity, 66.7% specificity) for identifying cognitive impairment-similar to MoCA performance.

SIGNIFICANCE: The ADAS-Cog-13 is sensitive to detecting cognitive impairment in older adults with focal epilepsy and may represent a scalable screening option in this population. Additional comparative studies in older epilepsy populations are needed to determine the sensitivity of this measure to longitudinal change, cross-cultural applicability, and availability across languages.

PLAIN LANGUAGE SUMMARY: Cognitive decline is common among older adults with epilepsy. Although the Montreal Cognitive Assessment (MoCA) has been shown to be a valid screening tool in this population, additional options are needed. The ADAS-Cog-13 may be a useful screening option in epilepsy research and clinical care, although additional studies are needed to compare it with other cognitive screening tests and to confirm its applicability for clinical care and across healthcare settings and cultures.},
}

@article {pmid42766299,
year = {2026},
author = {Ruppert, E and Vermeiren, MR and Scop Medeiros, M and Povala, G and Soares, C and Rocha, A and de Oliveira Franco, A and Scarpatto Rodrigues, M and Oliveira, M and Mroué, R and Ferreira, PCL and Bauer-Negrini, G and Lussier, FZ and Amaral, L and Bellaver, B and Tissot, C and Masdeu, J and Tudorascu, DL and Karikari, T and Soleimani-Meigooni, DN and Fortea, J and Lowe, VJ and Oh, H and Pascual, B and Gordon, BA and Rosa-Neto, P and Baker, S and Ossenkoppele, R and van de Giessen, E and Pascoal, TA and , },
title = {A Harmonized Visual Reading Framework for Tau PET Staging in Alzheimer Disease.},
journal = {JAMA neurology},
volume = {},
number = {},
pages = {},
pmid = {42766299},
issn = {2168-6157},
abstract = {IMPORTANCE: Tau positron emission tomography (PET) can detect and stage Alzheimer disease pathology; however, current binary regulatory-approved visual interpretation focuses on advanced disease, limiting early detection and patient stratification.

OBJECTIVE: To develop and validate a harmonized tau PET visual reading framework across radiotracers that stages tau burden into 5 classes: negative, low, moderate, high, and atypical.

This prospective multicenter cross-sectional study among a cohort with head-to-head tau PET acquisitions was conducted from March 2022 to August 2025 and data analyzed from February to June 2026, with blinded visual reads performed by clinicians. The study was conducted at 9 sites across North America and Europe. Of those individuals enrolled in the HEAD (Head-to-Head Harmonization of Tau Tracers in Alzheimer's Disease) study, a proportion of participants aged 50 to 90 years who completed multitracer tau PET (2-4 scans) and cognitive assessments were included, spanning cognitively unimpaired to dementia.

EXPOSURES: Tau PET with 18F-MK-6240 (TAUKLARIFY, n = 681), 18F-flortaucipir (Tauvid, n = 644), 18F-RO948 (n = 150), and 18F-PI-2620 (n = 149); all participants underwent amyloid-β (Aβ) PET and magnetic resonance imaging.

MAIN OUTCOMES AND MEASURES: The primary outcomes were interrater and intertracer agreement for 5-class tau classification; prevalence ratio (PR) vs the regulatory-approved 18F-flortaucipir framework; and associations with cognition, Aβ burden, and plasma phosphorylated tau 217 (p-tau217).

RESULTS: Of 822 individuals enrolled in the HEAD study, 681 participants spanning cognitively unimpaired to dementia were included. Mean (SD) age was 69.3 (8.4) years, and 367 participants (53.9%) were female. The harmonized 5-class framework achieved excellent interrater agreement (κ = 0.77-0.85) and good to excellent intertracer agreement, highest between 18F-MK-6240 and 18F-flortaucipir (κ = 0.88). Compared with the regulatory-approved framework, the harmonized classification identified more tau-positive cognitively unimpaired participants (regulatory-approved binary: 26 of 364 participants; harmonized 18F-flortaucipir: 49 of 364 [PR = 1.89; 95% CI, 1.31-2.70; P = .001]; harmonized 18F-MK-6240: 71 of 364 [PR = 2.73; 95% CI, 1.95-3.83; P < .001]) and those with mild cognitive impairment (regulatory-approved binary: 100 of 223; harmonized 18F-flortaucipir: 123 of 223 [PR = 1.23; 95% CI, 1.12-1.35; P < .001]; harmonized 18F-MK-6240: 142 of 223 [PR = 1.42; 95% CI, 1.27-1.59; P < .001]), with convergence in dementia. Tau burden classes showed stepwise worsening of cognition, Aβ PET burden, and plasma p-tau217, with 1.4-fold, 3.2-fold, and 2.5-fold differences between the low and high tau classes, respectively.

CONCLUSIONS AND RELEVANCE: In this prospective multitracer cross-sectional study, a 5-class harmonized tau PET visual reading framework showed high interrater and intertracer agreement and detected more early-stage tau pathology than the regulatory-approved binary approach, with tau burden classes tracking stepwise with cognition and biomarkers. These findings support a standardized, tracer-agnostic framework for diagnostic categorization, therapeutic window identification, and clinical trial stratification.},
}

@article {pmid42766599,
year = {2026},
author = {Agbavor, F and Liang, H},
title = {Multimodal Dementia Prediction With Large Language Models: Cross-Attention Over Text, Audio, and Image.},
journal = {JMIR aging},
volume = {9},
number = {},
pages = {e93279},
pmid = {42766599},
issn = {2561-7605},
mesh = {Humans ; *Attention ; *Alzheimer Disease/diagnosis ; Large Language Models ; Female ; *Dementia/diagnosis ; Aged, 80 and over ; },
abstract = {BACKGROUND: Alzheimer disease (AD) is a leading cause of dementia, and there is growing interest in scalable approaches for early screening using speech-based tasks. While prior work has demonstrated promising results using either transcript-based language features or acoustic cues, most approaches remain unimodal or rely on simple fusion strategies that do not explicitly consider interactions across modalities.

OBJECTIVE: In this study, we propose an attention-based trimodal fusion framework that integrates text, audio, and image representations of the Cookie Theft picture, which serves as the shared visual stimulus in the picture-description task.

METHODS: Our method uses a new bidirectional cross-attention mechanism to achieve a unified multimodal embedding for downstream tasks. We evaluate the approach on 2 tasks: AD detection by classifying whether the participant has AD or not, and AD severity assessment by predicting Mini-Mental Status Examination cognitive scores.

RESULTS: On the AD detection task, trimodal fusion achieves the best overall performance (F1-score=0.8667, area under the receiver operating characteristic curve=0.9032), outperforming unimodal baselines, bimodal fusion, and conventional early or late fusion methods. For AD severity assessment, the proposed multimodal representation reduces prediction error of root mean squared error to about 4.20, improving over both unimodal and bimodal fusion settings. We further perform the ablation analysis to show that bidirectional cross-attention consistently outperforms conventional unidirectional cross-attention.

CONCLUSIONS: These results demonstrate that attention-based multimodal fusion can enhance dementia prediction from picture-description responses and provide a strong foundation for developing multimodal cognitive screening pipelines.},
}

Humans
*Attention
*Alzheimer Disease/diagnosis
Large Language Models
Female
*Dementia/diagnosis
Aged, 80 and over

@article {pmid42766920,
year = {2026},
author = {Liu, P and Harrison, TM and Snyder, HM and DeCarli, C and Maillard, P and Vemuri, P and Harvey, D and Koeppe, R and Jagust, W and Baker, LD and Landau, SM and , },
title = {Are the factors associated with cognitive performance generalizable across cohorts?.},
journal = {NeuroImage. Clinical},
volume = {52},
number = {},
pages = {104064},
doi = {10.1016/j.nicl.2026.104064},
pmid = {42766920},
issn = {2213-1582},
abstract = {OBJECTIVE: To examine whether vascular risk and brain atrophy account for cohort differences in the associations between tau burden and cognition across cognitive domains in U.S. POINTER and ADNI.

METHODS: We analyzed baseline data from 775 U.S. POINTER and 405 ADNI participants without significant cognitive impairment and matched on age, sex, clinical status, and APOE ε4 status. Cognitive outcomes included global cognition, verbal memory, and executive function. Regional tau (entorhinal and meta-temporal), vascular risk biomarkers, and structural MRI measures (entorhinal cortical thickness and hippocampal volume) were examined using linear regression models stratified by amyloid status and adjusted for age, sex, education, and average number of prior cognitive test exposures. Interaction terms (biomarker × cohort) were used to assess cohort differences. False discovery rate (FDR) correction was applied.

RESULTS: Greater tau burden was associated with poorer cognitive performance across global cognition, verbal memory, and executive function in ADNI compared to U.S. POINTER, particularly among Aβ + individuals (corrected p < .05). Unexpectedly, vascular risk biomarkers contributed minimally to cognitive variability in either cohort. Finally, brain atrophy, particularly hippocampal volume, made a tau-independent contribution to verbal memory in ADNI but not in U.S. POINTER, especially among Aβ + individuals (corrected p < .05).

CONCLUSIONS: Tau pathology in the presence of Aβ was a stronger predictor of cognition in ADNI than in U.S. POINTER, and this discrepancy was not explained by increased vascular risk or brain atrophy in U.S. POINTER. The drivers of cognition differed between cohorts in a way that is not easily attributable to clinical characteristics.},
}

@article {pmid42766994,
year = {2026},
author = {Xie, Z and Hong, YR and Armstrong, MJ and Wang, X and Jacobs, M},
title = {Dementia and End-of-Life Shared Decision-Making Among Older US Adults.},
journal = {Journal of the American Medical Directors Association},
volume = {27},
number = {11},
pages = {106490},
doi = {10.1016/j.jamda.2026.106490},
pmid = {42766994},
issn = {1538-9375},
abstract = {OBJECTIVES: To examine whether dementia is associated with differences in advance directive completion, decision-making needs near death, surrogate involvement, and concordance between expressed preferences for care and care received among older US adults.

DESIGN: Retrospective, nationally representative observational study using Health and Retirement Study Exit Interview data from 2010 to 2022.

SETTING AND PARTICIPANTS: The study included 5,389 decedents aged 50 years or older with complete information on dementia status, end-of-life decision-making outcomes, and selected covariates, representing approximately 22.2 million US decedents. Of these, 1,010 (weighted 17.7%) had dementia prior to death.

