09/2026 journal articles
EDITORIAL: OPPORTUNITIES TO TREAT SPECIFIC POPULATIONS WITH REPURPOSED DRUGS
Serge Gauthier
J Prev Alz Dis 2026;9(13)
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CITATION:
Serge Gauthier: Editorial: Opportunities to treat specific populations with repurposed drugs. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.1016/j.tjpad.2026.100671
EDITORIAL: WHAT\'S GOOD FOR THE HEART IS GOOD FOR THE BRAIN? EVIDENCE FROM A RURAL COHORT ON THE LONGITUDINAL RELATIONSHIP BETWEEN ATHEROSCLEROTIC CARDIOVASCULAR DISEASE RISK AND COGNITIVE DECLINE
Maileen G. Ulep
J Prev Alz Dis 2026;9(13)
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CITATION:
Maileen G. Ulep: Editorial: What's good for the heart is good for the brain? Evidence from a rural cohort on the longitudinal relationship between atherosclerotic cardiovascular disease risk and cognitive decline. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.1016/j.tjpad.2026.100672
EDITORIAL: FROM ADVICE TO AGENCY: MAKING BRAIN HEALTH ACTIONABLE AND EQUITABLE FOR MIDDLE-AGED ADULTS WITH MILD NEUROCOGNITIVE DISORDER
Hermine Lenoir
J Prev Alz Dis 2026;9(13)
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CITATION:
Hermine Lenoir: Editorial: From advice to agency: making brain health actionable and equitable for middle-aged adults with mild neurocognitive disorder. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.1016/j.tjpad.2026.100667
FRAILTY IN THE ANTI-AMYLOID ERA: AN OPPORTUNITY TO INDIVIDUALIZE CARE
Nicholas M. Vogt, Dae Hyun Kim
J Prev Alz Dis 2026;9(13)
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CITATION:
Nicholas M. Vogt ; Dae Hyun Kim (2026): Editorial: Frailty in the anti-amyloid era: an opportunity to individualize care. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.1016/j.tjpad.2026.100682
RISK OF DEMENTIA AFTER INITIATION OF GLP-1 RA VERSUS LONG-ACTING INSULIN IN PATIENTS WITH TYPE 2 DIABETES MELLITUS
Chien-Hung Lin, Peir-Haur Hung, Mu-Chi Chung, Laing-You Wu, Chi-Jung Chung
J Prev Alz Dis 2026;9(13)
Show summaryHide summaryBACKGROUND: Recent studies suggest a decreased risk of dementia in patients treated with glucagon-like peptide-1 receptor agonist (GLP-1 RA). In this study, we compare the risk of dementia associated with GLP-1 RA versus long-acting insulin in adults aged over 50 years with type 2 diabetes (T2DM) using real-world administrative data from a large Taiwan cohort
DESIGN: A population-based retrospective cohort study
SETTING: We analyzed 10,783 propensity score-matched pairs of adults with T2DM who initiated either GLP-1 RA or long-acting insulin from Taiwan's National Health Insurance Research Database (2011-2021).
MEASUREMENTS: Primary outcome was new-onset dementia; secondary outcomes included dementia requiring treatment and specific dementia subtypes (Alzheimer's disease, vascular dementia, and unspecified dementia). Hazard ratios (HRs) were estimated using Cox models. Results: Analysis of matched pairs identified 375 cases of newly diagnosed dementia. The incidence rate was 4.86 per 1,000 person-years in GLP-1 RA users versus 7.56 in insulin users. GLP-1 RA use was associated with significantly lower risk of overall dementia (HR 0.64, 95% CI 0.46-0.89, P=0.0072) and unspecified dementia (HR 0.41, 95% CI 0.24-0.68, P=0.0006), but not for Alzheimer's disease (HR 1.48, 95% CI 0.61-3.63, P=0.3867) or vascular dementia (HR 1.66, 95% CI 0.21-13.03, P=0.6324). Among GLP-1 RAs, both liraglutide (HR 0.40, 95% CI 0.20-0.80, P=0.0091) and dulaglutide (HR 0.42, 95% CI 0.19-0.92, P=0.0311) showed significant protective effects against unspecified dementia.
CONCLUSIONS: GLP-1 RA use was associated with lower dementia risk versus long-acting insulin in T2DM patients, especially with liraglutide and dulaglutide. As observational, causality requires confirmation from randomized controlled trials.
CITATION:
Chien-Hung Lin ; Peir-Haur Hung ; Mu-Chi Chung ; Laing-You Wu ; Chi-Jung Chung (2026): Risk of Dementia after initiation of GLP-1 RA versus long-acting insulin in patients with type 2 Diabetes mellitus. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100645
INCREASING CARDIOVASCULAR DISEASE RISK PREDICTS FASTER COGNITIVE DECLINE: A BAYESIAN ANALYSIS OF A COHORT OF ADULTS IN RURAL WEST TEXAS
Chathurika S. Dhanasekara, Chanaka N. Kahathuduwa, Chanaka N. Kahathuduwa
J Prev Alz Dis 2026;9(13)
Show summaryHide summaryBACKGROUND: Cardiovascular disease (CVD) is a major risk factor for cognitive decline and dementia. We examined whether a higher atherosclerotic cardiovascular disease (ASCVD) risk is associated with faster cognitive decline in Project FRONTIER, a rural cohort.
METHODS: Participants were aged ≥40 years without baseline CVD and completed two study visits. Primary outcomes were the RBANS Total Score and its domains; secondary outcomes were Executive Interview 25, verbal fluency, Clock Drawing Test (CLOX), and Trail Making Test (TMT) A and B. Primary exposure was the 10-year ASCVD risk per AHA PREVENT equations. We fitted Bayesian mixed-effects models to estimate the interaction between time (in years) and ASCVD risk, adjusting for covariates using brms package in R.
