07/2026 journal articles
EDITORIAL: ELIGIBILITY OF MEN VS. WOMEN IN ALZHEIMER’S TRIALS: INCLUSIVE VS. REPRESENTATIVE
Joshua D. Grill, Daniel L. Gillen
J Prev Alz Dis 2026;7(13)
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CITATION:
Joshua D. Grill ; Daniel L. Gillen (2025): Editorial: Eligibility of men vs. women in Alzheimer’s trials: Inclusive vs. representative. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100625
TOP FIVE ALZHEIMER DISEASE TRIAL ELIGIBILITY CRITERIA FAVOR MEN COMPARED TO WOMEN IN A CLINIC-BASED COHORT
Lieza G. Exalto, Siti S. Syaziyah, Xiaotian T Fang, Niels D. Prins, Sietske A.M. Sikkes, Wiesje M. van der Flier, Everard G.B. Vijverberg, Yvonne M.F. Lim
J Prev Alz Dis 2026;7(13)
Show summaryHide summaryBACKGROUND: Less women participate in Alzheimer Disease (AD) trials compared to their estimated representation in the global dementia population.
OBJECTIVES: We aimed to apply five most commonly used eligibility criteria to a real-world memory clinic population to compare male and female eligibility according to these criteria.
DESIGN: Observational.
SETTING: Memory clinic setting.
PARTICIPANTS: Consecutive patients (2000–2024) from Amsterdam Dementia Cohort with a diagnosis of mild cognitive impairment (MCI) or AD (n = 3835).
MEASUREMENTS: Free-text eligibility criteria of n = 608 phase II and III AD drug trials were downloaded from ClinicalTrials.gov (March 28, 2025). A machine-learning model was trained and validated to extract all eligibility criteria. Next the criteria were applied on observational real world data from on memory clinic diagnostic work-up.
RESULTS: Top 5 most common AD clinical trial eligibility criteria were 1) no other central nervous system disorder related to cognitive impairment (84%), 2) participation of a caregiver (72%), 3) MMSE (66%, range 20–30), 4) no comorbidities, specifically vascular and mental health (62%), 5) no contra-indications for study procedures such as lumbar puncture, MRI and PET (59%). Applying the abovementioned criteria results in 33% of men and 23% of women remaining eligible (p<.001). Main reason for non-eligibility is caretaker absence (applicable for 20% of men and 38% of women) and low MMSE (32% of man and 54% of women).
CONCLISION: Based on five commonly used eligibility criteria of AD clinical trials, women in our clinic-based cohort are less eligible for participation in AD drug trials than men. This discrepancy was mainly attributed to lack of caregiver presence and lower MMSE at presentation. These results provide clues for trial design to facilitate more equal inclusion of women.
CITATION:
Lieza G. Exalto ; Siti S. Syaziyah ; Xiaotian T Fang ; Niels D. Prins ; Sietske A.M. Sikkes ; Wiesje M. van der Flier ; Everard G.B. Vijverberg ; Yvonne M.F. Lim (2025): Top five Alzheimer Disease trial eligibility criteria favor men compared to women in a clinic-based cohort. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100580
EDITORIAL: BEYOND TARGET ENGAGEMENT: RNA THERAPEUTICS AND THE NEUROIMMUNE CHALLENGE IN TAUOPATHIES
Elizabeth Anne Breen
J Prev Alz Dis 2026;7(13)
Show summaryHide summaryRecent advances in RNA-based therapeutics have generated considerable interest as a strategy for targeting tau pathology in Alzheimer's disease and related tauopathies. In their review, Rajbanshi and colleagues provide a comprehensive overview of emerging RNA therapeutic modalities, translational challenges, and ongoing clinical development efforts. This commentary discusses the promise of RNA-based approaches within the broader context of contemporary neurodegeneration research, highlighting the persistent disconnect between molecular target engagement and meaningful clinical benefit. Emerging evidence suggests that successful disease modification may require consideration of neuroimmune dysfunction, biological heterogeneity, and disease stage in addition to molecular pathology. The future success of RNA therapeutics will likely depend not only on achieving precise modulation of tau biology but also on translating these advances into sustained cognitive and functional benefit for patients.
CITATION:
Ece Bayram (2025): Editorial: Beyond target engagement: RNA therapeutics and the neuroimmune challenge in tauopathies. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100626
RNA-BASED THERAPEUTICS FOR ALZHEIMER’S DISEASE AND RELATED TAUOPATHIES: CHALLENGES AND OPPORTUNITIES
Binita Rajbanshi, Ilaria Brentari, Michela Alessandra Denti, Jeffrey L. Cummings, Anuj Guruacharya
J Prev Alz Dis 2026;7(13)
Show summaryHide summaryTauopathies are neurodegenerative diseases characterized by pathological tau protein accumulation. Though therapies involving monoclonal antibodies and small-molecule inhibitors have progressed, they have so far failed in multiple clinical trials, underscoring the need for innovative molecular approaches. RNA-based therapies offer an alternative disease-modifying approach by being able to target tau at its molecular origin. Diverse modalities, such as mRNA, ASO, RNAi, and SSO, offer distinct promises. Though their challenges are equally diverse, they also share common problems. This review examines the nascent field of RNA therapeutics for tauopathies, outlining emerging modalities, translational barriers, molecular targets, clinical trials, and patent trends.
CITATION:
Binita Rajbanshi ; Ilaria Brentari ; Michela Alessandra Denti ; Jeffrey L. Cummings ; Anuj Guruacharya (2025): RNA-based therapeutics for Alzheimer’s disease and related tauopathies: challenges and opportunities. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100585
EDITORIAL: TIME TO PAY ATTENTION TO SLEEP FOR ALZHEIMER’S DISEASE IN WOMEN
Ece Bayram
J Prev Alz Dis 2026;7(13)
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CITATION:
Ece Bayram (2025): Editorial: Time to pay attention to sleep for Alzheimer’s disease in women. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100624
SLEEP COMPLAINTS AND GENETIC RISK OF ALZHEIMER’S DISEASE IN OLDER WOMEN: ASSOCIATIONS WITH MEMORY AND TAU DEPOSITION
Kitty K Lui, Xin Wang, Melanie A Dratva, Ella T. Lifset, Jordan Stiver, Nadine C. Heyworth, Qian Shen, Michael Thomas, Pamela N. DeYoung, Atul Malhotra, Erin E. Sundermann, Sarah J. Banks
J Prev Alz Dis 2026;7(13)
Show summaryHide summaryBACKGROUND: Emerging evidence point to a bidirectional relationship between sleep disturbances and Alzheimer’s disease (AD). Poor sleep may be an overlooked risk factor for older women, who are disproportionately affected by AD and report worse subjective sleep quality than men. High genetic AD risk—characterized by the polygenic hazard score (PHS), including apolipoprotein (APOE) ε4 carriership—may further compound the effects of disrupted sleep on AD, particularly for older women.