METHODS: Dementia status was identified from proxy reports of Alzheimer's disease or another form of dementia before death. Primary outcomes were advance directive completion and the occurrence of important medical decisions during the final days of life. Secondary outcomes included the decedent's ability to participate in decision-making, the primary decision-maker, and concordance between preferences for comfort-focused care and care received. Analyses incorporated Health and Retirement Study sampling weights, strata, and primary sampling units. Survey-weighted descriptive analyses and modified Poisson regression with robust variance estimation were used to compare decedents with and without dementia and estimate adjusted risk ratios (aRRs) and 95% CIs.

RESULTS: Decedents with dementia were more likely than those without dementia to have completed an advance directive (81.3% vs 69.1%; P < .001; aRR, 1.11; 95% CI, 1.07-1.15) and to have important medical decisions requiring resolution during the final days of life (54.3% vs 47.2%; P < .001; aRR, 1.09; 95% CI, 1.01-1.19). They were also substantially more likely to be unable to participate in end-of-life medical decision-making (78.9% vs 48.0%; P < .001), with children or grandchildren more frequently serving as the primary decision-makers (63.9% vs 45.6%; P < .001). Among decedents with documented advance directives, preferences for and receipt of comfort-focused care were high in both groups, with no significant differences by dementia status.

CONCLUSIONS AND IMPLICATIONS: Decedents with dementia experienced a distinct end-of-life shared decision-making pattern characterized not only by greater advance care planning but also greater decisional needs and reliance on surrogate decision-makers. These findings suggest that advance directives should be viewed as one component of an ongoing shared decision-making process rather than a substitute for it. Health care systems should complement advance care planning with early and ongoing caregiver engagement, structured decision support, and integration of palliative care across the dementia trajectory to help patients and families navigate evolving end-of-life decisions.},
}

@article {pmid42767135,
year = {2026},
author = {Alemdağ, B and Siyah, B and Alemdağ, İN and Berber, T and Güdük, ÖF},
title = {Elucidating the molecular nexus between dental developmental anomalies and chronic inflammatory diseases: A computational systems biology analysis of genomic sequence homology using matrix factorization.},
journal = {Computational biology and chemistry},
volume = {126},
number = {Pt 1},
pages = {109395},
doi = {10.1016/j.compbiolchem.2026.109395},
pmid = {42767135},
issn = {1476-928X},
abstract = {This entirely in silico, exploratory study investigates potential sequence-level links between periodontal disease, developmental dental anomalies such as molar-incisor hypomineralization (MIH), and selected systemic conditions including leukemias, amyotrophic lateral sclerosis, and Alzheimer's disease. To identify annotation-independent signatures, we applied Non-negative Matrix Tri-Factorization (NMTF) to k-mer/tf-idf representations of disease-associated gene and protein sequences compiled from OMIM, GeneCards, and PubMed for eleven curated disease groups; similarity values denote the proportion of the total between-cluster interaction (S-matrix) captured by a cluster. To guard against trivial explanations, we applied a composition-preserving sequence-shuffling test of the similarity magnitude and a degree-preserving (curveball) permutation test of the disease co-clustering that accounts for the dependence introduced by isoform records and shared genes, repeating the latter across a 1890-configuration parameter grid. At the gene level the dominant cluster was governed by the largest disease group (MIH) rather than by disease identity, whereas at the protein level periodontitis, dental anomalies, and leukemia subtypes co-clustered. The magnitude of the shares did not exceed a composition-preserving null (gene p=0.66; protein p=0.082), and under the degree-preserving null co-clustering was not significant at the gene level (p=0.36) but was significant, modest, and grid-robust at the protein level (p=0.033); canonical k-mer and coding-sequence controls confirmed that the gene-level weakness is intrinsic to nucleotide k-mers. These results delineate the protein level as the informative scale for annotation-independent cross-disease screening and identify the dental-leukemia axis as the candidate relationship for targeted follow-up. The findings are hypothesis-generating: the disease-associated gene sets were compiled with a non-systematic, literature-guided procedure, magnitudes do not exceed composition baselines, neither experimental or clinical validation nor quantitative benchmarking against alternative computational frameworks was performed, and any translational implication requires future validation.},
}

@article {pmid42767712,
year = {2026},
author = {Brandalise, F and Lorenzi, E and Melis, M},
title = {Vulnerability in the womb: Charting the effects of prenatal cannabinoid exposure to mitigate developmental actions on dopamine metabolic capacities and circuits.},
journal = {International review of neurobiology},
volume = {190},
number = {},
pages = {1-15},
doi = {10.1016/bs.irn.2026.08.020},
pmid = {42767712},
issn = {2162-5514},
mesh = {*Prenatal Exposure Delayed Effects/metabolism/chemically induced ; Humans ; Pregnancy ; Animals ; *Cannabinoids/adverse effects ; *Dopamine/metabolism ; Female ; *Brain/metabolism/drug effects ; *Dopaminergic Neurons/metabolism/drug effects ; Mesolimbic System ; },
abstract = {Prenatal cannabis exposure (PCE) is increasingly recognized as a major public health concern as cannabis use during pregnancy continues to rise worldwide. While early studies focused on cannabinoid receptor-mediated alterations in neurotransmission, emerging evidence indicates that PCE induces long-lasting developmental reprogramming affecting neural circuits, metabolism, and endocrine regulation. In this roadmap, we propose a shift from viewing PCE as a discrete synaptic disturbance to considering it a disorder of developmental coordination. We discuss how prenatal cannabinoid exposure may alter mesolimbic dopamine circuit maturation through the interaction of neuronal excitability, mitochondrial bioenergetics, and stress-related hormonal signaling. Particular attention is given to mitochondrial-circuit coupling in dopaminergic neurons and the potential role of mitochondrial cannabinoid receptors (mtCB1) in shaping long-term neuronal function. We further highlight the contribution of astrocytes, microglia, and neuroimmune processes in determining vulnerability or resilience trajectories. We propose that PCE generates latent neurobiological vulnerabilities that may emerge during adolescence or later life when challenged by environmental or physiological stressors. This framework provides new opportunities for early intervention, and prevention, while also offering insights into how early-life metabolic and mitochondrial dysfunction may contribute to lifelong brain vulnerability, including increased susceptibility to age-related neurodegenerative disorders such as Alzheimer's disease.},
}

*Prenatal Exposure Delayed Effects/metabolism/chemically induced
Humans
Pregnancy
Animals
*Cannabinoids/adverse effects
*Dopamine/metabolism
Female
*Brain/metabolism/drug effects
*Dopaminergic Neurons/metabolism/drug effects
Mesolimbic System

@article {pmid42767717,
year = {2026},
author = {Maiese, K},
title = {Running out the clock: Circadian rhythm dysfunction in cognitive disease.},
journal = {International review of neurobiology},
volume = {190},
number = {},
pages = {231-306},
doi = {10.1016/bs.irn.2026.08.015},
pmid = {42767717},
issn = {2162-5514},
mesh = {Humans ; Animals ; *Chronobiology Disorders/metabolism/physiopathology ; *Circadian Rhythm/physiology ; *Cognitive Dysfunction/metabolism/physiopathology ; *Cognition Disorders/physiopathology/metabolism ; },
abstract = {Lifespan is increasing such that within a few decades approximately twenty percent of the world's population is expected to be greater than sixty years of age. In concert with global aging of the population, neurodegenerative disorders have become the leading cause of disability with dementia now the seventh leading cause of death worldwide. Despite multi-faceted treatment approaches for disorders of cognition that include Alzheimer's disease and multiple sclerosis, present therapies ultimately cannot halt disease progression and eventually cognitive impairment continues unabated. Furthermore, co-morbidities, such as metabolic disorders with diabetes mellitus, also lack strategies to prevent disease progression. Given these clinical challenges for cognitive loss, innovative avenues of investigation that involve mammalian chronobiology with circadian rhythm clock genes and related pathways of aging, cellular senescence, oxidative stress, metabolic dysfunction, sleep fragmentation, apolipoprotein E, programmed cell death, silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae), nicotinamide adenine dinucleotide, the gut microbiota, and glucagon-like peptide-1 receptor agonism may offer exceptional promise for forging new strategies for cognitive disease treatment. These pathways are intimately linked to circadian rhythm processes, are complex in generating biological outcomes, can broadly influence clinical translation of both short- and long-term considerations for cognitive disease care, and necessitate dissection of their precise regulatory mechanisms with the benefit from early diagnostic platforms as well as artificial intelligence and machine learning applications to foster translation of these pathways into effective clinical treatments.},
}

Humans
Animals
*Chronobiology Disorders/metabolism/physiopathology
*Circadian Rhythm/physiology
*Cognitive Dysfunction/metabolism/physiopathology
*Cognition Disorders/physiopathology/metabolism

@article {pmid42767917,
year = {2026},
author = {Zhang, W and Smith, N and Veliz, EA and Zhao, B and Kandel, N and Joji, A and Chen, J and Ferreira, BCLB and Perez, M and Claure, X and Zhou, Y and Mintz, KJ and Zhang, F and Wang, C and Leblanc, RM},
title = {Nanoconjugation of chalcone derivatives and carbon nitride dots for the inhibition of tau aggregation.},
journal = {Colloids and surfaces. B, Biointerfaces},
volume = {},
number = {},
pages = {116175},
doi = {10.1016/j.colsurfb.2026.116175},
pmid = {42767917},
issn = {1873-4367},
abstract = {Tau aggregation is a pathological hallmark of Alzheimer's disease, yet small-molecule inhibitors targeting this process often face limitations in solubility, selectivity, and bioavailability. In this study, we engineered a library of hybrid nanostructures by covalently conjugating eleven structurally diverse chalcone derivatives to carbon nitride dots (CNDs), aiming to enhance their physicochemical stability and therapeutic efficacy. The resulting CND-chalcone conjugates exhibited favorable aqueous dispersibility and minimal cytotoxicity in HEK293 and HeLa cells. In vitro aggregation assays revealed that the conjugates modulated tau fibrillization in a structure-dependent manner, with several hybrids, particularly those containing hydroxyl or selectively positioned methoxy groups, showing strong inhibitory effects. Thioflavin-T fluorescence assays confirmed that the most active conjugates disrupted both nucleation and elongation phases of fibril formation. Notably, one hybrid (CNDs-S6) outperformed its free chalcone counterpart, suggesting synergistic interactions between the nanoparticle platform and ligand. These findings highlight the potential of CND-chalcone architectures as multifunctional nanoinhibitors and offer a rational approach to designing aggregation-targeting nanotherapeutics for neurodegenerative disease intervention.},
}

