J. Alzheimers Dis. [JOURNAL]
Sun
200 papers
Weight instability and risk of incident dementia among older stroke survivors: A nationwide cohort study.
Kim S, Cho B
J Alzheimers Dis · 2026 Apr · PMID 42024113 · Publisher ↗
BackgroundWeight loss, weight gain, and body mass index (BMI) instability have been linked to dementia risk in older adults. Stroke survivors may be particularly vulnerable to accelerated cognitive decline due to impaire...
BackgroundWeight loss, weight gain, and body mass index (BMI) instability have been linked to dementia risk in older adults. Stroke survivors may be particularly vulnerable to accelerated cognitive decline due to impaired physiological reserve and nutrition-related challenges. However, evidence on BMI change and dementia in this high-risk population remains limited.ObjectiveTo investigate the association between annual BMI change and incident dementia in a nationwide cohort of older stroke survivors.MethodsUsing KNHIS data, we identified adults aged ≥65 years with a history of stroke who underwent repeated health examinations. Annual BMI change was categorized as decreased (≤-1 kg/m/year), stable (-1 to <1), or increased (≥1). Incident dementia (2013-2022) was defined using ICD-10 diagnostic codes combined with anti-dementia medication prescriptions. Multivariable Cox proportional hazards models and stratified analyses were conducted.ResultsAmong 26,174 older stroke survivors, 6727 developed dementia over a mean follow-up of 5.40 ± 2.73 years. Compared with stable BMI, both BMI decrease (HR 1.19; 95% CI 1.13-1.26) and BMI increase (HR 1.13; 95% CI 1.06-1.20) were associated with elevated dementia risk. The association for BMI decrease was consistent across sex and baseline BMI strata, whereas the association for BMI increase was primarily observed in men and those with normal baseline BMI.ConclusionsBoth BMI decreases and increases were associated with elevated dementia risk, with BMI decline showing the most consistent associations across subgroups. These findings suggest that monitoring weight trajectories may help identify older stroke survivors at heightened dementia risk in routine clinical practice.
Unmet social needs of community-living older adults with dementia: A scoping review.
Tan S, Markaryan M, Ribeiro Ó … +2 more , Branco RM, Sousa L
J Alzheimers Dis · 2026 Jun · PMID 42024112 · Full text
Dementia-related cognitive decline and ageing-related challenges impact social participation and relationships. Limited knowledge of dementia among family, friends and the public hinder support for interactions with thos...
Dementia-related cognitive decline and ageing-related challenges impact social participation and relationships. Limited knowledge of dementia among family, friends and the public hinder support for interactions with those affected. Unmet social needs in community-living older adults with dementia remain underrecognized, despite their importance in healthy ageing and quality of life. This scoping review mapped existing evidence on unmet social needs of community-living older adults with dementia, including how these needs vary across dementia stages. We conducted a scoping review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) and Joanna Briggs Institute (JBI) guidelines. Four databases were searched (2000 -April 2025) in English, Portuguese and Mandarin, yielding 24 included articles. Seven themes of unmet social needs were identified: (i) participation in out-of-home activities, (ii) support for maintaining independence in daily life (iii) companionship, (iv) meaningful relationships, (v) respectful and dignified social interactions, (vi) emotional support, and (vii) social needs during the pandemic. Unmet social needs differed by dementia stage: in mild dementia, unmet social needs mostly relate to out-of-home activities, while in moderate and severe stages unmet social needs shifted towards daily activities, companionship and emotional support. Stigma emerged as a transversal influence shaping experiences of unmet social need across stages and contexts. Unmet social needs evolve across dementia stages and are influenced by relational, socio-cultural and structural factors. Future research should include more advanced stages, diverse populations, and strategies for addressing social needs from their own perspectives.
Defining neurocognitive constructs underlying visual attention in mild cognitive impairment and dementia using digital assessment technology.
Libon DJ, Bazzano LA, Woo JG … +5 more , Price CC, Anda-Duran I, Chapin B, Urbina EM, Baliga G
J Alzheimers Dis · 2026 Jun · PMID 42024109 · Full text
BackgroundProblems with visual attention can be an early indication for the emergence of dementia.ObjectiveThe current research assessed visual attention using three iPad administered, digital cancellation tests.MethodsL...