OBJECTIVE: This study examined the moderating effect of genetic AD risk on subjective sleep as it related to memory and tau burden in a sample of older women.
PARTICIPANTS: The sample consisted of older women (≥65 years old) from the Women Inflammation Tau Study.
MEASUREMENT: Participants completed the Pittsburgh Sleep Quality Index (PSQI), Rey Auditory Learning Test, and Brief Visuospatial Memory Test-Revised. They also underwent [18]F-MK6240 positron emission tomography. Tau burden was calculated in composite regions across Braak stages. Genetic risk groups were characterized by PHS stratified at the 75th percentile. PSQI global score × PHS group interactions on memory composite scores (N = 69) and tau burden (N = 63) were examined.
RESULTS: PSQI global score × PHS group interactions were observed on visual memory and pathological tau in Braak regions III/IV (ps<0.10). Poorer subjective sleep was associated with worse visual memory and greater limbic tau deposition only among higher genetic risk women (ps<0.04). No significant associations were observed for verbal memory or tau in Braak regions I/II or V/VI.
CONCLUSION: Older women with elevated genetic AD risk and subjective sleep difficulties may be at greater risk for visual memory deficits and tau burden in regions affected in early AD. This suggests that sleep complaints may represent a promising AD risk factor. Improving sleep may be a potential intervention target for AD mitigation and prevention, particularly for older women.
CITATION:
Kitty K Lui ; Xin Wang ; Melanie A Dratva ; Ella T. Lifset ; Jordan Stiver ; Nadine C. Heyworth ; Qian Shen ; Michael Thomas ; Pamela N. DeYoung ; Atul Malhotra ; Erin E. Sundermann ; Sarah J. Banks (2025): Sleep complaints and genetic risk of Alzheimer’s disease in older women: associations with memory and tau deposition. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2025.8
TETANUS, DIPHTHERIA AND PERTUSSIS VACCINATION AND RISK FOR INCIDENT DEMENTIA AMONG ADULTS WITH DOWN SYNDROME
Kimberly Schiel, Joanne Salas, Anjani Urban, Daniel F. Hoft, Jeffrey F. Scherrer
J Prev Alz Dis 2026;7(13)
Show summaryHide summaryBACKGROUND: Adult vaccination is inversely associated with incident Alzheimer’s Disease and Related Dementias.
OBJECTIVES: We determined if Tetanus, Diphtheria and Pertussis (Tdap) vaccination was linked to incident Alzheimer’s Disease and dementia among adults with Down Syndrome, 50% of whom develop Alzheimer’s Disease by age 60.
DESIGN: This is a retrospective cohort study using TriNetX nationally distributed electronic health records from 2013 to 2024.
SETTING: Historical medical record data.
PARTICIPANTS: 5591 patients with Down Syndrome across the United States. Eligible patients were free of Alzheimer’s Disease and dementia prior to index. Index date could occur 1/1/2015 to 1/1/2020 allowing for 5 to 10 years of possible follow-up time.
MEASUREMENTS: Vaccination was measured using product name and procedure codes and Alzheimer’s Disease and dementias was defined by ICD-10 codes.
RESULTS: The mean age of the cohort was 50.0 (±8.3), 50.1% were female and 72.1% were White. After controlling for confounding, Tdap vaccination vs. remaining without Tdap vaccination was associated with lower Alzheimer’s Disease and dementia risk (HR=0.74; 95%CI:0.57–0.98).
CONCLUSIONS: In a cohort of patients with Down Syndrome, Tdap vaccination was associated with a 26% lower risk for Alzheimer’s Disease and dementia. This is a novel and important finding because existing studies of vaccination and reduced risk for Alzheimer’s Disease and dementia have been among cognitively intact adults. This study reveals benefits of vaccination even among those at high risk for Alzheimer’s Disease and dementia due to Down Syndrome. Future studies are needed to understand the mechanisms underlying this relationship.
CITATION:
Kimberly Schiel ; Joanne Salas ; Anjani Urban ; Daniel F. Hoft ; Jeffrey F. Scherrer (2025): Tetanus, diphtheria and pertussis vaccination and risk for incident dementia among adults with down syndrome. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100583
EPIGENETIC AGING AND BLOOD BASED NEURODEGENERATION MARKERS IN LASI-DAD
Jung Ki Kim, Thalida E. Arpawong, Bharat Thyagarajan, Jennifer A. Smith, Sithara Vivek, Scott Ratliff, Sharmistha Dey, Jinkook Lee, Eileen M. Crimmins
J Prev Alz Dis 2026;7(13)
Show summaryHide summaryDNA methylation (DNAm)-based epigenetic clocks are emerging biomarkers of biological aging and have been linked to cognitive decline and dementia, but their relationship with blood-based neurodegenerative biomarkers remains understudied in low- and middle-income countries (LMIC). Using the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (LASI-DAD), we examined whether epigenetic aging was associated with levels and changes in neurodegenerative biomarkers among adults aged ≥60 years. Seven epigenetic clocks were derived from DNAm data and related to plasma levels of glial fibrillary acidic protein (GFAP), neurofilament light (NfL), phosphorylated tau 181 (pTau181), total tau, Amyloid-β (Aβ)42, Aβ40 and Aβ42/Aβ40 measured at two time points. Baseline accelerated epigenetic aging was associated with higher levels of neurodegenerative biomarkers, including pTau181, GFAP, and NfL, with more consistent associations with increases in GFAP and NfL for morbidity- and mortality-trained clocks. These findings support the utility of epigenetic clocks as scalable tools for identifying risk of neurodegeneration in LMIC settings.