@article {pmid42767982,
year = {2026},
author = {López-González, FJ and Nemy, M and Jerele, C and Jiménez-Pérez, A and López-Martínez, MJ and Jonkman, L and Rábano, A and Sánchez-Juan, P and Grothe, MJ and Ferreira, D},
title = {Post mortem MRI of cholinergic white matter pathways across neurodegenerative diseases.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {9},
pages = {e71851},
pmid = {42767982},
issn = {1552-5279},
support = {//Next Generation funding UE/Mecanismo de Recuperación y Resiliencia/ ; PMP22/00022//ISCIII/ ; PI23/01314//ISCIII/ ; PI20/01011//ISCIII/ ; TED2021-131676B-100//ISCIII/ ; 101155955//European Union's Horizon Europe research and innovation programme/ ; 25-18359 M//Czech Science Foundation/ ; 2022-00916//Swedish Research Council/ ; 2025-02984//Swedish Research Council/ ; 20200505//Center for Innovative Medicine/ ; FoUI-988826//Center for Innovative Medicine/ ; FoUI-962240//regional agreement on medical training and clinical research of Stockholm Region/ ; FoUI-987534//regional agreement on medical training and clinical research of Stockholm Region/ ; FoUI-1023640//regional agreement on medical training and clinical research of Stockholm Region/ ; FO2021-0131//Swedish Brain Foundation/ ; FO2022-0175//Swedish Brain Foundation/ ; FO2023-0261//Swedish Brain Foundation/ ; FO2025-0214//Swedish Brain Foundation/ ; AF-968032//Swedish Alzheimer Foundation/ ; AF-980580//Swedish Alzheimer Foundation/ ; AF-994058//Swedish Alzheimer Foundation/ ; AF-1010553//Swedish Alzheimer Foundation/ ; AF-1031740//Swedish Alzheimer Foundation/ ; RYC2023-043746-I//Ramón and Cajal" fellowship/ ; CNS2024-154295//Spanish Ministry of Science, Innovation and Universities/ ; //European Social Fund (ESF)/ ; PI24/00089//Institute of Health Carlos III - European Regional Development Fund/ ; //Reina Sofia Foundation/ ; },
mesh = {Humans ; *White Matter/pathology/diagnostic imaging ; Female ; Male ; *Magnetic Resonance Imaging/methods ; Aged ; *Alzheimer Disease/pathology/diagnostic imaging ; *Neurodegenerative Diseases/pathology/diagnostic imaging ; Aged, 80 and over ; *Lewy Body Disease/pathology/diagnostic imaging ; Diffusion Tensor Imaging ; *Brain/pathology/diagnostic imaging ; Autopsy ; Neural Pathways/pathology/diagnostic imaging ; Middle Aged ; },
abstract = {INTRODUCTION: Cholinergic white matter pathway (CWMP) degeneration is central in Alzheimer's disease (AD) and Lewy body disease (LBD). CWMP degeneration can be assessed in vivo using magnetic resonance imaging (MRI) proxies, but neuropathological validation is limited.

METHODS: We studied post mortem in situ 3T MRIs of 55 brain donors with standardized neuropathologic assessment (AD, LBD, AD+LBD, other dementias, controls). CWMP integrity was assessed quantitatively using diffusion tensor imaging and visually using the Cholinergic Pathways Hyperintensities Scale (CHIPS) on fluid-attenuated inversion recovery MRI.

RESULTS: CWMP diffusivity was strongly associated with CHIPS (p < 0.001), independent of global white matter damage. AD and AD+LBD showed greater CWMP degeneration than LBD, other dementias, and controls (p < 0.05). Multivariate analyses across neuropathological variables identified hippocampal sclerosis and vascular co-pathology as strongest predictors for CWMP degeneration.

DISCUSSION: CWMP degeneration is pronounced in AD and mixed AD+LBD pathology and is additionally affected by vascular co-pathology and hippocampal sclerosis. CHIPS may serve as a clinically accessible MRI-based proxy of CWMP integrity.},
}

Humans
*White Matter/pathology/diagnostic imaging
Female
Male
*Magnetic Resonance Imaging/methods
Aged
*Alzheimer Disease/pathology/diagnostic imaging
*Neurodegenerative Diseases/pathology/diagnostic imaging
Aged, 80 and over
*Lewy Body Disease/pathology/diagnostic imaging
Diffusion Tensor Imaging
*Brain/pathology/diagnostic imaging
Autopsy
Neural Pathways/pathology/diagnostic imaging
Middle Aged

@article {pmid42768129,
year = {2026},
author = {Xu, Y and Wang, Q and Tang, H and Ji, G and Yang, R and Wu, D and Gui, Y},
title = {A multi-omics insight into the sex-specific burden of tobacco-associated neurodegeneration: trends, projections, and mechanistic clues from the TH gene.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {10},
pages = {},
pmid = {42768129},
issn = {1590-3478},
support = {22ZR1449800//Shanghai Science and Technology Program/Natural Science Foundation of Shanghai/ ; 81401038//National Natural Science Foundation of China/ ; 2020KY602//Zhejiang Province Medicine Health General Research Program/ ; },
mesh = {Humans ; Male ; Female ; *Parkinson Disease/genetics/epidemiology/etiology ; *Alzheimer Disease/genetics/epidemiology ; Global Burden of Disease/trends ; Sex Factors ; *Sex Characteristics ; Nicotine/metabolism ; *Neurodegenerative Diseases/genetics/epidemiology ; },
abstract = {BACKGROUND: Tobacco exposure significantly influences neurological health, yet its specific associations with Parkinson's disease (PD) and Alzheimer's disease and other dementias (ADOD), including mechanisms, require clarification.

METHODS AND MATERIALS: Using data from the Global Burden of Disease (GBD) 2021 study, multidimensional stratified comparisons of global PD and ADOD attributable to tobacco exposure were performed across dimensions including sex, socio-demographic index (SDI) quintiles, GBD sub-regions, and national levels. Furthermore, autoregressive integrated moving average and exponential smoothing models were incorporated to project trends until 2050. Bioinformatics analysis was conducted to identify key genes linking nicotine metabolism and sex differences.

RESULTS: Tobacco exposure exerted a negative modulatory effect on PD burden but increased ADOD risk. Marked sex-specific differences existed, with males more affected. Regional heterogeneity was pronounced: PD impact was strongest in East Asia, while ADOD burden was highest in high-SDI regions. Projections showed rising ASRs for males but a decline for females. Mechanistically, the TH gene was a key nexus connecting PD, nicotine pathways, and sex differences, potentially explaining the stronger effect in males.

CONCLUSIONS: Tobacco exposure differentially influences PD and ADOD, with distinct patterns by sex and region. It is detrimental for ADOD but may negatively modulate PD. The burden is projected to increase over the next three decades with persistent sex disparities. The TH gene may provides a mechanistic clue for the sex-heterogeneous effect against PD.},
}

Humans
Male
Female
*Parkinson Disease/genetics/epidemiology/etiology
*Alzheimer Disease/genetics/epidemiology
Global Burden of Disease/trends
Sex Factors
*Sex Characteristics
Nicotine/metabolism
*Neurodegenerative Diseases/genetics/epidemiology

@article {pmid42768165,
year = {2026},
author = {Simkhada, B and Liang, TY and Cui, X and Adeyosoye, M and Simkhada, B and Cabrerizo, M and Cid, RC and Burke, SL and Barreto, A and Rishe, N and Loewenstein, DA and Adjouadi, M},
title = {Multimodal prediction of MCI-to-dementia conversion over a two-year window.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {42768165},
issn = {2509-2723},
support = {CNS-1920182//National Science Foundation/ ; CNS-2018611//National Science Foundation/ ; NIA/NIH 1P30AG066506-01/NH/NIH HHS/United States ; NIA/NIH 5R01AG061106-02/NH/NIH HHS/United States ; 5R01AG047649-05/NH/NIH HHS/United States ; R01AG077677-04/NH/NIH HHS/United States ; },
abstract = {Mild cognitive impairment (MCI) represents a heterogeneous clinical state where some individuals remain stable while others progress to dementia. Identification of patients who are at high risk for near-term conversion remains a critical challenge for timely intervention. We developed an explainable multimodal machine-learning framework to predict progression from MCI to dementia within a clinically meaningful two-year period. We analyzed 2008 samples from 828 unique MCI subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI), including cognitive/functional assessments, demographic/genetic variables, and structural MRI features. Subjects were classified as stable MCI (sMCI, n = 1306) or progressive MCI (pMCI, n = 702) based on two-year outcomes. Machine learning algorithms were evaluated on unimodal and multimodal using nested cross-validation, and explainability was assessed using SHapley Additive exPlanations (SHAP) and permutation feature importance. The combination of cognitive assessments, demographics/risk factors and structural MRI features outperformed individual modalities, highlighting the complementary relationship between cognitive-functional decline and neuroanatomical degeneration. The best-performing model, a calibrated XGBoost, achieved a balanced accuracy of 81.28% ± 2.56% during cross-validation and 81.99% (bootstrap mean 81.97%, 95% CI: [78.22%-85.51%]) on an independent held-out test set. Explainable AI analyses identified functional impairment measures (Functional Activities Questionnaire, Clinical Dementia Rating - Sum of Boxes), cognitive performance scores (Alzheimer's Disease Assessment Scale - Cognitive Subscale 11-item version, Alzheimer's Disease Assessment Scale - Cognitive Subscale 13-item version, Mental State Examination), APOE ε4 status, and structural abnormalities within the hippocampus, lateral ventricle, parietal and temporal regions, and amygdala, as the most influential predictors of conversion. Short-term progression from MCI to dementia can be predicted with high accuracy using multimodal information obtained from a single clinical visit. The convergence of cognitive impairment and region-specific neurodegeneration emerged as the strongest indicator of conversion risk.},
}