RESULTS: We analyzed data of 383 participants (age 57.74 ± 11.4 years; 75.5 % female; 59.8 % Hispanic; median follow-up 3.00 years, IQR: 2.67–3.64). The time×ASCVD risk interaction for RBANS Total was credibly negative (β = −1.22 points/year per 10 % higher risk, 95 % CrI −1.87 to −0.58). Strongest domain-specific effects were for attention (β = −1.25; 95 % CrI −2.14 to −0.37) and delayed memory (β = −1.36; 95 % CrI −2.16 to −0.05). CLOX suggested a credibly negative interaction (β = −0.39; 95 % CrI −0.62 to −0.16), and TMT-A showed a credibly positive interaction (β = +2.85 s/year; 95 % CrI 1.28 to 4.41).
DISCUSSION: In this rural cohort, a higher 10-year ASCVD risk was associated with faster decline in global cognition, particularly attention and delayed memory, supporting the potential value of cardiovascular risk monitoring and modification to preserve cognitive function.
CITATION:
Chathurika S. Dhanasekara ; Chanaka N. Kahathuduwa ; Volker Neugebauer (2026): Increasing cardiovascular disease risk predicts faster cognitive decline: A Bayesian analysis of a cohort of adults in rural West Texas. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100651
BRAIN HEALTH STRATEGIES IN MIDDLE-AGED INDIVIDUALS WITH MILD NEUROCOGNITIVE DISORDER: A SCOPING REVIEW
Joshi Dookhy, Yvonne McCague, Jim Hickson, Diarmuid Stokes, Thilo Kroll, Kate Frazer
J Prev Alz Dis 2026;9(13)
Show summaryHide summaryBrain health refers to optimal brain functioning and integrity, shaped by complex cognitive, psychological, and social determinants. Individuals with mild neurocognitive disorder (mNCD) are at higher risk of developing dementia. Prioritising brain health is essential throughout the lifespan, particularly at midlife when health risks often emerge alongside heavy life responsibilities. International frameworks emphasise addressing modifiable risk factors across the lifespan to reduce dementia risk, yet little is known about the strategies middle-aged individuals with mNCD use to maintain brain health in everyday life. Understanding how people in midlife interpret and act on information about brain health is essential to align clinical care and prevention policies with lived experience. This scoping review followed the Joanna Briggs Institute methodology and mapped data published from August 2015 to 2025 using the 2024 Lancet Commission on dementia and the Cochrane PROGRESS-Plus equity framework. The primary aim of this review was to map the range and characteristics of non-pharmacological brain health strategies used by middle-aged individuals with mNCD to reduce the risks of developing dementia. After screening 6349 records, 17 articles were included. The results are presented in three groups: brain health strategies, facilitators and barriers across strategies, and the equity analysis. Strategies were classified as formalised interventions and self-directed practices. Facilitators and barriers varied according to population characteristics and the strategies used. Equity gaps included limited representation of study participants from rural and low-socioeconomic settings, reduced generalisability to male populations, and underrepresentation of minoritised ethnic groups. Clinicians, service planners, and policymakers should prioritise equity-oriented brain health strategies co-designed with middle-aged individuals. Equity and co-design should be explicitly integrated within global brain health policies and agendas.
CITATION:
Joshi Dookhy ; Yvonne McCague ; Jim Hickson ; Diarmuid Stokes ; Thilo Kroll ; Kate Frazer (2026): Brain health strategies in middle-aged individuals with mild neurocognitive disorder: a scoping review. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100657
INTEGRATING FRAILTY INTO DECISION-MAKING FOR DISEASE-MODIFYING THERAPIES IN ALZHEIMER’S DISEASE: A PROPOSED EXPERT-OPINION BASED APPROACH
Giuseppe Bellelli, Ovidio Brignoli, Marco Canevelli, Antonio Cherubini, Maria Cristina Ferrara, Laura Fratiglioni, Giovanni B. Frisoni, Giulia Grande, Alberto Magni, Martina Marelli, Alessandra Marengoni, Nicolás Martínez Velilla, Marc Suárez-Calvet, Suzanne Timmons, Alessandro Padovani
J Prev Alz Dis 2026;9(13)
Show summaryHide summaryThe introduction of disease-modifying therapies for Alzheimer’s disease (AD-DMTs) is reshaping clinical practice, raising critical questions about patient selection, diagnostic pathways, treatment appropriateness, and equity of access. Frailty, a multidimensional condition of reduced physiological reserve and increased vulnerability to stressors, is common in older adults with AD, yet has not been systematically assessed in AD-DMTs trials, limiting the generalizability of trial findings to real-world populations.
In this review, we examine the role of frailty in the emerging era of AD-DMTs, summarizing evidence on its prevalence and prognostic relevance, approaches to its assessment, and its potential impact on treatment safety and effectiveness. We propose that regular frailty assessment should inform decision-making in both clinical trials and clinical practice, while frailty-informed management—including medication review and multidomain interventions—may support more appropriate, individualized care.
CITATION:
Giuseppe Bellelli ; Ovidio Brignoli ; Marco Canevelli ; Antonio Cherubini ; Andrew Clegg ; Bruno Dubois ; Maria Cristina Ferrara ; Laura Fratiglioni ; Giovanni B. Frisoni ; Giulia Grande ; Frank Jessen ; Sean P Kennelly ; Alberto Magni ; Martina Marelli ; Alessandra Marengoni ; Nicolás Martínez Velilla ; Susan D. Shenkin ; Marc Suárez-Calvet ; Suzanne Timmons ; Alessandro Padovani: Integrating frailty into decision-making for disease-modifying therapies in Alzheimer’s disease: a proposed expert-opinion based approach. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.1016/j.tjpad.2026.100666
COMPREHENSIVE SOCIAL DETERMINANTS OF HEALTH AND BRAIN HEALTH IN MIDLIFE
Christina S. Dintica, Julia Cheunkarndee, R. Nick Bryan, Lenore J. Launer, Kristine Yaffe
J Prev Alz Dis 2026;9(13)
Show summaryHide summaryBACKGROUND: Social determinants of health (SDOH) are increasingly recognized as important drivers of cognitive outcomes. However, most existing evidence focuses on individual SDOH components and older populations.