CITATION:
Jung Ki Kim ; Thalida E. Arpawong ; Bharat Thyagarajan ; Jennifer A. Smith ; Sithara Vivek ; Scott Ratliff ; Sharmistha Dey ; Jinkook Lee ; Eileen M. Crimmins (2025): Epigenetic aging and blood based neurodegeneration markers in LASI-DAD. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100595
HYPERTENSION ACTS TOGETHER WITH AΒ PATHOLOGY IN LATE-LIFE TO PROMOTE MEMORY LOSS
Lucas U Da Ros, João Pedro Ferrari-Souza, Marco Antônio de Bastiani, Lucas A. Hauschild, Bruna Bellaver, Pamela C.L. Ferreira, Douglas Teixeira Leffa, Guilherme Povala, Firoza Z. Lussier, Mira Chamoun, Gleb Bezgin, Andrea L. Benedet, Nesrine Rahmouni, Arthur C. Macedo, Kaj Blennow, Nicholas Ashton, Henrik Zetterberg, Wyllians Vendramini Borelli, Diogo O. Souza, Tharick A. Pascoal, Pedro Rosa-Neto, Eduardo R. Zimmer, Alzheimer’s Disease Neuroimaging Initiative
J Prev Alz Dis 2026;7(13)
Show summaryHide summaryMidlife hypertension (HTN) contributes to cognitive decline in Alzheimer's disease (AD). However, the exact effect of late-life HTN on the AD pathology and on cognitive decline is still controversial. Here, we aimed to assess the impact of HTN and AD pathology in cognitively unimpaired (CU) individuals over 65 years of age on longitudinal cognitive decline. We evaluated 637 CU individuals from two independent cohorts (475 CU individuals from the ADNI cohort; and 162 CU individuals from the TRIAD cohort), with a follow-up of up to 6 years. Linear mixed-effects models showed that HTN and Aβ acted together to promote longitudinal cognitive decline, especially memory loss, in a synergistic way, with a dose-dependent association of blood pressure and Aβ pathology. Hence, HTN in late-life confers additional risk for cognitive decline, particularly for memory loss, in CU individuals at risk of developing dementia due to AD and is a potential modifiable risk factor even at older age.
CITATION:
Lucas U Da Ros ; João Pedro Ferrari-Souza ; Marco Antônio de Bastiani ; Lucas A. Hauschild ; Bruna Bellaver ; Pamela C.L. Ferreira ; Douglas Teixeira Leffa ; Guilherme Povala ; Firoza Z. Lussier ; Mira Chamoun ; Gleb Bezgin ; Andrea L. Benedet ; Nesrine Rahmouni ; Arthur C. Macedo ; Kaj Blennow ; Nicholas Ashton ; Henrik Zetterberg ; Wyllians Vendramini Borelli ; Diogo O. Souza ; Tharick A. Pascoal ; Pedro Rosa-Neto ; Eduardo R. Zimmer ; for theAlzheimer’s Disease Neuroimaging Initiative (): Hypertension acts together with Aβ pathology in late-life to promote memory loss. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100579
INTERACTION OF DIET AND PHYSICAL ACTIVITY ON DEMENTIA RISK: THE ROTTERDAM STUDY
Muhammed Lamin Sambou, M. Arfan Ikram, M. Kamran Ikram, Jeremy A. Labrecque, Frank J. Wolters
J Prev Alz Dis 2026;7(13)
Show summaryHide summaryBACKGROUND: Diet and physical activity have been reported as independent risk factors for dementia, but few published studies have investigated the interactive effects of the two on dementia risk. Understanding their synergism could help shape more effective prevention strategies. Therefore, we assessed the potential interactions between MIND diet adherence and physical activity on the long-term risk of incident dementia in the population-based Rotterdam Study.
METHODS: Between 2009–2013, 5016 participants of the population-based Rotterdam Study were recruited (mean age 69.76 years, 57.9% women). All participants filled in questionnaires regarding their adherence to the MIND diet and time spent on moderate to vigorous physical activity (Metabolic Equivalent of Task [MET] hours per week). Participants were subsequently followed for incident dementia until January 1, 2021. We applied multivariable Cox regression models to assess interaction on both additive and multiplicative scales.
RESULTS: Median values were 7.5 for the MIND diet score and 28.0 for MET hours per week. Of all 5016 participants, 2718 (54.2%) adhered to a high MIND diet score (≥7.5), and 2513 (50.1%) reached at least 28.0 MET hours per week. During a mean follow-up of 6.6 years, 365 participants (7.8%) developed dementia. Both higher physical activity and higher MIND-diet score were independently associated with a lower risk of dementia, but there was no significant interaction on the additive scale (RERI [95%CI]=-0.42 [-1.26 to 0.12]), nor on the multiplicative scale (HRinteraction=0.71 [0.46–1.09]). Sex-stratified analysis suggested a negative interaction between exposures in women, but not in men.
CONCLUSION: Better adherence to the MIND-diet and higher levels of physical activity were each associated with a reduced risk of dementia, but overall there was no indication that their joint effects were greater than the product or sum of their individual parts. Potential sex differences warrant further exploration in different populations.
CITATION:
Muhammed Lamin Sambou ; M. Arfan Ikram ; M. Kamran Ikram ; Jeremy A. Labrecque ; Frank J. Wolters (2025): Interaction of diet and physical activity on dementia risk: the Rotterdam study. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100594
NEUROPSYCHIATRIC SYMPTOMS AND DEMENTIA DEVELOPMENT: A 15-YEAR POPULATION-BASED STUDY
Francesca Remelli, Giulia Grande, Serhiy Dekhtyar, Erika J Laukka, Caterina Trevisan, Stefano Volpato, Laura Fratiglioni, Federico Triolo
J Prev Alz Dis 2026;7(13)
Show summaryHide summaryBACKGROUND: Mild Behavioral Impairment (MBI) has been proposed to detect neuropsychiatric symptoms (NPS) associated with dementia development, but evidence from population-based settings is limited.
OBJECTIVES: To (i) investigate the association between NPS in late life and the onset of dementia over 15 years in community-dwelling older adults, and (ii) test the interplay of NPS and Cognitive Impairment, No Dementia (CIND) in dementia development.
METHODS: 2597 dementia-free individuals aged 60+ from a longitudinal population-based cohort underwent cognitive assessments over 15 years. Thirty clinically-assessed NPS were mapped into five domains and, within each domain, a z-score was computed from the sum of the NPS’s points. MBI was identified when the z-score was above 1.5 standard deviations (SDs) in at least one of 5 neuropsychiatric domains. Based on a cognitive battery, CIND was defined as scoring ≥1.5 SDs below age-specific means in at least one cognitive domain. Dementia was diagnosed by DSM-IV criteria following standardized procedures.