@article {pmid42768200,
year = {2026},
author = {Wang, J and Meng, C and Xie, Y and Wang, S and Hu, Z and Jie, H and Mu, J and Duan, F and Huang, L},
title = {Tinosinenside A ameliorates Alzheimer's disease-related pathology in APP/PS1 mice, accompanied by reduced neuroinflammation and altered microglial phenotype-associated marker expression.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {42768200},
issn = {1432-1912},
abstract = {Tinospora sinensis (Lour.) Merr. has traditionally been used for its anti-inflammatory properties. Tinosinenside A (Tis A), a major sesquiterpene glycoside isolated from this plant, has shown neuroprotective activity; however, its effects on Alzheimer's disease (AD)-related neuroinflammation remain unclear. This study evaluated the effects of Tis A on behavioral impairment, neuroinflammation, and amyloid-β (Aβ) pathology in APPswe/PSEN1dE9 (APP/PS1) mice. APP/PS1 mice received oral Tis A for 6 months and were evaluated at 11 months of age using behavioral, histopathological, biochemical, and molecular analyses. Tis A partially improved behavioral performance, reduced Aβ plaque burden and pro-inflammatory cytokine levels, attenuated microglial overactivation, shifted microglial phenotype-associated marker expression toward a less pro-inflammatory profile, and alleviated neuronal apoptosis and histopathological damage. These effects were accompanied by reduced TLR4 and NLRP3 inflammasome-related protein expression and decreased phosphorylation of NF-κB p65 and IκBα. Collectively, these findings indicate that Tis A attenuates neuroinflammation and AD-related neuropathology while providing partial behavioral benefits in APP/PS1 mice, supporting its further investigation as a natural-product-derived therapeutic lead for AD.},
}

@article {pmid42768280,
year = {2026},
author = {Arcangeli, A and De Santi, LA and Santarelli, MF and Celi, S and Positano, V},
title = {Reject Option for Medical Image Classification Using CNN-Derived Latent-Space Neighbourhood Analysis.},
journal = {Journal of imaging informatics in medicine},
volume = {},
number = {},
pages = {},
doi = {10.1007/s10278-026-02318-y},
pmid = {42768280},
issn = {2948-2933},
abstract = {Reliable uncertainty estimation is a key requirement for the clinical adoption of convolutional neural networks (CNNs) in biomedical imaging. We propose a reject option framework that assesses prediction reliability by leveraging the local structure of the latent space. The method is based on three latent-space features: Simple Data Point Target Density (DPTD S), defined as the proportion of a sample's nearest neighbours sharing its label, a distance-weighted extension (DPTD W), and the k ∗ value. These metrics characterise local label agreement and intra-class consistency without relying on explicit parametric assumptions. A logistic regression rejector is trained post hoc using features derived from the latent representations of the base CNN. Experiments were conducted on two public neuroimaging datasets: ADNI (FDG-PET for Alzheimer's disease) and PPMI (DaTSCAN SPECT for Parkinson's disease). Using all three latent-space features, the rejector achieved AUC-ROC values of 0.843 (95% CI: 0.809-0.874) on ADNI and 0.884 (95% CI: 0.867-0.900) on PPMI, with corresponding eAURC values of 0.0278 (95% CI: 0.0193-0.0370) and 0.0169 (95% CI: 0.0133-0.0209), respectively. For the full-feature configuration, no significant difference from maximum softmax probability (MSP) was detected on ADNI for either AUC-ROC or eAURC, whereas MSP performed significantly better on PPMI for both metrics. The proposed framework provides a representation-based mechanism to assess prediction reliability through local latent-space structure. As a post-hoc approach, it can be integrated into existing CNN pipelines without modifying the underlying model, offering a practical tool for uncertainty-aware decision support in biomedical imaging.},
}

@article {pmid42768715,
year = {2026},
author = {Kinnunen, M and Vitikka, E and Krüger, J and Hoffmann, D and Haapasalo, A and Lleó, A and Belbin, O and Suhonen, NM and Borroni, B and Portaankorva, AM and Säisänen, L and Katisko, K and Solje, E},
title = {Non-motor symptoms questionnaire-based profiles in early-stage dementias: A prospective cohort study.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261487345},
doi = {10.1177/13872877261487345},
pmid = {42768715},
issn = {1875-8908},
abstract = {BackgroundCurrent knowledge regarding the nature and prevalence of non-motor symptoms across different types of dementia is limited. While Alzheimer's disease (AD), behavioral variant frontotemporal dementia (bvFTD), and dementia with Lewy bodies (DLB) are primarily characterized by cognitive and motor symptoms, several other features such as non-motor symptoms are also known to occur in all these conditions.ObjectiveTo assess non-motor symptoms in early-stage dementia and characterize symptom profiles across different neurodegenerative dementia diseases.MethodsA total of 64 AD, 38 bvFTD, and 17 DLB early-stage patients, along 63 cognitively healthy controls (HC), were prospectively recruited from Kuopio and Oulu University Hospitals. Non-motor symptoms were evaluated using the Non-Motor Symptoms Questionnaire (NMSQ), focusing on gastrointestinal, neuropsychiatric, cognitive, sleep-related and sensory-motor domains within three timeframes prior to the baseline visit.ResultsDLB patients exhibited the highest prevalence of non-motor symptoms across all domains. bvFTD and AD patients did not show disease group specific symptoms, but apathy and paranoidal thoughts appeared earlier in bvFTD than AD or DLB. Diplopia was reported by 14% of DLB patients (Fisher exact test, p = 0.035) one year before diagnosis. Neuropsychiatric and cognitive symptoms were more frequent in all dementia groups compared to HC (Fisher exact test, p < 0.01).ConclusionsNon-motor symptom profiles differ among these dementia subtypes even at early stages, suggesting their potential utility as early disease-specific indicators.},
}

@article {pmid42768750,
year = {2026},
author = {Jati, S and Kal, S and Munoz-Mayorga, D and Tang, K and Sahoo, D and Chen, X and Mahata, SK},
title = {Catestatin peptide ameliorates tauopathy and amyloidogenesis via adrenergic inhibition.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymthe.2026.09.022},
pmid = {42768750},
issn = {1525-0024},
abstract = {Neurodegenerative disorders such as Alzheimer's disease (AD), Corticobasal Degeneration (CBD), and Progressive Supranuclear Palsy (PSP) are characterized by tau aggregation, neuroinflammation, and progressive cognitive decline. Although metabolic dysregulation and neuropeptide imbalance have been linked to these disorders, the functional consequences of this imbalance and its reversal remain poorly understood. Our previous work identified chromogranin A (CgA), the gene encoding a pro-hormone for several metabolic peptides, as a key regulator of tau pathology. Here, we investigate Catestatin (CST), a CgA-derived peptide, for its role in modulating tauopathy. We report marked reductions in CST levels and an increase in Pancreastatin (PST) in the hippocampus and cortex of AD brains, as well as in the frontal cortex of CBD and the basal ganglia of PSP. CST-supplementation in cortical neuronal cultures and organotypic slice cultures (OTSC) reduced Tau phosphorylation and aggregation. In vivo, CST administration to PS19 tauopathy mice decreased pathological Tau species, attenuated gliosis, improved cognitive function, and reduced amyloid burden and neuroinflammation in 5xFAD mice. Mechanistically, CST reduced epinephrine levels in PS19 and 5xFAD mice, suppressed Protein Kinase A hyperactivation in PS19 and OTSC, and revealed a link between CST deficiency, adrenergic stress signaling, tauopathy-mediated neurodegeneration, and the therapeutic potential of CST supplement.},
}

@article {pmid42768846,
year = {2026},
author = {Gantenberg, JR and La Joie, R and Heston, MB and Ackley, SF and , },
title = {Do amyloid trajectories reach a ceiling? Evidence from iterative approximation and simulation.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {9},
pages = {e71781},
pmid = {42768846},
issn = {1552-5279},
support = {//NIH/NIA/ ; },
mesh = {Humans ; Positron-Emission Tomography ; *Alzheimer Disease/diagnostic imaging/metabolism/pathology ; Algorithms ; *Amyloid beta-Peptides/metabolism ; *Brain/diagnostic imaging/metabolism/pathology ; Computer Simulation ; *Amyloid/metabolism ; },
abstract = {INTRODUCTION: Qualitative models of Alzheimer's disease (AD) pathology often posit that amyloid accumulation follows a sigmoid curve, indicating that the rate of deposition wanes over time. Longitudinal positron emission tomography (PET) data now allow us to investigate amyloid accumulation trajectories with greater detail and over longer follow-up periods.

METHODS: We combine inferences from simulated amyloid trajectories, empirical PET data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), and the sampled iterative local approximation algorithm (SILA) to assess whether amyloid accumulation reaches a physiologic ceiling.

RESULTS: SILA reliably detects a ceiling in simulated scenarios that impose a sigmoid shape. Fit to ADNI, SILA does not appear to indicate the presence of a ceiling.

DISCUSSION: Amyloid trajectories may not reach a physiologic ceiling during the stages of AD typically observed while patients remain under follow-up in cohort studies. Illustrative models of biomarker cascades, while useful for conceptualizing pathologic processes, may not represent amyloid trajectory shapes accurately.},
}

Humans
Positron-Emission Tomography
*Alzheimer Disease/diagnostic imaging/metabolism/pathology
Algorithms
*Amyloid beta-Peptides/metabolism
*Brain/diagnostic imaging/metabolism/pathology
Computer Simulation
*Amyloid/metabolism

@article {pmid42768849,
year = {2026},
author = {Sun, H and Xin, X and Yan, J and Huang, T},
title = {Comparative Risk of Nonarteritic Anterior Ischemic Optic Neuropathy Among Glucagon-Like Peptide-1 Receptor Agonists: An Integrated Safety and Mechanistic Analysis.},
journal = {Diabetes, obesity & metabolism},
volume = {},
number = {},
pages = {},
doi = {10.1111/dom.71358},
pmid = {42768849},
issn = {1463-1326},
support = {//Young Clinical Scientist Training Program at Shanghai Medical College of Fudan University/ ; },
abstract = {AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for Type 2 diabetes (T2DM) and obesity, but emerging evidence links them to nonarteritic anterior ischemic optic neuropathy (NAION). Whether this risk differs across agents and the underlying mechanisms remains unclear. We aimed to compare the risks of NAION associated with different GLP-1RAs and to explore the potential molecular mechanisms underlying this adverse reaction.