OBJECTIVES: To develop a comprehensive SDOH index and examine its association with subsequent changes in cognitive function and structural brain measures in midlife.
DESIGN: Prospective cohort study with repeated measures of cognition and brain imaging.
SETTING: Community-based cohort from the Coronary Artery Risk Development in Young Adults (CARDIA) study.
PARTICIPANTS: A total of 3488 participants with SDOH data in early midlife (mean age 40.0 ± 3.6 years); 645 participants had repeated brain magnetic resonance imaging (MRI) data.
MEASUREMENTS: A weighted aggregate SDOH index was constructed from 12 items across 5 domains: economic stability, community and social context, education, neighborhood and built environment, and health care access. Cognitive function was assessed using the Digit Symbol Substitution Test (DSST), Stroop Test, and Rey Auditory Verbal Learning Test (RAVLT). Brain MRI outcomes included white matter hyperintensities (WMHs) and total gray matter (GM) volume. Mixed linear regression models examined associations between SDOH quartiles and longitudinal cognitive and MRI outcomes, adjusting for demographics, vascular risk factors, depression, and intracranial volume (for MRI).
RESULTS: At baseline, participants in the most disadvantaged SDOH quartile performed worse across all cognitive tests compared with the least disadvantaged quartile (p < 0.001). Over time, the most disadvantaged quartile showed steeper decline in DSST performance (adj. mean change: −0.72, 95% CI: −0.93 to −0.52 vs. −0.55, 95% CI: −0.76 to −0.34, p = 0.013), greater WMH accumulation (ratio: 1.07, 95% CI: 1.05 to 1.09 vs. 1.04, 95% CI: 1.03 to 1.05, p = 0.007), and steeper decline in total GM volume (−2.02 cm³, 95% CI: −2.39 to −1.65 vs. −1.46 cm³, 95% CI: −1.71 to −1.20, p = 0.011) per 5-year interval compared to the least disadvantaged quartile.
CONCLUSIONS: Greater social disadvantage in midlife is associated with worse baseline cognition and accelerated decline in cognitive function and brain integrity. These findings highlight the importance of SDOH as key determinants of brain health in midlife and suggest that strategies to mitigate social disadvantage may help preserve cognitive and brain health.
CITATION:
Christina S. Dintica ; Julia Cheunkarndee ; R. Nick Bryan ; Lenore J. Launer ; Kristine Yaffe (2026): Comprehensive social determinants of health and brain health in midlife. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100652
THE MISSING IMPROVERS: TAU PATHOLOGY, NEUROPLASTICITY, AND THE CASE FOR TAU-INFORMED PATIENT SELECTION BEFORE AMYLOID IMMUNOTHERAPY
Eric Dinnerstein
J Prev Alz Dis 2026;9(13)
Show summaryHide summaryAmyloid immunotherapy with lecanemab and donanemab has been approved on the basis of statistically significant slowing of cognitive and functional decline in early Alzheimer's disease (1,2). Yet clinicians treating individual patients face the everyday challenge of estimating whether a given patient is declining at the rate that would be expected for them, and whether their trajectory reflects a response to treatment. I argue that this difficulty arises in large part because the field cannot yet routinely stratify patients by tau pathology before treatment, even though tau burden is among the strongest available predictors of both the rate of progression and the magnitude of response to amyloid-targeting therapy. Post-hoc and open-label analyses of the Clarity AD and TRAILBLAZER-ALZ 2 programmes suggest that patients with absent, low, or medium tau burden may constitute a biologically distinct group in whom amyloid clearance is most likely to permit clinical stabilization or measurable functional gain. These observations remain hypotheses, generated largely from subgroup, open-label, and biomarker data rather than from prospective trials designed to test them I propose that tau status should be given strong consideration in patient selection, that tau-guided selection should be evaluated prospectively, and that the access, reimbursement, and standardization barriers to tau positron emission tomography (PET) — together with the promise of scalable plasma tau biomarkers — be addressed deliberately as the field moves toward tau-informed treatment. One tau PET tracer is currently approved by the US Food and Drug Administration, and a regulatory decision on a second is anticipated in 2026.
CITATION:
Eric Dinnerstein (2026): The missing improvers: Tau pathology, neuroplasticity, and the case for tau-informed patient selection before amyloid immunotherapy. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100653
REAL-WORLD LONG-TERM CONTINUATION OF LECANEMAB THERAPY AND THE CLINICAL UTILITY OF PHOSPHORYLATED TAU 181
Moeko Noguchi-Shinohara, Daiki Muramatsu, Ayano Shima, Yasuhiro Sakashita, Junji Komatsu, Tokuhei Ikeda, Kenjiro Ono
J Prev Alz Dis 2026;9(13)
Show summaryHide summaryThis real-world study evaluated the long-term feasibility of lecanemab treatment in 117 patients with early Alzheimer's disease at Kanazawa University Hospital. To assess treatment persistence over a full 18-month course, we focused on the 64 patients who initiated treatment between January and December 2024. Of these 64 patients, 78.1% completed the full 18-month course, and all 48 eligible patients elected to continue beyond 18 months. The overall discontinuation rate was 21.9%, with amyloid-related imaging abnormalities (ARIA) (27.7%), decreased motivation (22.2%), and cognitive decline (11.1%) as the primary reasons. Among all 117 patients, ARIA occurred in 12.9% and was significantly associated with apolipoprotein Eε4 carrier status, elevated baseline cerebrospinal fluid (CSF)-phosphorylated tau (ptau) 181 (ptau181; ≥78.6 pg/ml), ≥2 microbleeds, and Fazekas score≥2 deep white matter hyperintensity. Elevated CSF-ptau181 also independently predicted cognitive decline during treatment and ARIA-related discontinuation. These findings suggest that integrating CSF-ptau181 measurement and baseline MRI into clinical decision-making may support individualized risk stratification and the safe, sustained use of lecanemab in real-world practice.