RESULTS: MBI, present in 16.1% of the sample, was associated with a higher hazard of incident dementia over 15 years (multi-adjusted hazard ratio [HR] 1.68, 95% confidence interval [CI] 1.31–2.17). Decreased motivation and social inappropriateness were the domains associated with incident dementia (HR 2.23, 95%CI 1.59–3.14 and HR 3.29, 95%CI 1.83–5.94, respectively). Compared to those with neither, individuals with either MBI (HR 1.37, 95%CI 1.00–1.90) or CIND (HR 2.22, 95%CI 1.73–2.84) had increased dementia incidence, especially when co-occurring (HR 4.41, 95%CI 3.04–6.39).
CONCLUSIONS: Late life NPS, especially with co-occurring cognitive impairment, was associated with a higher dementia incidence.
CITATION:
Francesca Remelli ; Giulia Grande ; Serhiy Dekhtyar ; Erika J Laukka ; Caterina Trevisan ; Stefano Volpato ; Laura Fratiglioni ; Federico Triolo (2025): Neuropsychiatric symptoms and dementia development: a 15-year population-based study. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100596
PLASMA BRAIN-DERIVED P-TAU217 OUTPERFORMS OTHER P-TAU SPECIES IN DETECTING ABNORMAL BRAIN AMYLOID IN AN ASIAN COHORT OF OLDER PEOPLE WITH CEREBROVASCULAR DISEASE BURDEN
Joyce R. Chong, Saima Hilal, Narayanaswamy Venketasubramanian, Michael Schöll, Nicholas J. Ashton, Henrik Zetterberg, Christopher P. Chen, Mitchell K.P. Lai
J Prev Alz Dis 2026;7(13)
Show summaryHide summaryBACKGROUND: Plasma brain derived-p-Tau217 (BD-p-Tau217) may outperform total-p-Tau217 in detecting brain amyloid burden and warrants evaluation.
OBJECTIVES: To perform head-to-head comparison of plasma BD- as well as total-p-Tau181, p-Tau217 and p-Tau231 for detecting beta-amyloid positivity (Aβ+), evaluate reference ranges for Aβ+, and assess the prognostic utility of BD-p-Tau217 reference ranges.
DESIGN: Observational study.
SETTING: Participants recruited from memory clinics and the community in Singapore.
PARTICIPANTS: 213 participants, including 44 cognitively normal, 107 cognitively impaired no dementia, and 62 dementia (mean [SD] age, 73 [1] years; 121 females).
MEASUREMENTS: Amyloid status (Aβ- [n = 139] vs Aβ+ [n = 74]) was determined by positron emission tomography (PET). Plasma BD-p-Tau and total-p-Tau were measured using the NULISAseq™ CNS Disease Panel 120. The diagnostic performance for detecting Aβ+, reference ranges (three-range: 95% specificity/95% sensitivity); binary: maximizing Youden index), and the prognostic performance of p-Tau biomarkers were evaluated.
RESULTS: Plasma BD-p-Tau217 (AUC = 0.965) outperformed other BD- and total-p-Tau species in detecting PET Aβ+ (AUC = 0.823–0.937; all p ≤ 0.008). Using a three-range reference, BD-p-Tau217 achieved positive predictive value (PPV) and negative predictive value (NPV) of 90% and 97%, respectively. Proportion of participants in the intermediate-risk group was 7% (n = 14). Applying a binary reference, BD-p-Tau217 achieved both a specificity and sensitivity of 92%, with PPV and NPV of 86% and 96%, respectively. BD-p-Tau217-derived high-risk group exhibited faster cognitive decline than the low-risk group.
CONCLUSIONS: Risk stratification for PET Aβ+ based on plasma BD-p-Tau217 suggests superior diagnostic and prognostic utility, warranting further validation.
CITATION:
Joyce R. Chong ; Saima Hilal ; Narayanaswamy Venketasubramanian ; Michael Schöll ; Nicholas J. Ashton ; Henrik Zetterberg ; Christopher P. Chen ; Mitchell K.P. Lai (2025): Plasma brain-derived p-Tau217 outperforms other p-Tau species in detecting abnormal brain amyloid in an Asian cohort of older people with cerebrovascular disease burden. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100615
CLASS-LEVEL AGGREGATION OBSCURES CLINICALLY RELEVANT HETEROGENEITY IN ANTI-AMYLOID ANTIBODY TRIALS: COMMENTS ON A COCHRANE REVIEW BY INDIVIDUAL MEMBERS OF THE EADC
Kristian Steen Frederiksen, Mercè Boada, Lutz Frölich, Milica Kramberger, Nikolaos Scarmeas, Everard Vijverberg, Pieter Jelle Visser, Gunhild Waldemar, Eric Westman, Henrik Zetterberg, Sebastiaan Engelborghs, Frank Jessen
J Prev Alz Dis 2026;7(13)
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CITATION:
Kristian Steen Frederiksen ; Mercè Boada ; Lutz Frölich ; Milica Kramberger ; Nikolaos Scarmeas ; Everard Vijverberg ; Pieter Jelle Visser ; Gunhild Waldemar ; Eric Westman ; Henrik Zetterberg ; Sebastiaan Engelborghs ; Frank Jessen (2025): Class-level aggregation obscures clinically relevant heterogeneity in anti-amyloid antibody trials: comments on a Cochrane review by individual members of the EADC. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100598
REDUCTIONS IN NEUROPSYCHIATRIC SYMPTOMS AFTER LECANEMAB TREATMENT AND THEIR ASSOCIATIONS WITH IMAGING MARKERS OF Β-AMYLOID CLEARANCE
Yaping Yan, Daoyan Hu, Linlin Kong, Kaicheng Li, Jun Su, Yingzhe Wu, Hongwei Zhan, Hong Zhang, Yidan Sun, Xiaofeng Dou, Peiyu Huang, Jiong Zhou
J Prev Alz Dis 2026;7(13)
Show summaryHide summaryBACKGROUND: Anti–amyloid-β (Aβ) therapies can slow cognitive decline and reduce cerebral amyloid burden in Alzheimer’s disease (AD). Neuropsychiatric symptoms (NPS) are highly prevalent across the disease course and substantially contribute to disability and caregiver burden. However, whether Aβ clearance translates into improvements in NPS remains unclear.
METHODS: We enrolled 144 individuals with AD-related mild cognitive impairment or AD dementia who received intravenous lecanemab infusions. Standardized clinical rating scales, including the Neuropsychiatric Inventory, and amyloid PET were assessed at baseline (V0), 6 months (V1), and 12 months (V2). Longitudinal changes in clinical function and amyloid burden were analyzed.