MATERIALS AND METHODS: A network meta-analysis was performed to quantitatively compare the differences in NAION risk. Real-world pharmacovigilance data from the FDA Adverse Event Reporting System (FAERS) were used for validation. Network toxicology was further applied to identify central hub targets and signalling pathways. Molecular docking was conducted to evaluate the binding capacity of GLP-1RAs to central hub targets.

RESULTS: The network meta-analysis revealed significant differences in NAION risk across GLP-1RAs. Compared with non-GLP-1RA treatments, semaglutide showed the highest risk (HR = 1.538, 95% CI: 1.305-1.816), followed by liraglutide (HR = 1.251, 95% CI: 1.080-1.450). FAERS pharmacovigilance analysis suggested a strong disproportionate signal for semaglutide (ROR = 94.534, 95% CI: 83.093-107.552) and a statistically significant but weaker signal for liraglutide (ROR = 4.519, 95% CI: 2.617-7.802). Network toxicology identified CASP3 as the central hub target, and pathway enrichment analysis revealed that the underlying mechanisms were primarily related to Alzheimer's disease, neurodegeneration pathways, and lipid and atherosclerosis pathways. Molecular docking suggested that semaglutide and liraglutide had high binding affinity to CASP3.

CONCLUSIONS: The combined strategy of network meta-analysis, pharmacovigilance, network toxicology and molecular docking provides insights into possible risk differences and potential mechanisms, and may guide future research on the safety profile of GLP-1RAs.},
}

@article {pmid42768864,
year = {2026},
author = {Scodari, BT and Brown, R and Jiang, X and Shen, C and Ferber, K and Wu, S and Gao, F and Bullain, S and Millen, B},
title = {Enhancing early Alzheimer's disease clinical trials through prognostic score covariate adjustment.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {9},
pages = {e71849},
pmid = {42768864},
issn = {1552-5279},
support = {//Biogen/ ; },
mesh = {*Alzheimer Disease/diagnosis ; Humans ; Prognosis ; Disease Progression ; Female ; *Machine Learning ; Male ; Aged ; *Randomized Controlled Trials as Topic ; Mental Status and Dementia Tests ; *Clinical Trials as Topic ; },
abstract = {INTRODUCTION: A prognostic score (PS) summarizes a patient's expected disease progression and can increase the statistical efficiency of clinical trials when included as an analysis covariate.

METHODS: We pooled patient data from observational studies and randomized trials for early Alzheimer's disease (AD) and trained PS candidates to predict 18-month changes in the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) score. The efficiency gains achieved through covariate adjustment were evaluated in a held-out trial (N = 650).

RESULTS: A machine learning PS achieved a Pearson correlation of 0.48 between predicted and observed CDR-SB changes in an internal test set (N = 398). Adjusting for this PS in the held-out trial increased power from 80% to 87.9% (95% confidence interval [CI]: 85.5%-90.2%) with the original sample size. Alternatively, this approach could reduce the required sample size by 19.7% (95% CI: 13.7%-25.7%) while maintaining 80% power.

DISCUSSION: Our findings support the use of PS adjustment for enhancing the efficiency of early AD trials.},
}

*Alzheimer Disease/diagnosis
Humans
Prognosis
Disease Progression
Female
*Machine Learning
Male
Aged
*Randomized Controlled Trials as Topic
Mental Status and Dementia Tests
*Clinical Trials as Topic

@article {pmid42768866,
year = {2026},
author = {Wang, Y and Chen, Y and Kong, H and Chen, W and Su, F and Zheng, Y and Fang, Y and Lin, L and Zhou, J and Li, Y and Zhang, Y and Huang, A and Bergeron, MF and Jr, JOC and Ashford, JW and Zhou, X and Dai, Z and Sheng, W and Pei, Z},
title = {Unmasking preclinical Alzheimer's pathology: auditory distraction cost and occupational reserve jointly discriminate amyloid positivity in subjective cognitive decline.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {9},
pages = {e71874},
pmid = {42768866},
issn = {1552-5279},
support = {82271266//the National Natural Science Foundation of China/ ; c250130//Shenzhen Medical Research Fund/ ; 2022YFA1104904//the National Key Research and Development Program of China/ ; K0601902//Shanghai Medical Innovation and Development Foundation Project/ ; 2020B1212060017//Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases/ ; 2020B1111170002//Guangdong Provincial Clinical Research Center for Neurological Diseases/ ; 2015B050501003//Southern China International Joint Research Center for Early Intervention and Functional Rehabilitation of Neurological Diseases/ ; 2020A0505020004//Southern China International Joint Research Center for Early Intervention and Functional Rehabilitation of Neurological Diseases/ ; //Guangdong Provincial Engineering Center for Major Neurological Disease Treatment/ ; //Guangdong Provincial Translational Medicine Innovation Platform for Diagnosis and Treatment of Major Neurological Disease/ ; 201604020010//Guangzhou Clinical Research and Translational Center for Major Neurological Diseases/ ; },
mesh = {Humans ; Female ; Male ; *Cognitive Dysfunction/diagnosis/metabolism/pathology ; Aged ; *Alzheimer Disease/pathology/diagnosis/metabolism ; Positron-Emission Tomography ; *Amyloid beta-Peptides/metabolism ; *Cognitive Reserve/physiology ; Neuropsychological Tests ; },
abstract = {INTRODUCTION: Conventional cognitive instruments exhibit limited efficacy in detecting insidious cognitive decline in subjective cognitive decline (SCD) due to neural compensation. We hypothesized that auditory distraction during a visual memory task would unmask preclinical amyloid beta (Aβ) vulnerability.

METHODS: We evaluated 112 participants (SCD and mild cognitive impairment [MCI]) using the MemTrax test under quiet and noisy conditions to quantify distraction costs (d-MTxc). Aβ status and cognitive reserve were assessed via positron emission tomography and the Cognitive Reserve Index questionnaire (CRIq).

RESULTS: Aβ-positive SCD individuals performed normally in quiet but showed higher d-MTxc than Aβ-negative peers (11.17 ± 5.762 vs 6.67 ± 5.096). Higher CRIq-WorkingActivity (CRIW) scores identified Aβ positivity and moderated performance. The combination of d-MTxc and CRIW accurately classified Aβ positivity (AUC = 0.836), whereas MCI individuals exhibited metabolic network fragmentation.

DISCUSSION: Auditory distraction taxes cognitive capacity to expose compensatory failures coupled with Aβ burden. This paradigm, interacting with occupational reserve, offers a promising digital biomarker framework for preclinical Alzheimer's screening.},
}

Humans
Female
Male
*Cognitive Dysfunction/diagnosis/metabolism/pathology
Aged
*Alzheimer Disease/pathology/diagnosis/metabolism
Positron-Emission Tomography
*Amyloid beta-Peptides/metabolism
*Cognitive Reserve/physiology
Neuropsychological Tests

@article {pmid42768868,
year = {2026},
author = {Cervantes González, A and Morcillo-Nieto, AO and Serrano, S and Benejam, B and Videla, L and Barroeta, I and Fernández, S and Del Hoyo Soriano, L and Hernandez, AS and Maure-Blesa, L and Vaqué-Alcázar, L and Arranz, J and Rodríguez-Baz, Í and Aranha, MR and Perlaza, D and Lidón, L and Alcolea, D and Bejanin, A and Carmona-Iragui, M and Fortea, J and Lleó, A and Otto, M and Oeckl, P and Belbin, O},
title = {Changes in serum β-synuclein precede blood biomarkers of Alzheimer pathology in Down syndrome.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {9},
pages = {e71860},
pmid = {42768868},
issn = {1552-5279},
support = {23-PPG-674-2//ALS Association/ ; SFB1279//Deutsche Forschungsgemeinschaft/ ; FTLDc//Bundesministerium für Forschung und Technologie/ ; 01GI1007A//Bundesministerium für Forschung und Technologie/ ; R01AG061566/AG/NIA NIH HHS/United States ; FI22/00241//Instituto de Salud Carlos III/ ; 2021 SGR 00979//Departament de Salut, Generalitat de Catalunya/ ; AARG-22-923680/ALZ/Alzheimer's Association/United States ; 101156566//HORIZON EUROPE Health/ ; },
mesh = {Humans ; *Down Syndrome/blood/complications/pathology ; Female ; *Alzheimer Disease/blood/pathology/complications ; Biomarkers/blood ; Male ; *beta-Synuclein/blood ; Cross-Sectional Studies ; Middle Aged ; Adult ; tau Proteins/blood ; Neurofilament Proteins/blood ; Glial Fibrillary Acidic Protein/blood ; Aged ; Brain/pathology ; },
abstract = {INTRODUCTION: There is a need for early, objective markers of Alzheimer's disease (AD)-related synapse dysfunction in adults with Down syndrome (DS). The presynaptic protein β-synuclein is elevated in the blood of adults with DS. This study evaluates the positioning of these changes relative to changes in pathophysiological blood biomarkers along the AD continuum.

METHODS: We quantified serum β-synuclein using immunoprecipitation-mass spectrometry in a cross-sectional cohort (n = 131) spanning the AD continuum in adults with DS (n = 88) and cognitively unimpaired euploid controls (n = 43).

RESULTS: β-synuclein levels were elevated in individuals with DS (p < 0.001), preceding symptom onset by two decades and changes in other blood biomarkers (tau phosphorylated at threonine 217, neurofilament light, glial fibrillary acidic protein) by several years. Higher β-synuclein was associated with cortical atrophy (p < 0.001) and hypometabolism (p < 0.001) in AD-vulnerable regions and reduced episodic memory (p < 0.009).