CITATION:
Moeko Noguchi-Shinohara ; Daiki Muramatsu ; Ayano Shima ; Yasuhiro Sakashita ; Yasutake Tada ; Hiroki Yamaguchi ; Junji Komatsu ; Tokuhei Ikeda ; Kenjiro Ono ; ; (): Real-world long-term continuation of lecanemab therapy and the clinical utility of phosphorylated tau 181. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.1016/j.tjpad.2026.100664
RELATIVE IMPORTANCE OF BLOOD-BASED BIOMARKERS FOR ALZHEIMER’S DISEASE-SPECIFIC NEURODEGENERATION AND COGNITIVE DECLINE
Keun You Kim, Hyunsun Ham, Eun Jin Yoon, Eosu Kim, Yu Kyeong Kim, Jun-Young Lee, Alzheimer’s Disease Neuroimaging Initiative
J Prev Alz Dis 2026;9(13)
Show summaryHide summaryBACKGROUND: Although blood-based biomarkers are now available for diagnosing Alzheimer’s disease (AD), the best biomarker for AD-specific neurodegeneration and cognitive decline remains unclear. This study aimed to determine the relative importance of four plasma biomarkers—phosphorylated tau (p-tau) 217, p-tau181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP)—in AD-specific neurodegeneration and cognition.
METHODS: We analyzed cross-sectional data from two independent, ethnically distinct cohorts spanning the clinical spectrum from cognitively unimpaired to dementia: 150 participants from the SAMD cohort (100% Asian) and 284 participants from the ADNI cohort (94.0% White). Plasma biomarker levels were quantified using Single-Molecule Array (Simoa) assays. We employed dominance analysis to determine the hierarchical contributions of these biomarkers to AD signature regions of interest (ROI) thickness (entorhinal, inferior temporal, middle temporal, and fusiform regions), total cognition, and memory, stratified by amyloid-PET status. Three sensitivity analyses were further conducted to validate the findings across these cohorts, mitigating potential biases arising from differences in demographic characteristics and clinical severity. All analyses were adjusted for age, sex, education, and APOE ε4 status.
RESULTS: The dominance hierarchy differed markedly according to the amyloid status. Plasma GFAP and p-tau217 emerged as the dominant predictors for AD signature ROI thickness and cognitive impairment in amyloid-positive participants. Specifically, GFAP demonstrated superior dominance in explaining cortical atrophy within the SAMD cohort, whereas p-tau217 was the dominant predictor in the ADNI cohort. P-tau217 generally outperformed the others in explaining total cognition and memory in the amyloid (+) group. In contrast, among amyloid (−) participants, plasma NfL showed greater explanatory power than GFAP for both neurodegeneration and cognitive decline across both cohorts.
CONCLUSION: The efficacy of plasma biomarkers in reflecting AD-related neurodegeneration varies significantly depending on the presence of amyloid pathology. While GFAP and p-tau217 are robust indicators of AD-associated changes linked to plaque pathology, NfL better reflects non-specific neurodegeneration involving axonal damage. Consequently, a stratified approach based on amyloid status is essential for the optimal application of blood-based biomarkers in monitoring disease progression and evaluating therapeutic efficacy in future clinical trials and precision medicine.
CITATION:
Keun You Kim ; Hyunsun Ham ; Eun Jin Yoon ; Eosu Kim ; Yu Kyeong Kim ; Jun-Young Lee ; Alzheimer’s Disease Neuroimaging Initiative (2026): Relative importance of blood-based biomarkers for Alzheimer’s disease-specific neurodegeneration and cognitive decline. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100644
PSYCHOLOGICAL ADVERSITIES AND EPIGENETIC AGEING IN MIDLIFE AND OLDER AGE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Jiuyu Guo, Jiatong Shan, Kaisy Xinhong Ye, Wei Liang, Yanyu Wang, Eng-Tat Ang, Tih-Shih Lee, John Suckling, Andrea B. Maier, Lei Feng
J Prev Alz Dis 2026;9(13)
Show summaryHide summaryBACKGROUND: Epigenetic modification is a hallmark of aging that encloses physiological information relevant to health and longevity and has been used to construct epigenetic clocks that estimate epigenetic age acceleration (EAA) to monitor population health across the life span. Psychological adversities (PA) are recognized contributors to poor health; however, their potential role in EAA remains insufficiently understood in older adults.
OBJECTIVE: This study systematically reviews and meta-analyzes the association between PA and EAA from midlife onward.
METHODS: Eligible literatures were indexed in five databases up to July 2025. Study quality was assessed using an adapted Newcastle-Ottawa scale. Meta-analyses were performed using random-effects models, followed by post hoc and sensitivity analyses to assess robustness.
RESULTS: Twenty-two studies were included, of which fifteen were classified as high quality. Irrespective of the type of psychological adversity, positive associations were consistently observed for second-generation epigenetic clocks (PhenoAge and GrimAge). Meta-analyses revealed that greater loneliness (β = 0.07, 95 % CI [0.06, 0.08], I2 = 0 %, p = 0.002), depression (β = 0.08, 95 % CI [0.04, 0.13], I2 = 55.2 %, p = 0.003), and stress (β = 0.10, 95 % CI [0.03, 0.16], I2 = 68.4 %, p = 0.009) were each associated with higher EAA.