RESULTS: Lecanemab treatment was associated with robust reductions in amyloid PET biomarkers and significant short-term reductions in NPS scores in patients who completed follow-up. Longitudinal analyses showed that reductions in total NPI scores were significantly associated with amyloid-β clearance in the insular cortex. Reductions in the hyperactivity subsyndrome were associated with amyloid reduction across a broader network, including the frontal and temporal lobes, striatum, and insular cortex.
CONCLUSIONS: In this real-world cohort, lecanemab was associated with short-term reductions in NPS. Changes in NPS severity were linked to regional amyloid-β clearance.
CITATION:
Yaping Yan ; Daoyan Hu ; Linlin Kong ; Kaicheng Li ; Jun Su ; Yingzhe Wu ; Hongwei Zhan ; Hong Zhang ; Yidan Sun ; Xiaofeng Dou ; Peiyu Huang ; Jiong Zhou (2025): Reductions in neuropsychiatric symptoms after lecanemab treatment and their associations with imaging markers of β-amyloid clearance. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100600
ADAPTING THE SPANISH HEALTHCARE SYSTEM FOR DISEASE-MODIFYING TREATMENTS IN EARLY-STAGE ALZHEIMER’S DISEASE
R. Sánchez Valle, A. Lleó Bisa, A. Villarejo Galende, E. Cuartero Rodríguez, J. Escudero-Torrella, N. Bargallo Alabart
J Prev Alz Dis 2026;7(13)
Show summaryHide summaryBACKGROUND: The emergence of disease-modifying therapies targeting amyloid pathology represents a major paradigm shift in the management of Alzheimer disease (AD). However, their implementation poses substantial organizational, infrastructural, and clinical challenges for health systems.
OBJECTIVES: To identify the key challenges and establish priority recommendations for the effective incorporation of amyloid-targeting therapies into the Spanish National Health System.
DESIGN, SETTING, AND PARTICIPANTS: This multiphase consensus study was conducted within the Spanish National Health System between September 2024 and July 2025. The study comprised a narrative literature review, qualitative research, regional workshops, and a modified RAND/UCLA Delphi process. A total of 56 experts participated, including a scientific committee of 6 Alzheimer disease specialists and an expert panel of 50 multidisciplinary professionals involved in AD care.
MEASUREMENTS: Identification of key challenges across the AD care pathway; development, evaluation, and prioritization of consensus-based recommendations; and estimation of patient demand, including projected increases in day hospital activity and magnetic resonance imaging utilization.
RESULTS: Ten key challenge areas were identified, encompassing early detection and referral, diagnostic confirmation, assessment of patient eligibility, treatment administration in day hospitals, monitoring of amyloid-related imaging abnormalities, evaluation of treatment effectiveness, infrastructure and capacity, professional training, patient information and support, and health care planning. Of the 43 recommendations assessed, 38 were rated as appropriate and necessary, with 14 prioritized for immediate implementation. Demand estimation models indicated that 11 to 26 patients per 100,000 inhabitants could be treated under current care patterns, increasing to 17 to 115 per 100,000 inhabitants under alternative eligibility scenarios.
CONCLUSIONS: This consensus defines the clinical, organizational, and infrastructural requirements necessary to integrate amyloid-targeting therapies into routine care within the Spanish National Health System. The prioritized recommendations define immediate actions to address the challenges identified and may serve as a reference for other health systems facing similar implementation processes.
CITATION:
R. Sánchez Valle ; A. Lleó Bisa ; A. Villarejo Galende ; E. Cuartero Rodríguez ; J. Escudero-Torrella ; N. Bargallo Alabart (2025): Adapting the spanish healthcare system for disease-modifying treatments in early-stage alzheimer’s disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100586
DIAGNOSTIC PERFORMANCE OF AN AUTOMATED PLASMA P-TAU217 CHEMILUMINESCENT ASSAY FOR DETECTING AΒ PATHOLOGY IN A CHINESE MEMORY CLINIC COHORT
Shuai Chen, Feng-Yu Wang, Rong Li, Chang Fu, Jing-Yu Shao, Yu Shen, Kai Ma, Xiao-Di Hao, Lin Cao, Jun-Ling Xu, Jie-Wen Zhang
J Prev Alz Dis 2026;7(13)
Show summaryHide summaryBACKGROUND: Blood-based biomarkers have emerged as promising tools for detecting Alzheimer’s disease (AD) pathology, but validation of automated plasma assays in Chinese clinical populations remains limited. This study evaluated the diagnostic performance of a fully automated chemiluminescent plasma biomarker assay for detecting amyloid-β (Aβ) pathology in a Chinese memory clinic cohort under different pre-analytical conditions.
METHODS: We enrolled 409 cognitively impaired participants from a single-center memory clinic, using amyloid-β positron emission tomography (Aβ-PET) as the reference standard. Plasma samples were analyzed under two pre-analytical conditions: frozen batch-processed samples from a historical cohort (n = 198) and freshly collected samples analyzed in real time in a prospective cohort (n = 211). Additionally, 95 participants underwent tau-PET imaging. Six plasma biomarkers were quantified using the Vazyme® AD Assay.
RESULTS: Across cohorts, p-tau217, p-tau217/Aβ42 ratio, and NfL/p-tau217 ratio consistently achieved excellent diagnostic performance (AUCs 0.92–0.95), followed by p-tau181 (AUCs 0.86–0.90). GFAP (AUCs 0.82–0.83) and the Aβ42/40 ratio (AUCs 0.76–0.81) showed moderate discriminative performance. Plasma p-tau217 alone achieved diagnostic accuracy comparable to composite biomarker models. A dual cut-point strategy reduced the indeterminate zone to <30%, with positive predictive values of 0.97–0.99 and negative predictive values of 0.86–0.87. Plasma p-tau217 was also significantly associated with tau-PET burden in both meta-temporal and neocortical regions (P < 0.001).
CONCLUSION: This automated chemiluminescent plasma biomarker assay demonstrated high diagnostic accuracy for detecting Aβ pathology in a Chinese memory clinic cohort under different pre-analytical conditions. The findings support its potential utility as a practical blood-based biomarker approach in specialized clinical settings, while further multicenter studies are needed to confirm its generalizability across broader populations and healthcare environments.