DISCUSSION: These findings consolidate β-synuclein as an early blood-based biomarker of synaptic dysfunction and provide insight into early AD-related mechanisms.},
}

Humans
*Down Syndrome/blood/complications/pathology
Female
*Alzheimer Disease/blood/pathology/complications
Biomarkers/blood
Male
*beta-Synuclein/blood
Cross-Sectional Studies
Middle Aged
Adult
tau Proteins/blood
Neurofilament Proteins/blood
Glial Fibrillary Acidic Protein/blood
Aged
Brain/pathology

@article {pmid42768871,
year = {2026},
author = {Yetim, E and Ayhan, Y and Yildirim, MA and Volkan-Salanci, B and Ergün, EL and Çakmakli, GY},
title = {The Diagnostic Role of FDG-PET in Dementias Presenting with Language and Behavioral Symptom.},
journal = {Turk psikiyatri dergisi = Turkish journal of psychiatry},
volume = {37},
number = {},
pages = {77-82},
doi = {10.5080/u27876},
pmid = {42768871},
issn = {2651-3463},
mesh = {Humans ; *Positron-Emission Tomography ; Female ; Fluorodeoxyglucose F18 ; Male ; Biomarkers/cerebrospinal fluid ; Aged ; *Alzheimer Disease/diagnostic imaging/cerebrospinal fluid ; Middle Aged ; Neuropsychological Tests ; Radiopharmaceuticals ; Diagnosis, Differential ; Amyloid beta-Peptides/cerebrospinal fluid ; *Frontotemporal Lobar Degeneration/diagnostic imaging/cerebrospinal fluid ; },
abstract = {OBJECTIVE: This study aimed to assess the diagnostic contribution of Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) in neurodegenerative dementias presenting with language-predominant symptoms, with or without accompanying behavioral changes, and to evaluate the correspondence between PET-derived metabolic patterns and cerebrospinal fluid (CSF) biomarkers.

METHODS: Sixteen patients with language-predominant onset were categorized into two groups: Alzheimer’s disease (AD) spectrum (n=8) and the frontotemporal lobar degeneration (FTLD) spectrum (n=8). All participants underwent clinical evaluation, neuropsychological testing, and FDG-PET imaging. Cerebrospinal fluid biomarkers [Amyloid Beta (Aβ42), total tau, and phosphorylated tau] were analyzed in eligible individuals (n=6). The two groups were compared across demographic, clinical, and neuroimaging parameters.

RESULTS: FDG-PET revealed pronounced posterior temporoparietal hypometabolism in AD-spectrum patients, whereas FTLD-spectrum patients demonstrated frontal, insular, and anterior temporal metabolic involvement. Cerebrospinal fluid biomarker profiles consistently supported Alzheimer-type pathology among AD-spectrum cases. In the FTLD group, one patient exhibited borderline-low Aβ42; however, the corresponding FDG-PET pattern was characteristic of FTLD.

CONCLUSION: FDG-PET demonstrates a supportive role in differentiating AD from FTLD among patients presenting with language-predominant neurodegenerative syndromes. In scenarios where CSF biomarkers are unavailable or yield borderline values, FDG-PET-based metabolic signatures may offer additional guidance and can contribute to strengthening multimodal diagnostic frameworks in geropsychiatry settings.},
}

Humans
*Positron-Emission Tomography
Female
Fluorodeoxyglucose F18
Male
Biomarkers/cerebrospinal fluid
Aged
*Alzheimer Disease/diagnostic imaging/cerebrospinal fluid
Middle Aged
Neuropsychological Tests
Radiopharmaceuticals
Diagnosis, Differential
Amyloid beta-Peptides/cerebrospinal fluid
*Frontotemporal Lobar Degeneration/diagnostic imaging/cerebrospinal fluid

@article {pmid42768912,
year = {2026},
author = {Williams, CA and Rose, SE and Stamenkovic, V and Reid, AN and Travaglini, KJ and Smith, SEP and Young, JE},
title = {The Alzheimer's disease risk gene SORL1 is a regulator of excitatory neuronal function.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {9},
pages = {e71862},
pmid = {42768912},
issn = {1552-5279},
support = {P01AG079787//NIH/ ; T32AG52354/AG/NIA NIH HHS/United States ; MH113545//National Institute of Mental Health and Neurosciences/ ; //Cure Alzheimer's Fund/ ; 23AARG-1022491/ALZ/Alzheimer's Association/United States ; },
mesh = {*LDL-Receptor Related Proteins/genetics/metabolism ; Humans ; *Neurons/metabolism/physiology ; *Alzheimer Disease/genetics/metabolism ; *Membrane Transport Proteins/genetics/metabolism ; Animals ; Cells, Cultured ; Cerebral Cortex ; },
abstract = {INTRODUCTION: Synaptic dysfunction is an early feature of Alzheimer's disease (AD) and proper localization of proteins involved in pre- and post-synaptic composition is dependent on endosomal recycling and trafficking, cellular processes involving the AD risk gene sortilin-related receptor 1 (SORL1).

METHODS: We examined SORL1's role in synaptic protein composition and neuronal function in human excitatory cortical neurons. Synaptic protein interactions were analyzed using a mesoscale proteomics assay. Immunocytochemistry was used to visualize synaptic proteins and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunits. Neuronal function was measured with multi-electrode arrays.

RESULTS: Loss of SORL1 expression significantly changes many synaptic protein-protein interactions and patterns of expression. SORL1-deficient neurons exhibit hyperactivity that is primarily amyloid beta independent. SORL1-deficient neurons also have impaired network plasticity.

DISCUSSION: These findings further support a growing body of literature implicating early endosomal recycling defects as drivers of AD pathogenesis.},
}

*LDL-Receptor Related Proteins/genetics/metabolism
Humans
*Neurons/metabolism/physiology
*Alzheimer Disease/genetics/metabolism
*Membrane Transport Proteins/genetics/metabolism
Animals
Cells, Cultured
Cerebral Cortex

@article {pmid42769145,
year = {2026},
author = {Li, J and Liu, G and Wang, X and Song, Z and Chen, H and Hou, H and Hu, Q},
title = {Adult-onset hippocampal α7 nicotinic acetylcholine receptor loss rapidly drives Alzheimer-like neuropathology in mice.},
journal = {Frontiers in pharmacology},
volume = {17},
number = {},
pages = {1929468},
pmid = {42769145},
issn = {1663-9812},
abstract = {INTRODUCTION: The reduction of α7 nicotinic acetylcholine receptor (nAChR) in the hippocampus con-stitutes one of the neuropathological features observed in the brains of individuals with Alzheimer's disease (AD), and α7 nAChR is crucial to cognitive process. However, studies involving α7 nAChR knockout mice have not demonstrated any abnormal brain structure or damage to hippocampal neurons, a discrepancy likely driven by widespread developmental compensatory signaling reprogramming triggered by permanent whole-body α7 nAChR deletion from embryonic stages. This limitation renders traditional knockout lines unable to recapitulate the adult-onset, hippocampus-restricted α7 nAChR insufficiency characteristic of human AD, creating an unaddressed knowledge gap regarding whether isolated α7 nAChR loss in mature hippocampal neurons independently drives AD-related neurodegeneration and cognitive dysfunction.

METHODS: To resolve this limitation, we established a spatially and temporally restricted knockdown mouse model via stereotaxic intrahippocampal injection of adeno-associated virus encoding Chrna7-targeted short hairpin RNA (shRNA) in 4-month-old mice. We assessed behavioral performance via open field test, novel object recognition test, Y-maze and Barnes maze 1 month post-viral delivery to quantify cognitive function; 2 months after injection, we harvested brain tissues to measure Aβ deposition, tau hyperphosphorylation, neuronal loss, astrocytic and microglial activation using immunofluorescence staining, and performed transcriptome RNA sequencing to profile genome-wide transcriptional alterations.

RESULTS: The knockdown of α7 nAChR in the hippocampus of adult mice rapidly induced cognitive deficits, impairments in learning and memory, and led to the increase of amyloid-β levels, Tau protein aggregation, neuronal damage, and the activation of astrocytes and microglia. Transcriptomic analysis revealed that the differentially expressed genes were significantly enriched in pathways related to inflammatory signaling.

DISCUSSION: Our study demonstrates that selective depletion of hippocampal α7 nAChR in adult mice is sufficient to trigger a spectrum of AD-like pathological alterations. Importantly, our AAV-mediated region-specific knockdown paradigm fully eliminates the developmental compensatory bias inherent to constitutive global α7 nAChR knockout animals by restricting receptor suppression exclusively to mature hippocampal neurons in post-developmental mice, closely recapitulating the spatial-temporal pattern of α7 nAChR loss in human AD brains. Our work provides novel pharmacological insights into α7 nAChR as a promising therapeutic target for AD pathological intervention.},
}

@article {pmid42769165,
year = {2026},
author = {Yang, L and Yu, H and Hong, ZY and Liu, Z and Li, XJ and Ye, F},
title = {Resting-state EEG biomarkers of general and domain-specific cognitive impairment and plasma P-tau217 in patients with Alzheimer's disease and mild cognitive impairment.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1875216},
pmid = {42769165},
issn = {1664-2295},
mesh = {Humans ; *Alzheimer Disease/blood/physiopathology/diagnosis ; *Cognitive Dysfunction/physiopathology/blood/diagnosis ; Female ; *Electroencephalography ; Biomarkers/blood ; *tau Proteins/blood ; Male ; Aged ; Middle Aged ; Early Diagnosis ; },
abstract = {BACKGROUND: Early detection of Alzheimer's disease (AD)-related cognitive impairment remains challenging due to the lack of convenient, non-invasive screening tools.

OBJECTIVE: To explore the multidimensional utility of quantitative electroencephalography (EEG) as a complementary tool for early detection of AD-related cognitive impairment.

METHODS: Clinical data, electroencephalogram (EEG) records, cognitive scale scores and blood samples were collected. According to the established clinical diagnostic criteria, the participants were divided into three groups: cognitive normal group, mild cognitive impairment group (MCI) and Alzheimer's disease (AD) dementia group. Traditional statistical methods and machine learning algorithms were used to analyze the correlation between 200 EEG indexes and the severity of cognitive impairment, domain-specific cognitive impairment and plasma P-tau217 concentration.

RESULTS: A total of 360 participants (154 dementia patients with Alzheimer's disease, 116 mild cognitive impairment patients and 90 healthy controls) were included. The area under the curve (AUC) of EEG in 360 participants is 0.70-0.87, which can effectively distinguish cognitive dysfunction related to Alzheimer's disease. Among them, 102 participants improved the cognitive domain assessment scale, and the results showed that several EEG indexes were correlated with cognitive domain function score. The blood samples of 105 normal and MCI participants were tested for blood P-tau217 concentration. The relative power of right temporal lobe and right parietal lobe was negatively correlated with blood P-tau217 concentration, and the relative power of right parietal lobe was an independent influencing factor for the increase of blood P-tau217 level (AUC = 0.68).