CONCLUSIONS: Psychosocial stress, depression, and loneliness are each associated with accelerated aging from midlife onward. Notable gaps include the lack of studies examining anxiety and underrepresentation of non-Western population. Whether alleviating psychological adversities translates into decelerated aging trajectories requests future intervention studies.
CITATION:
Jiuyu Guo ; Jiatong Shan ; Kaisy Xinhong Ye ; Wei Liang ; Yanyu Wang ; Eng-Tat Ang ; Tih-Shih Lee ; John Suckling ; Andrea B. Maier ; Lei Feng (2026): Psychological adversities and epigenetic ageing in midlife and older age: A systematic review and meta-analysis. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100650
TIMING OF COGNITIVE DECLINE ONSET AND LIFE-COURSE TRAJECTORIES A POOLED LONGITUDINAL ANALYSIS OF 14,389 ADULTS ACROSS THREE COHORTS
Jan Sebastian Novotný, Sivan Klil-Drori, Yonas Endale Geda, Ziad Nasreddine, Gorazd Bernard Stokin
J Prev Alz Dis 2026;9(13)
Show summaryHide summaryBACKGROUND: Population ageing is driving a global surge in cognitive impairment. While late-life decline is well-characterized, the onset of measurable cognitive changes across the full adult lifespan remains uncertain. We aimed to estimate the age at which detectable decline begins using longitudinal data from three population-based cohorts from three countries spanning three continents.
METHODS: We analyzed participant-level longitudinal data from the China Health and Retirement Longitudinal Study (CHARLS; China), Midlife in the United States (MIDUS; USA), and Kardiovize (KV; Czech Republic). Cognitive performance was assessed using validated instruments (TICS, BTACT, and MoCA). Scores were harmonized using the percent of maximum possible method (0-100 metric). Linear mixed-effects models, adjusted for age group, sex, and education estimated change over an average 7–9-year follow-up.
FINDINGS: In pooled sample of 14,389 participants (baseline age 22-94 years), a detectable decline in total cognition first emerged in the 31-40 age group (mean change -1.2 points, 95% CI -2.1 to -0.3). Decline magnitude increased progressively with age, reaching -11.4-points in the oldest strata (all p<0.001). Non-memory domains showed earlier vulnerability (detectable from age 31), while significant memory decline emerged after age 50. Individual trajectories showed substantial heterogeneity, suggesting that chronological age is not a deterministic proxy for decline.
INTERPRETATION: Population-level cognitive decline became detectable in early midlife, decades before the traditional clinical focus on older age. Across three population-based cohorts from Asia, North America, and Europe, we observed consistent early decline in non-memory domains followed by later memory decline. These findings support evaluation of midlife cognitive monitoring and life-course approaches to brain health.
CITATION:
Jan Sebastian Novotný ; Sivan Klil-Drori ; Yonas Endale Geda ; Ziad Nasreddine ; Gorazd Bernard Stokin (2026): Timing of cognitive decline onset and life-course trajectories A pooled longitudinal analysis of 14,389 adults across three cohorts. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100649
COST-EFFECTIVENESS OF THE SPECIAL CARE UNIT FOR PERSONS WITH DEMENTIA
Ron Handels, Bernhard Michalowsky, Aline Mendes, Sverre Bergh, Bruno Mario Cesana, Alfonso Ciccone, Emmanuel Cognat, Andrea Fabbo, Sara Fascendini, Giovanni B. Frisoni, Lutz Froelich, Patrizia Mecocci, Paola Merlo, Oliver Peters, Magdalini Tsolaki, Carlo Alberto Defanti, RECage consortium collaborators
J Prev Alz Dis 2026;9(13)
Show summaryHide summaryINTRODUCTION: We aimed to estimate the cost-effectiveness of the patient-centered special care unit for behavioral and psychological symptoms of dementia (SCU-B) in the Respectful Caring for the Agitated Elderly (RECage) study.
METHODS: A health-economic evaluation was performed alongside a controlled European multicenter three-year longitudinal cohort study enrolling 508 participants in a non-SCU-B cohort and SCU-B cohort. Health service resource use, costs, quality-adjusted life years (QALYs), and incremental cost per QALY gained were assessed.
RESULTS: Total QALYs were lower (−0.13; bootstrap-interval −0.23 to −0.02) and total costs were higher (€24,960; bootstrap-interval 14,870 to 35,090) in the SCU-B cohort. Base case and sensitivity analyses indicated the SCU-B was likely not cost-effective.
DISCUSSION: Widespread implementation as well as disinvestment of SCU-B cannot be recommended, given the uncertainty of the study results. We recommend a randomized study stratified by (local/county) region for conclusive evidence.
CITATION:
Ron Handels ; Bernhard Michalowsky ; Aline Mendes ; Sverre Bergh ; Bruno Mario Cesana ; Alfonso Ciccone ; Emmanuel Cognat ; Andrea Fabbo ; Sara Fascendini ; Giovanni B. Frisoni ; Lutz Froelich ; Patrizia Mecocci ; Paola Merlo ; Oliver Peters ; Magdalini Tsolaki ; Carlo Alberto Defanti ; RECage consortium collaborators (2026): Cost-effectiveness of the special care unit for persons with dementia. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100647
QUANTIFYING GENERALIZATION ERROR IN MACHINE LEARNING PREDICTION OF COGNITIVE DECLINE
Roya Melanie Hüppi, Nicolas Langer, Bruno Hebling Vieira, for the Alzheimer’s Disease Neuroimaging Initiative
J Prev Alz Dis 2026;9(13)
Show summaryHide summaryBACKGROUND: Predicting cognitive decline as a continuum, from healthy age-related decline to mild cognitive impairment and dementia, enables more precise individual-level predictions. However, the practical value of such models for early intervention and prevention depends on their ability to generalize to independent cohorts, a property that is often not evaluated.