CITATION:
Shuai Chen ; Feng-Yu Wang ; Rong Li ; Chang Fu ; Jing-Yu Shao ; Yu Shen ; Kai Ma ; Xiao-Di Hao ; Lin Cao ; Jun-Ling Xu ; Jie-Wen Zhang (2025): Diagnostic performance of an automated plasma p-tau217 chemiluminescent assay for detecting Aβ pathology in a Chinese memory clinic cohort. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100613
MULTIMODAL BIOMARKER CHARACTERIZATION OF AMNESTIC OBJECTIVE SUBTLE COGNITIVE DECLINE IN AGING AND PRECLINICAL ALZHEIMER’S DISEASE
David López-Martos, Raffaele Cacciaglia, Marc Suárez-Calvet, Gemma Salvadó, Mahnaz Shekari, Armand González-Escalante, Marta Milà-Alomà, Anna Brugulat-Serrat, Carolina Minguillon, Matteo Tonietto, Edilio Borroni, Gregory Klein, Clara Quijano-Rubio, Gwendlyn Kollmorgen, Henrik Zetterberg, Kaj Blennow, Juan Domingo Gispert, Oriol Grau-Rivera, Gonzalo Sánchez-Benavides, ALFA study
J Prev Alz Dis 2026;7(13)
Show summaryHide summaryBACKGROUND: The objective of this study was to provide a multimodal biomarker characterization of amnestic objective subtle cognitive decline (obj-SCD) in aging and preclinical Alzheimer’s disease (AD).
METHODS: Prospective observational study; data from the Alzheimer’s and Families+ (ALFAs+) cohort, including cognitively unimpaired (CU) individuals with available baseline CSF biomarkers (normal or AD continuum profiles) and longitudinal neuropsychological assessment (2 time points, 3-year follow-up). Amnestic obj-SCD was defined using robust longitudinal neuropsychological references with multivariate base rate thresholds of significant decline (Free and Cued Selective Reminding Test, Memory Binding Test, Wechsler Memory Scale IV: Logical Memory). Study outcomes included plasma p-tau217, NfL, and GFAP; CSF p-tau181/Aβ42, NfL, and GFAP; Aβ and tau PET; and MRI Grey Matter volume (GMv). The associations of amnestic obj-SCD with fluid (plasma and CSF) and neuroimaging biomarkers (PET and GMv) were evaluated using mixed-effects and voxel-wise linear regression models, respectively.
RESULTS: 350 CU individuals were included (mean age 61 years; 60% female; mean education 14 years; 35% CSF Aβ-positive). Amnestic obj-SCD was identified in 10% of the sample, associated with greater AD pathology (higher plasma p-tau217, CSF p-tau181/Aβ42, global Aβ PET, medial temporal tau PET), neurodegeneration (higher plasma and CSF NfL, reduced GMv in cingulate cortex, longitudinal GMv reductions in hippocampus) and inflammation (higher plasma and CSF GFAP, longitudinal GMv increases in neocortical brain regions).
DISCUSSION: These findings highlight the need for standardized clinical staging criteria to enhance early detection and risk stratification in aging and preclinical AD.
CITATION:
David López-Martos ; Raffaele Cacciaglia ; Marc Suárez-Calvet ; Gemma Salvadó ; Mahnaz Shekari ; Armand González-Escalante ; Marta Milà-Alomà ; Anna Brugulat-Serrat ; Carolina Minguillon ; Matteo Tonietto ; Edilio Borroni ; Gregory Klein ; Clara Quijano-Rubio ; Gwendlyn Kollmorgen ; Henrik Zetterberg ; Kaj Blennow ; Juan Domingo Gispert ; Oriol Grau-Rivera ; Gonzalo Sánchez-Benavides ; ALFA study (2025): Multimodal biomarker characterization of amnestic objective subtle cognitive decline in aging and preclinical Alzheimer’s disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100612
BIOMARKERS IN PRECLINICAL AND EARLY ALZHEIMER’S DISEASE IN CHINA: A SCOPING REVIEW
Guoping Peng, Yan Yang, Ying Wang, Sagar Anil Chandekar, Jintai Yu
J Prev Alz Dis 2026;7(13)
Show summaryHide summaryThis scoping review synthesizes evidence on fluid and neuroimaging biomarkers for preclinical and early Alzheimer’s disease (AD)—including mild cognitive impairment (MCI) and mild AD dementia—in Chinese populations, where a comprehensive overview has been lacking despite AD's increasing biomarker-based definition. We systematically searched four English databases (PubMed, EMBASE, Cochrane, and Web of Science) and three Chinese databases (CNKI, Wanfang, and CQVIP) for studies (2013–2023) reporting diagnostic accuracy of these biomarkers in Chinese preclinical and early AD (eAD) cohorts for clinical use. Due to rapid advancements in biomarker research in China, a supplementary search was conducted in the four English databases for studies published between 2024 and April 30, 2025. Of the 366 included studies investigating fluid or neuroimaging biomarkers in AD, 48 specifically evaluated biomarker performance in biomarker‑confirmed AD populations. Plasma p-tau217 showed strong performance for diagnosing MCI due to AD, and plasma p-tau217, p-tau181/Aβ42, and p-tau217/Aβ42 effectively classified amyloid-β (Aβ) pathology. Multimodal combinations and MRI-based biomarkers also performed well, though evidence is limited. In China, biomarker diagnosis of MCI due to AD is advancing rapidly, while approaches for preclinical AD, machine learning, and multi-protein panels remain in early development.
CITATION:
Guoping Peng ; Yan Yang ; Ying Wang ; Sagar Anil Chandekar ; Jintai Yu (2025): Biomarkers in preclinical and early Alzheimer’s disease in China: a scoping review. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100599
ASSOCIATION BETWEEN OBSTRUCTIVE SLEEP APNEA SEVERITY AND GLYMPHATIC-RELATED DTI-ALPS ALTERATIONS IN NEWLY DIAGNOSED, DRUG-NAÏVE ALZHEIMER’S DISEASE
Wenxue Zheng, Yao Zhou, Yurui Xia, Yiqing Wang
J Prev Alz Dis 2026;7(13)
Show summaryHide summaryBACKGROUND: Obstructive sleep apnea (OSA) is highly prevalent in Alzheimer's disease (AD) patients and is associated with cognitive decline. However, the mechanisms linking OSA to Alzheimer’s pathophysiology, especially regarding glymphatic function, remain unclear. This study investigated the relationship between OSA severity and glymphatic-related diffusion abnormalities, as assessed by the DTI-ALPS index, in newly diagnosed, drug-naïve AD patients.
METHODS: A total of 162 newly diagnosed, drug-naïve AD patients and 98 healthy controls were enrolled. Polysomnography (PSG) was used to assess OSA severity and sleep parameters, while diffusion tensor imaging along the perivascular space (DTI-ALPS) was employed to measure glymphatic function. Correlation analyses, multivariable regression models with interaction terms, and sensitivity analyses were performed to explore the relationship between OSA and glymphatic dysfunction, and whether this relationship was specific to AD.