CONCLUSION: Quantitative EEG indicators show potential as a complementary screening approach for AD-related cognitive impairment. Further validation in prospective, multicenter cohorts is needed before implementation in clinical practice.},
}

Humans
*Alzheimer Disease/blood/physiopathology/diagnosis
*Cognitive Dysfunction/physiopathology/blood/diagnosis
Female
*Electroencephalography
Biomarkers/blood
*tau Proteins/blood
Male
Aged
Middle Aged
Early Diagnosis

@article {pmid42769265,
year = {2026},
author = {Shen, L and Tong, W and Zhao, Y and Wu, B and Zhang, P and Kan, J},
title = {Explainable machine learning for Alzheimer's disease characterization using small-sample EEG data.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1900857},
pmid = {42769265},
issn = {1663-4365},
abstract = {Alzheimer's disease (AD) is associated with progressive cognitive decline and altered brain functional activity, yet objective and interpretable electrophysiological indicators remain insufficiently established. Resting-state electroencephalography (EEG) offers a low-cost and clinically accessible candidate, provided that the analysis is validated at the subject level and remains interpretable. This study evaluated an interpretable resting-state EEG framework for distinguishing AD patients from healthy control (HC) subjects. A total of 63 participants (36 AD and 27 HC) from a publicly available dataset were included. Subject-level spectral and nonlinear complexity features were extracted from 19 preprocessed scalp channels; missing-value imputation, feature screening, redundancy pruning, scaling, and model fitting were carried out within each fold of leave-one-subject-out cross-validation. Four linear classifiers were compared, and Ridge Logistic regression was retained for out-of-fold SHAP interpretation because of its balanced hard-label performance and direct compatibility with Linear SHAP. Ridge Logistic regression achieved an exploratory AUC of 0.912 (accuracy = 0.857, sensitivity = 0.778, specificity = 0.963) under a non-nested validation design. Across 30 independently balanced epoch resamples, mean AUC was 0.887 ± 0.020; using all accepted epochs yielded AUC = 0.917. SHAP analysis indicated that the classifier drew jointly on posterior α activity, frontal and temporal θ power, the θ/α ratio, and slow/fast ratio features. A classifier-independent microstate analysis revealed reduced putative Class B occurrence, increased putative Class C and Class D duration, and six FDR-corrected off-diagonal transition differences in AD; the three temporal effects persisted across repeated K = 4 initializations and matched K = 3-6 solutions. These findings suggest that resting-state EEG can provide non-invasive and interpretable information about AD-related functional alterations, pending validation in larger, independent cohorts.},
}

@article {pmid42769274,
year = {2026},
author = {Schechter, M and Sehtman-Shachar, DR and Fishkin, A and Mosenzon, O and Cukierman-Yaffe, T and Sharon, R and Leibowitz, G and Arkadir, D and Aharon-Hananel, G},
title = {Dementia progression with GLP-1 receptor agonists in people with mild cognitive impairment and type 2 diabetes: target-trial emulation study.},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {12},
number = {3},
pages = {e70315},
pmid = {42769274},
issn = {2352-8737},
abstract = {INTRODUCTION: In people with type 2 diabetes (T2D) without dementia, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improved cardiovascular, kidney, and mortality outcomes, with multiple real-world studies suggesting reduced risk of dementia onset. However, the EVOKE/EVOKE+ randomized-controlled trials (RCTs) found that oral semaglutide did not slow cognitive decline in individuals with early Alzheimer's disease (AD), most (86%) without T2D. It is unclear whether GLP-1 RA therapy influences progression to dementia in people with both T2D and mild cognitive impairment (MCI).

METHODS: In a target-trial emulation hypothesis-generating study using TriNetX global collaborative network data, we compared incident dementia (including AD) in adults with MCI and T2D without dementia, who were new users of GLP-1 RAs versus dipeptidyl peptidase-4 inhibitors (DPP4i).

RESULTS: We included 1320 propensity-score-matched (1:1) individuals who initiated GLP-1 RAs or DPP4i in the period 2010 to 2021 (702 women; mean age 67.2 years). Over up to 5 years of follow-up, incident dementia occurred in 101 and 132 participants initiating GLP-1 RAs and DPP4i, respectively (Cox proportional hazard ratio 0.74 [95% confidence interval [CI]: 0.57 to 0.95]). At a mean follow-up of 3.9 years, the respective Kaplan-Meier-derived cumulative incidences were 15.5% and 20.4% (absolute difference -4.9% [95% CI -9.4 to -0.4], number needed to treat of 21 [11 to 234] individuals to prevent one event). Various sensitivity analyses supported the primary analysis: comparing GLP-1 RAs with basal insulin, using alternative outcome definitions, repeating the analyses across baseline subgroups, and using a negative control outcome.

CONCLUSION: In this hypothesis-generating study, initiation of GLP-1 RAs versus DPP4i in people with T2D and MCI without dementia was associated with a lower risk of incident dementia.},
}

@article {pmid42769492,
year = {2026},
author = {Dong, K and Lang, J and Fu, J and Lan, J and Xu, F and Cheng, T and Jin, T and Wang, H and Wu, X and Luo, F},
title = {Total intravenous anesthesia facilitates early cognitive recovery compared with inhalational anesthesia in Alzheimer's disease patients after cervical lymphatic-venous anastomosis: a randomized controlled trial.},
journal = {American journal of translational research},
volume = {18},
number = {8},
pages = {7320-7330},
pmid = {42769492},
issn = {1943-8141},
abstract = {BACKGROUND: The optimal anesthesia method for Alzheimer's disease (AD) patients undergoing cervical lymphatic-venous anastomosis remains unclear. This study compared the effects of three general anesthesia techniques on postoperative cognitive outcomes in AD patients.

METHODS: In this prospective randomized controlled trial, 132 AD patients were assigned (1:1:1) to receive total intravenous anesthesia (TIVA), total inhalation anesthesia (IH), or combined intravenous-inhalation anesthesia (CI). The primary outcome was cognitive function assessed by MMSE, MoCA and CDR at postoperative day 7 (P7), P90 and P180. The secondary outcome was ADL scores at P180.

RESULTS: A total of 123 patients completed the study. At P7, MMSE scores in the TIVA group significantly improved from baseline (P < 0.05) and were superior to the IH and CI groups, which showed no significant change. At P90, MMSE scores improved in all three groups (P < 0.05), but returned to baseline by P180. No significant differences were observed in MoCA, CDR, or ADL scores at any time point.

CONCLUSION: Among the three anesthesia methods, TIVA was associated with better early cognitive performance at P7 as measured by MMSE, compared with inhalational anesthesia. However, this benefit was not sustained to P180 and no significant changes were observed in MoCA or CDR scores at any time point. These findings suggest that TIVA may reduce early postoperative psychomotor disturbance rather than confer sustained neurocognitive recovery in this population.},
}

@article {pmid42769555,
year = {2026},
author = {Huang, L and Cheng, P and Liu, G and Xiang, Y and Hong, Z and Le, W},
title = {Myelin Impairment and Regeneration in the Central Nervous System: Molecular Mechanisms, Diseases, and Prospective Therapeutic Targets.},
journal = {MedComm},
volume = {7},
number = {10},
pages = {e71017},
pmid = {42769555},
issn = {2688-2663},
abstract = {Myelin plasticity is fundamental to the formation of neural networks and the optimization of neural functions, shaping circuits governing emotion, cognition, sensation, and motor control. Synthesized by oligodendrocytes, myelin undergoes lifelong remodeling that demands high metabolic activity; this renders the myelin-oligodendrocyte unit highly susceptible to metabolic stress, aging, and pathological insults. While demyelination is the core hallmark of various chronic neurological disorders, this review specifically highlights its emerging role in Alzheimer's disease (AD). Myelin impairment is increasingly recognized as an early pathological event in AD, potentially preceding the classic accumulation of amyloid plaques and neurofibrillary tangles. Here, we provide a comprehensive overview of myelin structure and function, evaluating the potential of tracking myelin changes as early diagnostic biomarker for AD. We further synthesize recent evidence regarding myelin pathology across a spectrum of central nervous system disorders including multiple sclerosis, leukodystrophies, cerebral small vessel disease, psychiatric disorders, and traumatic injury, highlighting the underlying pathological mechanisms. Furthermore, we examine emerging therapeutic strategies, ranging from pharmacological interventions to noninvasive stimulation, aimed at restoring oligodendroglial function and promoting remyelination. Finally, we offer a forward-looking perspective on myelin regeneration research, emphasizing its critical potential as a novel therapeutic target for AD and other neurodegenerative conditions.},
}

@article {pmid42769580,
year = {2026},
author = {Li, M and Wang, Q and Li, J and Liu, Y and Chen, L and Liu, P and Guo, J},
title = {Spatial omics of neuroinflammation: insights across brain diseases.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1923995},
pmid = {42769580},
issn = {1664-3224},
mesh = {Humans ; Multiomics ; *Neuroinflammatory Diseases/metabolism/pathology/etiology ; Animals ; *Brain Diseases/metabolism/pathology ; Spatial Transcriptomics ; Proteomics/methods ; *Brain/metabolism/pathology ; Metabolomics/methods ; Microglia/metabolism ; },
abstract = {Neuroinflammation is a common pathological feature of diverse brain diseases, but inflammatory activity is rarely distributed uniformly across diseased tissue. Instead, microglia, astrocytes, infiltrating immune cells and inflammatory mediators are often organized around specific pathological structures, including amyloid plaques, demyelinated lesion rims, ischemic borders, necrotic tumor regions and perivascular white matter compartments. Although bulk and dissociation-based single-cell approaches have defined many inflammatory cell states, they cannot determine where these states reside, how they relate to local pathology, or whether inferred cell-cell interactions occur within plausible spatial neighborhoods. Spatial omics addresses this limitation by preserving molecular information within intact tissue architecture. In this review, we summarize major spatial transcriptomic, proteomic, metabolomic and same-section multi-omic technologies, with emphasis on the types of neuroinflammatory questions each platform can answer. We then examine how spatial omics has reshaped the understanding of neuroinflammation across Alzheimer's disease and tauopathies, multiple sclerosis, ischemic stroke, glioma, infection-related neuroinflammation and aging. Across these settings, spatial studies have revealed plaque-associated glial niches, lipid- and iron-enriched lesion rims, core-penumbra inflammatory zonation, and hypoxic or perivascular immune microenvironments. These findings suggest that neuroinflammation should be understood not only as a set of molecular or cellular states, but also as a spatially organized tissue process shaped by local pathology, cellular adjacency and microenvironmental gradients and spatial compartments. Finally, we discuss the limitations of current spatial maps, including resolution, human tissue constraints and insufficient functional validation, and outline future directions toward integrated, temporal and clinically translatable spatial atlases.},
}