OBJECTIVES: This study investigated whether adding structural magnetic resonance imaging (MRI) to non-brain data improved machine learning predictions of continuous cognitive decline and analyzed the models’ generalizability.
DESIGN: Multi-target random forest regression models predicted annual decline in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) and Mini-Mental State Examination (MMSE) using non-brain data, structural MRI data, or their combination from the Alzheimer's Disease Neuroimaging Initiative (ADNI; N = 1237) and Open Access Series of Imaging Studies (OASIS-3; N = 662) datasets. Cross-site generalizability was evaluated.
SETTING: Data from ADNI and OASIS-3 were used for this study.
PARTICIPANTS: A total of 1899 participants who had demographic, clinical, and brain imaging data from a baseline session and clinical data from at least 2 follow-up sessions were included.
MEASUREMENTS: Baseline non-brain (demographics, clinical and neuropsychological scores, information on APOE genotype, cognitive diagnosis, health, and number of sessions before baseline) and/or structural MRI data were used to predict the yearly rate of change in CDR-SOB and MMSE scores.
RESULTS: Including structural MRI data improved prediction of CDR-SOB and MMSE change, reaching respective R2 values of .41 and .33 in ADNI and .42 and .33 in OASIS-3. Model performance for across-dataset predictions was reduced (R2 between .18 and .35), unexplained by distributional shifts of target variables. Models using only top predictive features performed similarly to full models when tested externally (R2 between .18 and .34), suggesting predictor redundancy.
CONCLUSIONS: Incorporating structural MRI data enhances within-dataset prediction of continuous cognitive decline, allowing for more precise individual-level prediction and advancing towards precision medicine. Even though external validation remains limited, quantifying the generalizability gap is a crucial step towards the responsible use of ML models in clinical intervention and prevention.
CITATION:
Roya Melanie Hüppi ; Nicolas Langer ; Bruno Hebling Vieira ; for the Alzheimer’s Disease Neuroimaging Initiative (2026): Quantifying generalization error in machine learning prediction of cognitive decline. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100646
CHOROID PLEXUS VOLUME IN PATHOLOGY-CONFIRMED ALZHEIMER\'S DISEASE
Francis Fernandes, Avyarthana Dey, Andy Ma, Nathan W. Churchill, Corinne E. Fischer, Simon J. Graham, David G. Munoz, Tom A. Schweizer
J Prev Alz Dis 2026;9(13)
Show summaryHide summaryINTRODUCTION: The choroid plexus (CP) increases in volume across the Alzheimer’s disease (AD) continuum, suggesting its potential as a clearance-related biomarker. However, few studies have examined ante-mortem CP volume in relation to post-mortem AD pathology, the gold standard for diagnosis.
METHODS: Participants who had structural magnetic resonance imaging and post-mortem pathology, with an interval of ≤ 5 years between imaging and death, were examined. Normalized CP volume (NCPV) was semi-automatically segmented from the lateral ventricles and analyzed using Bayesian linear regression to estimate associations with cognitive impairment (CI), AD pathology, and relevant clinical/demographic data.
RESULTS: Intermediate and high levels of AD pathology and CI were associated with larger NCPV, whereas female sex was associated with lower NCPV. Subgroup analyses showed larger NCPV in individuals with greater CI despite comparable levels of AD pathology.
DISCUSSION: These findings link CP enlargement to neuropathologically confirmed AD burden and CI, supporting further investigation of CP structure and function in AD.
CITATION:
Francis Fernandes ; Avyarthana Dey ; Andy Ma ; Nathan W. Churchill ; Corinne E. Fischer ; Simon J. Graham ; David G. Munoz ; Tom A. Schweizer (2026): Choroid plexus volume in pathology-confirmed Alzheimer's disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100648
PREDICTIVE VALUE OF THE ALZHEIMER POLYGENIC RISK SCORE ON COGNITIVE DECLINE IN PATIENTS WITH MILD COGNITIVE IMPAIRMENT AND ALZHEIMER\'S DISEASE DEMENTIA
Berta Calm, Adrián Hinojosa-Calleja, Fernando García-Gutiérrez, Josep Blazquez-Folch, Montserrat Alegret, Maria Victoria Fernández, Itziar De Rojas, Pablo García-González, Clàudia Olivé, Alejandro Valenzuela-Seba, Paula Bayón-Buján, Amanda Cano, Raquel Puerta, Maria Capdevila-Bayo, Álvaro Muñoz-Morales, Andrea Miguel, Ariadna Solivar, Laura Montrreal, Pilar Sanz-Cartagena, Maitee Rosende-Roca, Yahveth Cantero-Fortiz, Miren Jone Gurruchaga, Lluís Tárraga, Mercè Boada, Marta Marquié, Agustín Ruiz, Sergi Valero, for theAlzheimer’s Disease Neuroimaging Initiative
J Prev Alz Dis 2026;9(13)
Show summaryHide summaryBACKGROUND: Polygenic risk scores for Alzheimer’s disease (AD-PRS) are widely used to estimate genetic susceptibility to AD, but their relationship with the rate of cognitive decline (CD) after clinical onset remains insufficiently characterized.
OBJECTIVES: To examine the association between AD-PRS and longitudinal CD across the AD spectrum and to evaluate the predictive contribution of individual AD-PRS variants.
DESIGN: Large longitudinal observational study in a single-center cohort, with an external cohort to assess generalizability.
SETTING: Memory clinic cohort from Ace Alzheimer Center Barcelona (Ace) with external cohort using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI).
PARTICIPANTS: The study included 7,233 patients from Ace and 863 from ADNI, with a mean follow-up of 5.4 years in Ace and 3.6 years in ADNI. A biomarker sub-cohort included 1075 participants from Ace and 569 from ADNI.