RESULTS: In AD patients, greater OSA severity was associated with lower ALPS-index values, including AHI (rho = −0.38, P < 0.001) and ODI (rho = −0.35, P < 0.001), whereas these associations were not observed in healthy controls. Lower ALPS-index values were also associated with more fragmented sleep, including higher N1 proportion and arousal index, and with reduced REM sleep. Clinically, the ALPS-index was positively correlated with better cognitive performance on MMSE (rho = 0.28, P = 0.001) and MoCA (rho = 0.31, P < 0.001), and negatively correlated with greater cognitive impairment on ADAS-Cog (rho = −0.34, P < 0.001).
CONCLUSION: Glymphatic dysfunction is related to OSA severity in de novo AD but not in Healthy controls. The study demonstrated that OSA may contribute to neurodegeneration via glymphatic impairment in AD.
CITATION:
Wenxue Zheng ; Yao Zhou ; Yurui Xia ; Yiqing Wang (2025): Association between obstructive sleep apnea severity and glymphatic-related DTI-ALPS alterations in newly diagnosed, Drug-Naïve Alzheimer’s disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100597
VIRTUAL REALITY-BASED TRAINING IN PATIENTS WITH ALZHEIMER\'S DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Junjie Wang, Can Wu, Kedong Zhu, Xiaoshan Qi, Guiqin Chen
J Prev Alz Dis 2026;7(13)
Show summaryHide summaryBACKGROUND AND OBJECTIVES: Prior meta-analyses have suggested that training utilizing virtual reality (VR) serves as a secure and effective intervention for elderly individuals experiencing mild cognitive impairment (MCI). Nevertheless, the effectiveness of such interventions appears to differ among various populations and cognitive domains. Furthermore, there remains a significant gap in understanding the effectiveness of VR-based training, specifically among individuals diagnosed with Alzheimer's disease (AD).
METHODS: The researchers conducted a comprehensive search of databases, including Web of Science, PubMed, Cochrane Library, and EMBASE up until July 1, 2025, focusing on randomized controlled trials that investigated VR-based training in patients diagnosed with AD. The outcomes measured were categorized and analyzed separately, encompassing overall cognitive performance, distinct cognitive domains, psychosocial function, physical capabilities, and the execution of daily living activities within the context of AD trials.
RESULTS: Of the 265 publications identified, 11 (4.15%) randomized controlled trials (RCTs) eventually met all eligibility criteria. Those who received VR-based training showed significantly better global cognitive function [SMD (95%CI) = 0.44 (0.21–0.68)] and Short-term memory [SMD (95%CI) = 0.62 (0.25–0.99)] than the controls. However, no significant improvements were observed in areas such as executive function, spatial memory, activities of daily living, quality of life, balance and coordination, fear of falling, risk of falls, and depression levels.
CONCLUSION: VR-based interventions demonstrated beneficial effects on global cognitive function and short-term memory in AD populations. Due to the small sample size, the current research on evidence for efficacy in people with AD is weak and limited in many indicators.
CITATION:
Junjie Wang ; Can Wu ; Kedong Zhu ; Xiaoshan Qi ; Guiqin Chen (2025): Virtual reality-based training in patients with alzheimer's disease: A systematic review and meta-analysis. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100590
PHENOTYPING OF MILD BEHAVIORAL IMPAIRMENT DOMAINS IN MULTI-REGIONAL DEMENTIA-FREE OLDER ADULTS OF CHINESE ETHNICITY: IMPULSE DYSCONTROL AS THE LEADING DOMAIN
Yingqi Liao, Yaping Zhang, Haoran Zhang, Yan Li, Dylan X. Guan, Yifan Yan, Yuek Ling Chai, Mitchell K.P. Lai, Shifu Xiao, Christopher L.H. Chen, Xin Xu
J Prev Alz Dis 2026;7(13)
Show summaryHide summaryBACKGROUND: Mild behavioral impairment (MBI) is an early neurobehavioral marker of dementia, yet MBI domain patterns remain underexplored among populations of Chinese ethnicity. This study aimed to characterize MBI domain phenotypes by examining the prevalence of MBI domains and identifying the leading domain across multi-regional cohorts of dementia-free older adults of Chinese ethnicity.
METHODS: Data from three previously unpublished datasets (Hangzhou community cohort, China Longitudinal Aging Study and Singapore memory clinic cohort) and three published studies were integrated to estimate the MBI domain prevalence, measured by the Neuropsychiatric Inventory (NPI) and/or MBI-Checklist (MBI-C), through a random-effects meta-analysis. Within the Hangzhou cohort, cross-instrument consistency was evaluated. Exploratory analyses were performed in the Singapore cohort on associations between MBI domains and incident dementia.
RESULTS: Among 1817 participants, impulse dyscontrol was the most prevalent MBI domain, followed by affective dysregulation and decreased motivation, consistently across instruments and cognitive status. In the exploratory longitudinal analyses, impulse dyscontrol was associated with a greater likelihood of incident dementia (HR = 5.05, 95%CI = 2.92 – 8.73).
CONCLUSIONS: Impulse dyscontrol was the leading MBI domain among older adults of Chinese ethnicity, with potential clinical relevance for early identification and dementia risk stratification.
CITATION:
Yingqi Liao ; Yaping Zhang ; Haoran Zhang ; Yan Li ; Dylan X. Guan ; Yifan Yan ; Yuek Ling Chai ; Mitchell K.P. Lai ; Shifu Xiao ; Christopher L.H. Chen ; Xin Xu (2025): Phenotyping of mild behavioral impairment domains in multi-regional dementia-free older adults of Chinese ethnicity: impulse dyscontrol as the leading domain. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100589
INCOME, DIET, AND COGNITIVE FUNCTION: OBSERVATIONAL ANALYSES AND CANDIDATE METABOLOMIC PATHWAYS IDENTIFIED BY MENDELIAN RANDOMIZATION
Xingguang Zhao, Weijian Wu, Qiaoxuan Zhang, Mengqian Ouyang, Haoyu Luo, Qun Yu, Yingren Mai, Zhiyu Cao, Shaoqing Yang, Mingsong Xu, Jun Liu, Wang Liao
J Prev Alz Dis 2026;7(13)
Show summaryHide summaryBACKGROUND: Household income has been shown to have impact on cognitive function, with dietary patterns and gut microbiota–related metabolic pathways potentially acting as mediating pathways. Our study integrates observational analyses and Mendelian randomization (MR) to explore these associations.