Humans
Multiomics
*Neuroinflammatory Diseases/metabolism/pathology/etiology
Animals
*Brain Diseases/metabolism/pathology
Spatial Transcriptomics
Proteomics/methods
*Brain/metabolism/pathology
Metabolomics/methods
Microglia/metabolism

@article {pmid42769715,
year = {2026},
author = {Arriola-Pacheco, F and Pinzón-Té, AL and Serrano-Piña, R and Carrillo-Ávila, BA and Díaz-Zúñiga, J and Melgar-Rodríguez, S and Martínez-Aguilar, VM},
title = {Periodontitis and Alzheimer's disease, common pathways in down syndrome.},
journal = {Frontiers in dental medicine},
volume = {7},
number = {},
pages = {1930049},
pmid = {42769715},
issn = {2673-4915},
abstract = {Down Syndrome (DS) involves widespread systemic issues, including a near-universal development of early-onset Alzheimer's Disease, driven by factors beyond Amyloid Precursor Protein (APP) over-expression, such as chronic neuroinflammation and endosomal dysfunction. High prevalence of periodontitis in this population acts as a significant source of peripheral inflammation that may accelerate this cognitive decline, necessitating further study into the bidirectional, pro-inflammatory links between systemic health and neurodegeneration in DS. This review analyzes the common pathophysiological pathways linking periodontitis and AD development within the DS population, evaluating how oral dysbiosis acts as a systemic driver of neurodegeneration. We synthesized current molecular, microbiological, and clinical evidence evaluating the bidirectional relationships between trisomy 21-induced immune dysfunction, severe periodontitis, and accelerated cognitive decline. Individuals with DS exhibit a heightened susceptibility to aggressive, early-onset periodontitis starting as early as age six. This chronic oral dysbiosis facilitates microbial translocation, allowing periodontal pathogens (e.g., Porphyromonas gingivalis) and their virulence factors to cross the blood-brain barrier via circulatory or trigeminal routes. In the central nervous system, these pathogens encounter microglial populations already genetically primed by trisomy 21. This induces an exacerbated M1 microglial phenotype response, triggering sustained neuroinflammation, defensive over-deposition of Amyloid-β (Aβ) plaques, and upregulation of GSK-3β, which accelerates Tau protein hyperphosphorylation. While bidirectional links are strongly indicated, current literature lacks robust longitudinal studies connecting periodontal, microbiological, and cognitive data to establish definitive causality. Early clinical intervention and management of gum disease present a critical therapeutic window to delay the onset and slow the progression of AD in this vulnerable population.},
}

@article {pmid42769797,
year = {2026},
author = {Patel, MM and Nguyen, MD and Pistone, ES and Chowdhury, A and Phan, MH and El Ayadi, A and Song, J and Erickson, M},
title = {Out of the Fire, Into the Fog: Association Between Early Mechanical Ventilation and Delirium in Hospitalized Burn Patients.},
journal = {Cureus},
volume = {18},
number = {8},
pages = {e114981},
pmid = {42769797},
issn = {2168-8184},
abstract = {Introduction Delirium is a common and clinically significant complication among hospitalized burn patients, associated with increased morbidity, mortality, and healthcare utilization. While multiple factors contribute to delirium risk, mechanical ventilation has been associated with delirium, although this relationship may reflect underlying illness severity and ICU-level treatment exposure. However, large-scale, multicenter administrative analyses comparing coded outcomes between mechanically ventilated and non-ventilated burn patients remain limited. Methods A retrospective cohort study was conducted using the TriNetX (TriNetX, LLC, Cambridge, Massachusetts, United States) database to identify adult hospitalized burn patients with International Classification of Diseases (ICD)-coded burns involving ≥20% total body surface area. Patients were stratified into two cohorts based on receipt of mechanical ventilation within five days of the index burn event. Exclusion criteria included age <18 years and diagnoses of dementia, Alzheimer's disease, substance use disorders, or other conditions associated with baseline cognitive impairment. Cohorts were propensity score matched for age, sex, race, ethnicity, ICD-coded burn extent history, hypertension, diabetes, ischemic heart disease, sepsis, inhalation injury, and respiratory disorders. Outcomes assessed within 30 days included administratively documented delirium, disorientation, mortality, anxiety disorders, depressive disorders, and acute stress-related disorders. Results There were 1,541 patients in each cohort after matching. Ventilated patients had higher rates of administratively documented delirium (risk ratio (RR): 2.16, 95% CI: 1.51-3.09, p<0.0001), mortality (RR: 5.06, 95% CI: 4.23-6.05, p<0.0001), anxiety disorders (RR: 1.88, 95% CI: 1.58-2.21, p<0.0001), disorientation (RR: 3.39, 95% CI: 2.27-5.06, p<0.0001), and acute stress-related disorders (RR: 1.77, 95% CI: 1.40-2.22, p<0.0001). Depressive disorders were not significantly different between cohorts (RR: 1.42, 95% CI: 0.85-2.39, p=0.19). Discussion Early mechanical ventilation was associated with higher rates of administratively documented delirium, mortality, anxiety disorders, disorientation, and acute stress-related disorders among adult hospitalized burn patients. However, these findings likely reflect both ICU-level treatment exposure and substantial residual confounding by underlying illness severity. Early mechanical ventilation may identify a high-risk subgroup that warrants structured neurocognitive monitoring, psychological screening, sedation-conscious care, and post-extubation support. Given the observational design and reliance on administrative coding, these findings should be interpreted as hypothesis-generating.},
}

@article {pmid42769842,
year = {2026},
author = {Hou, C and Gao, Y and Wang, H},
title = {Exercise timing as a potential temporal regulator of neurolymphatic physiology in neurodegenerative proteinopathies: a mechanistic framework.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1879617},
pmid = {42769842},
issn = {1662-4548},
abstract = {Although physical activity is consistently associated with lower risks of cognitive decline, dementia, and Parkinson's disease, most exercise research in neurodegeneration still defines exposure by dose-based variables such as duration, intensity, frequency, step count, and cardiorespiratory fitness. This framework is useful for public-health guidance but biologically incomplete for progressive proteinopathies, in which the temporal accumulation and dissemination of misfolded proteins are central to disease evolution. In this review, we propose a temporal intervention framework in which exercise timing is treated as a mechanistic variable that may influence neurodegenerative biology through glymphatic-meningeal lymphatic clearance, vascular pulsatility, circadian alignment, and sleep architecture. We focus on Alzheimer's disease and Parkinson's disease because tau and α-synuclein propagation are disease-relevant processes that may be most amenable to intervention during preclinical or prodromal stages. Morning exercise may act primarily through circadian entrainment, afternoon exercise through vascular-metabolic stimulation, appropriately timed evening or low-intensity activity through sleep-related pathways, and sedentary fragmentation through effects on daytime cerebrovascular dynamics and rest-activity rhythm stability. Although the glymphatic-meningeal lymphatic axis provides a plausible link between timed exercise and extracellular protein handling, current human evidence remains indirect and relies heavily on imaging surrogate markers. Future matched-dose trials should integrate accelerometry, sleep physiology, circadian measures, vascular assessments, neurolymphatic imaging, and disease-specific protein biomarkers, including tau PET, plasma p-tau217, and α-synuclein seed amplification assays. Timed exercise should therefore be viewed as a testable biological perturbation that may clarify whether movement timing influences protein propagation in early neurodegenerative disease, not as a proven disease-modifying treatment.},
}

@article {pmid42770059,
year = {2026},
author = {Miller, DA and Price, HB and Wang, W and Wax, A},
title = {OCT-guided angle-resolved low-coherence interferometry for microstructural analysis of the human retina.},
journal = {Biomedical optics express},
volume = {17},
number = {9},
pages = {4870-4883},
pmid = {42770059},
issn = {2156-7085},
abstract = {Angle-resolved low-coherence interferometry (a/LCI) is an optical technique for extracting depth-resolved angular scattering profiles from biological tissues. Analysis of these angular scattering profiles can be used to compute the two-point spatial correlation function, which enables quantification of tissue structural heterogeneity at sub-cellular length scales. Building on previous work that combined a/LCI and optical coherence tomography (OCT) to detect biomarkers of Alzheimer's disease (AD) in ex vivo murine models, this study seeks to translate the platform for noninvasive scattering analysis of the human retina. The resulting system combines OCT image guidance, enabled by our high-performance, low-cost OCT platform, with parafoveal angular scattering measurements in each retinal quadrant, using 2D a/LCI. Measurements from 11 healthy participants were used to characterize retinal microstructure at length scales ranging from 4.8 μm to 9.5 μm. Our results revealed consistent variations in the structural correlations across retinal layers and quadrants, establishing baseline healthy measurements for future studies. This dual-modality approach offers a promising framework for improving diagnostic sensitivity in a variety of retinal and neurological disorders.},
}

@article {pmid42770090,
year = {2026},
author = {Zhuang, F and Wen, Z and Davatzikos, C and Shen, L},
title = {Expert-Driven Survival Machines: Improving Stratification and Interpretability in Multiple Clinical Cohorts.},
journal = {ACM-BCB ... ... : the ... ACM Conference on Bioinformatics, Computational Biology and Biomedicine. ACM Conference on Bioinformatics, Computational Biology and Biomedicine},
volume = {2026},
number = {},
pages = {29},
pmid = {42770090},
abstract = {Survival prediction plays a central role for healthcare providers and clinical researchers. Accurate risk stratification enables early intervention and improved patient management. Most existing deep survival models learn one common feature representation for all patients, which may hide important differences between patient subgroups. In contrast, a Mixture-of-Experts (MoE) framework allows different parts of the model to focus on different patient patterns, leading to more individualized representations. Therefore, in this work, we propose a mixture-of-experts enhanced adaptive deep clustering survival framework (AdaCSM) for modeling such heterogeneous survival patterns. We introduce a routing-based expert mechanism that enables conditional specialization within a parametric survival modeling framework. The proposed architecture allocates patients to specialized risk predictors dynamically while preserving the patient survival and subtype clustering objectives. We compare our method with state-of-the-art survival and deep clustering models on multiple real-world longitudinal clinical cohorts spanning diverse disease domains. The proposed method demonstrates improved predictive performance and leads to interpretable results in survival analysis.},
}