MEASUREMENTS: CD was quantified as the annual change in Mini-Mental State Examination (MMSE) scores estimated using linear mixed-effects models. Associations between AD-PRS and longitudinal MMSE trajectories were tested adjusting for clinical and sociodemographic (CSD) variables and APOE genotype. Machine learning models and SHapley Additive exPlanations (SHAP) were used to evaluate the predictive relevance of individual variants.
RESULTS: Higher AD-PRS was associated with faster CD in the full clinical cohort and in biomarker subset, independently of APOE genotype. AD-PRS was not associated with baseline MMSE. APOE ε4 was associated with lower baseline MMSE and faster CD only in the full clinical sample. Genetic predictors provided limited improvement beyond CSD variables, and model performance showed limited reproducibility across cohorts.
CONCLUSIONS: AD-PRS is associated with longitudinal CD across the AD spectrum. Although polygenic burden contributes to variability in cognitive trajectories, its added predictive value beyond routinely available clinical variables remains modest.
CITATION:
Berta Calm ; Adrián Hinojosa-Calleja ; Fernando García-Gutiérrez ; Josep Blazquez-Folch ; Montserrat Alegret ; Maria Victoria Fernández ; Itziar De Rojas ; Pablo García-González ; Clàudia Olivé ; Alejandro Valenzuela-Seba ; Paula Bayón-Buján ; Amanda Cano ; Raquel Puerta ; Maria Capdevila-Bayo ; Álvaro Muñoz-Morales ; Andrea Miguel ; Ariadna Solivar ; Laura Montrreal ; Pilar Sanz-Cartagena ; Maitee Rosende-Roca ; Yahveth Cantero-Fortiz ; Miren Jone Gurruchaga ; Lluís Tárraga ; Mercè Boada ; Marta Marquié ; Agustín Ruiz ; Sergi Valero ; for theAlzheimer’s Disease Neuroimaging Initiative (2026): Predictive value of the Alzheimer polygenic risk score on cognitive decline in patients with mild cognitive impairment and Alzheimer's disease dementia. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100658
PREVALENCE OF DEMENTIA AND BPSD IN COMMUNITY-DWELLING OLDER ADULTS WITH ADVANCED CARE NEEDS: A NATIONWIDE SURVEY IN TAIWAN
Kai-Ming Jhang, Yu-Chun Tung, Wen-Fu Wang, Hsiang-Ju Chung, Hui-Yi Liao, Ling-Chun Huang, Chih-Cheng Hsu, Yuan-Han Yang
J Prev Alz Dis 2026;9(13)
Show summaryHide summaryBACKGROUND: Caring for people with both dementia and advanced care needs is complex. This study aimed to elucidate the prevalence of dementia and behavioral and psychological symptoms of dementia (BPSD) in patients receiving advanced care, including tube feeding, respiratory care, subcutaneous injection, urinary catheter, stoma care or enema, wound care, pain care, or dialysis.
METHODS: This study was a nationwide, population-based, cross-sectional survey. A total of 11,297 participants were enrolled between September 2020 and June 2022 using a multistage stratified systematic sampling design. Dementia diagnosis was made by subspecialists during in-home visit or by expert consensus. The presence of BPSD and the use of specific advanced care services were collected by trained interviewers.
RESULTS: Overall, 732 (6.5%) participants received at least one item of advanced care and 975 (8.6%) were diagnosed with dementia. Participants receiving advanced care had a higher prevalence of dementia (18.0%vs. 8.0%, p < 0.0001). Subjects receiving stoma or enema care (OR=4.92, 95% CI=2.29–10.59, p < 0.0001), tube feeding (OR=3.20, 95%CI=1.99–5.15, p < 0.0001), dialysis (OR=2.97, 95% CI=1.80–4.92, p < 0.0001), urinary catheterization or intermittent catheterization (OR=2.20, 95% CI=1.32–3.67, p = 0.003), and respiratory care (OR=2.01, 95% CI=1.14–3.57, p = 0.017) had a significantly higher risk of dementia. For BPSD, day–night confusion (42.0%vs. 27.9%, p = 0.002) and care-resistant behaviors (19.8%vs. 12.0%, p = 0.019) were significantly more prevalent in participants receiving advanced care.
CONCLUSIONS: This study found that patients receiving advanced care had a significantly higher prevalence of dementia and BPSD in Taiwanese population. Healthcare professionals should be vigilant regarding potential comorbid dementia in patients receiving advanced care and provide more patient-centered approaches or non-pharmacological interventions to alleviate BPSD and reduce care partner’s loading.
CITATION:
Kai-Ming Jhang ; Yu-Chun Tung ; Wen-Fu Wang ; Hsiang-Ju Chung ; Hui-Yi Liao ; Ling-Chun Huang ; Chih-Cheng Hsu ; Yuan-Han Yang (2026): Prevalence of dementia and BPSD in community-dwelling older adults with advanced care needs: a nationwide survey in Taiwan. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100656
NATIONAL PREVALENCE AND CARE NEEDS OF DEMENTIA IN ADULTS AGED >=55 YEARS: FINDINGS FROM THE CHINA MENTAL HEALTH SURVEY
Zhaorui Liu, Guangming Xu, Ruoxi Ding, Chao Ma, Yueqin Huang, Lingjiang Li, Tingting Zhang, Jie Yan, Yaqin Yu, Xiufeng Xu, Zhizhong Wang, Yifeng Xu, Tao Li, Huifang Yin, Xiangdong Xu, Limin Wang, Yongping Yan, Shuiyuan Xiao
J Prev Alz Dis 2026;9(13)
Show summaryHide summaryBACKGROUND: Dementia is a major global mortality cause and key driver of disability in older adults, imposing multidimensional burdens. As China's population ages, accurate prevalence estimates and care need assessments are essential for equitable policy planning. This study investigates young- and late-onset dementia prevalence while comparing health service utilization and unmet care needs between affected and unaffected populations.