METHODS: The observational analysis included 13,457 participants from the UK Biobank who experienced cognitive transitions. A multistate Markov model was applied to assess the effect of income level on cognitive trajectory, while mediation analysis and quantile regression were performed using baseline data. We applied a two-sample, two-step MR approach utilizing genetic instruments from the IEU Open genome-wide association studies (GWAS) project to determine the causal effects of income on cognition, and further estimate the mediating roles of dietary patterns and 1400 gut metabolites linking income with cognitive performance.
RESULTS: Over a median follow-up of 8.96 years, a total of 14,040 cognitive transitions were recorded (7429 deterioration events and 6801 improvements), with higher income associated with a lower risk of cognitive deterioration. MR analyses confirmed a causal relationship between income and cognitive performance (OR: 2.140, 95% CI: 1.923–2.381; P < 0.001). Notably, cheese and coffee intake demonstrated significant mediation effects in both observational and two-way, two-step MR. The protective effect of cheese appeared to be mediated by gut metabolites, particularly via tryptophan/tyrosine and carnitine/ergothioneine.
CONCLUSIONS: Our findings indicate a significant link between income and cognitive performance, cheese and dried fruit may mediate this protective effect through amino acid and carnitine metabolism pathways. Interventions targeting dietary patterns have the potential to prevent cognitive decline attributable to low income.
CITATION:
Xingguang Zhao ; Weijian Wu ; Qiaoxuan Zhang ; Mengqian Ouyang ; Haoyu Luo ; Qun Yu ; Yingren Mai ; Zhiyu Cao ; Shaoqing Yang ; Mingsong Xu ; Jun Liu ; Wang Liao (2025): Income, diet, and cognitive function: observational analyses and candidate metabolomic pathways identified by Mendelian randomization. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100582
THE GROWING BURDEN OF DEMENTIA IN ASIA: COMPARATIVE INSIGHTS FROM JAPAN, CHINA, AND INDIA
Chen Zhang, Xuhui Chen, Yongan Sun
J Prev Alz Dis 2026;7(13)
Show summaryHide summaryBACKGROUND: Alzheimer's disease and other dementias (ADODs) are increasingly becoming a major public health concern in rapidly ageing Asia. We compared the disease burden across Japan, China, and India at different demographic stages.
DESIGN: The Global Burden of Disease Study of 2023 was used to analyze the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) in 1990–2023. Decomposition analysis identified drivers of DALYs trends. DALYs associated risk factors were quantified. The Auto-Regressive Integrated Moving Average model was used to predict future disease burden.
RESULTS: In 2023, China had the highest absolute burden, with age-standardized incidence and prevalence rates of 156.63 (95% uncertainty interval [UI]: 136.58–175.49) and 918.83(95% UI: 784.59–1,058.24) per 100,000, respectively. Japan recorded the highest age-standardized mortality rate (31.25 [8.47–71.42] per 100,000). India had the highest annual increase in mortality and DALYs, with estimated annual percentage changes of 0.91 (95% confidence interval [95% CI] 0.80–1.03) and 0.51 (0.45–0.56), respectively. Decomposition analysis revealed distinct drivers: Japan was dominated by epidemiological changes; China was driven by both aging and epidemiological changes; India was mainly due to population growth and epidemiological changes. Ambient particulate matter was the leading risk factor across all countries, though India faced a unique household air pollution burden. DALYs are predicted to increase in all three countries significantly by 2038.
CONCLUSIONS: The ADODs burden remains substantial, driven by distinct demographic and epidemiological factors in Japan, China, and India. Tailored strategies for prevention and management are essential to address the growing burden.
CITATION:
Chen Zhang ; Xuhui Chen ; Yongan Sun (2025): The growing burden of dementia in Asia: Comparative insights from Japan, China, and India. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100614
LETTER TO THE EDITOR: ASIA’S DEMENTIA BURDEN: FROM EPIDEMIOLOGICAL DESCRIPTION TO PREVENTION-ORIENTED NEUROLOGY
Haoyang Hu
J Prev Alz Dis 2026;7(13)
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CITATION:
Haoyang Hu (2026): Letter to the Editor: Asia’s dementia burden: from epidemiological description to prevention-oriented neurology. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100627
LETTER TO THE EDITOR: CLARITY AD OPEN-LABEL EXTENSION DATA DO NOT ROBUSTLY CONFIRM DISEASE COURSE MODIFICATION BY LECANEMAB IN APOE4 HETEROZYGOTES AND NON-CARRIERS
Jemma Hazan, Kathy Y. Liu, Robert Howard
J Prev Alz Dis 2026;7(13)
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CITATION:
Jemma Hazan ; Kathy Y. Liu ; Robert Howard (2025): Letter to the Editor: Clarity AD open-label extension data do not robustly confirm disease course modification by lecanemab in ApoE4 heterozygotes and non-carriers. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100587
LETTER TO THE EDITOR: CLARITY AD OPEN-LABEL EXTENSION DATA DO NOT ROBUSTLY CONFIRM DISEASE COURSE MODIFICATION BY LECANEMAB IN APOE4 HETEROZYGOTES AND NON-CARRIERS
Lutz Froelich
J Prev Alz Dis 2026;7(13)
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CITATION:
Lutz Froelich (2025): Letter to the editor: Clarity AD open-label extension data do not robustly confirm disease course modification by lecanemab in ApoE4 heterozygotes and non-carriers. # TJPAD-D-26-00165. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100588
EDITORIAL: WELCOME TO CTAD25 IN SAN DIEGO!
Paul Aisen
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CITATION:
Paul Aisen (2026): Editorial: Welcome to CTAD25 in San Diego!. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100616
18TH CONFERENCE CLINICAL TRIALS ALZHEIMER’S DISEASE DECEMBER 1-4, 2025, SAN DIEGO, CA (UNITED STATES) - CONFERENCE PROCEEDINGS
SYMPOSIA, ORAL COMMUNICATIONS
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https://doi.org/10.1016/j.tjpad.2026.100617
OPEN ACCESS18TH CONFERENCE CLINICAL TRIALS ALZHEIMER’S DISEASE DECEMBER 1-4, 2025, SAN DIEGO, CA (UNITED STATES) - CONFERENCE PROCEEDINGS
POSTERS
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https://doi.org/10.1016/j.tjpad.2026.100618
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