METHODS: Utilizing China Mental Health Survey data (2013-2015) with multistage probability sampling, we identified 12,663 nationally representative adults aged ≥55 years. Of these, 10,839 completed Stage I assessments and 2,261 received Stage II evaluations, supplemented by psychiatric assessments of initial non-participants (n=197). Dementia diagnosis followed DSM-IV criteria via validated cognitive/functional instruments. Health service utilization and multidimensional care needs (ADLs/IADLs/safety) were quantified through participant/informant interviews.
RESULTS: Among 2 458 participants assessed, dementia prevalence was 2.65% (55-64y) and 5.56% (≥65y). Rural residents showed consistently higher rates than urban counterparts across age groups. Significant education gradients emerged, with urban prevalence decreasing with higher education while rural patterns differed. Individual living with dementia required substantially more care for both samples (55-64 years: 37.4% vs 11..9%, +81.3 monthly hours; 65+ years: 62.6% vs 13.4%, +88.8 monthly hours) without increased health service utilization.
CONCLUSION: This national study reveals substantial dementia burden in China, exposing systemic healthcare deficiencies through misaligned functional care needs and medical engagement. The neglect of chronic disability management in aging populations necessitates urgent integration of prevention strategies and tailored support frameworks within primary care systems.
CITATION:
Zhaorui Liu ; Guangming Xu ; Ruoxi Ding ; Chao Ma ; Yueqin Huang ; Lingjiang Li ; Tingting Zhang ; Jie Yan ; Yaqin Yu ; Xiufeng Xu ; Zhizhong Wang ; Yifeng Xu ; Tao Li ; Huifang Yin ; Xiangdong Xu ; Limin Wang ; Yongping Yan ; Shuiyuan Xiao (2026): National Prevalence and Care Needs of Dementia in Adults Aged >=55 Years: Findings from the China Mental Health Survey. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100659
LETTER TO THE EDITOR : FROM REGULATORY APPROVAL TO CLINICAL PRACTICE: REAL-WORLD ELIGIBILITY FOR ANTI-AMYLOID MONOCLONAL ANTIBODIES IN AN ITALIAN DEMENTIA-CARE NETWORK
Giovanna Zamboni, Manuela Tondelli, Giulia Vinceti, Chiara Gallingani, Zeno Bercini, Aurora Barbieri, Chiara Carbone, Najara Iacovino, Silvia Cossutti, Daniela Ballotta, Simone Salemme, Annalisa Chiari
J Prev Alz Dis 2026;9(13)
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CITATION:
Giovanna Zamboni ; Manuela Tondelli ; Giulia Vinceti ; Chiara Gallingani ; Zeno Bercini ; Aurora Barbieri ; Chiara Carbone ; Najara Iacovino ; Silvia Cossutti ; Daniela Ballotta ; Simone Salemme ; Annalisa Chiari (2026): Letter to the Editor: From regulatory approval to clinical practice: real-world eligibility for anti-amyloid monoclonal antibodies in an Italian dementia-care network. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100655
LETTER TO THE EDITOR : OXIDATION OVER OMEGA-3: REINTERPRETING THE PARADOXICAL LINK BETWEEN FISH OIL SUPPLEMENTS AND ACCELERATED COGNITIVE DECLINE
Dong\'e Huang, Munan Lin, Junqing Dong
J Prev Alz Dis 2026;9(13)
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CITATION:
Dong'e Huang ; Munan Lin ; Junqing Dong (2026): Letter to the Editor: Oxidation over omega-3: Reinterpreting the paradoxical link between fish oil supplements and accelerated cognitive decline. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100660
LETTER TO THE EDITOR : DO METHODOLOGICAL LIMITATIONS AND CONFOUNDING FACTORS EXPLAIN THE APPARENT ACCELERATION OF COGNITIVE DECLINE IN OLDER ADULTS TAKING OMEGA-3 FATTY ACID SUPPLEMENTS?
Simon C. Dyall, Mélanie Plourde
J Prev Alz Dis 2026;9(13)
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CITATION:
Simon C. Dyall ; Mélanie Plourde (2026): Letter to the Editor: Do methodological limitations and confounding factors explain the apparent acceleration of cognitive decline in older adults taking omega-3 fatty acid supplements?. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100661
LETTER TO THE EDITOR : RESPONSE TO TWO LETTERS ON OMEGA-3 SUPPLEMENTATION AND COGNITIVE DECLINE
Zheng-Bin Liao, Ye-Ran Wang
J Prev Alz Dis 2026;9(13)
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CITATION:
Zheng-Bin Liao ; Ye-Ran Wang: Letter to the Editor: Response to two letters on omega-3 supplementation and cognitive decline. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100662
CORRIGENDUM TO “REAL-WORLD LONG-TERM CONTINUATION OF LECANEMAB THERAPY AND THE CLINICAL UTILITY OF PHOSPHORYLATED TAU 181” [THE JOURNAL OF PREVENTION OF ALZHEIMER\'S DISEASE (2026) 100664]
Moeko Noguchi-Shinohara, Daiki Muramatsu, Ayano Shima, Yasuhiro Sakashita, Yasutake Tada, Hiroki Yamaguchi, Junji Komatsu, Tokuhei Ikeda, Kenjiro Ono
J Prev Alz Dis 2026;9(13)
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CITATION:
Moeko Noguchi-Shinohara ; Daiki Muramatsu ; Ayano Shima ; Yasuhiro Sakashita ; Yasutake Tada ; Hiroki Yamaguchi ; Junji Komatsu ; Tokuhei Ikeda ; Kenjiro Ono: Corrigendum to “Real-world long-term continuation of lecanemab therapy and the clinical utility of phosphorylated tau 181” [The Journal of Prevention of Alzheimer's Disease (2026) 100664]. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.1016/j.tjpad.2026.100668