BackgroundProblems with visual attention can be an early indication for the emergence of dementia.ObjectiveThe current research assessed visual attention using three iPad administered, digital cancellation tests.MethodsLetter and Symbol Cancellation Tests asked participants to circle a specific letter or symbol. On the Mixed Cancellation Test, participants alternated circling a letter, then a symbol. Five outcome variables were tallied: correct hits; mean intra-response pause or " time; mean drawing or " time to circle correct hits; mean distance or search between correct targets; and commission errors. All but commission errors were expressed in four cumulative time epochs; 0-30 s, 0-60 s, 0-90 s, and 0-120 s. Using a protocol of paper/ pencil neuropsychological tests, Jak, Bondi criteria were used to classify 145 memory clinic patients into groups suggesting normal cognitive abilities (CL; n = 45); subtle or mild cognitive impairment (MCI; n = 62); and mild dementia (DEM; n = 38).ResultsFor correct hits and mean pause/ "think" time, the three groups were dissociated from each other at 60, 90, and 120 s. For mean drawing/'ink' time far fewer between-group differences were found. There was no difference across the three tests for mean search. On the Symbol and Mixed Cancellation Tests, MCI and DEM patients produced more commission errors than CL participants.ConclusionsFaster pause or ", perhaps reflecting better disengagement from circling target items, may underlie better cancellation test performance. When brought to scale, The Rowan Cancellation Tests could be an effective means to screen for MCI and emergent dementia.
Cognitive characterization of the behavioral variant of frontotemporal dementia using the Neuronorma battery.
López-Carbonero JI, Peña-de Diego L, Valles-Salgado M … +8 more , Delgado-Álvarez A, Delgado-Alonso C, Fernández-Romero L, Barroso Y, Gil-Moreno MJ, Sánchez-Benavides G, Peña-Casanova J, Matías-Guiu JA
J Alzheimers Dis · 2026 Jun · PMID 42024107 · Publisher ↗
BackgroundFrontotemporal dementia (FTD) is a neurodegenerative disorder characterized by progressive behavioral changes, executive dysfunction, and language impairment. The behavioral variant (bvFTD) is the most common f...
BackgroundFrontotemporal dementia (FTD) is a neurodegenerative disorder characterized by progressive behavioral changes, executive dysfunction, and language impairment. The behavioral variant (bvFTD) is the most common form and often overlaps clinically with psychiatric disorders and Alzheimer's disease (AD), complicating early diagnosis. Neuropsychological assessment is therefore essential, yet standardized tools for bvFTD are limited.ObjectiveThis study aimed to characterize the cognitive profiles of bvFTD across prodromal and demented stages using the Neuronorma neuropsychological battery.MethodsWe analyzed clinical and neuropsychological data from 122 bvFTD patients, including 35 prodromal (Clinical Dementia Rating (CDR) 0.5) and 87 demented (CDR>0.5) cases. Cognitive domains assessed were attention, executive function, memory, verbal fluency, naming, and visuospatial abilities, with impairment defined using two Z-score thresholds (≤ -1 and ≤ -1.67). Patient performance was compared to age-, sex-, and education-matched healthy controls.ResultsWe found frequent deficits in executive function, semantic fluency, verbal and visual memory, and visuospatial abilities, even among prodromal patients. Multi-domain impairment predominated in demented cases, whereas prodromal profiles were heterogeneous, occasionally presenting isolated memory deficits. Comparison with matched controls confirmed significant differences across most tests, with large effect sizes in memory, executive function, attention, and verbal fluency.ConclusionsThese findings support the use of the Neuronorma battery for the cognitive assessment of bvFTD, from the prodromal stages. Furthermore, the presence of non-executive cognitive deficits in bvFTD highlights the need for comprehensive cognitive profiling in differential diagnosis.
A diary-based approach to improve neuropsychiatric symptom assessment in dementia: A cross-sectional comparison with the neuropsychiatric inventory.
Toccaceli Blasi M, Salzillo M, Buscarnera S … +8 more , Nuti F, Stanziale C, Pecorari C, Ottone DA, Salati E, D'Antonio F, Canevelli M, Bruno G
J Alzheimers Dis · 2026 Jun · PMID 42024106 · Publisher ↗
BackgroundNeuropsychiatric symptoms (NPS) are among the most challenging manifestations of dementia. Currently available assessment tools often fail to fully capture their complexity. Thus, novel approaches are needed.Ob...
BackgroundNeuropsychiatric symptoms (NPS) are among the most challenging manifestations of dementia. Currently available assessment tools often fail to fully capture their complexity. Thus, novel approaches are needed.ObjectiveThe present study aimed to explore the application of a diary-based assessment of NPS in patients with dementia attending a memory clinic and compare this novel approach with the Neuropsychiatric Inventory (NPI) in terms of scores, time efficiency, and influence of potential confounders.MethodsAll consecutive outpatients with dementia and NPS attending the Center for Cognitive Disorders and Dementia, Sapienza University of Rome, were considered for enrollment. Caregivers completed a specially designed NPS diary for one month. Subsequently, a standard NPI (sNPI) was administered, and two diary-based NPIs (dNPI-R1 and dNPI-R2) were independently reconstructed by trained raters. Scores were compared using repeated-measures ANOVA and Cochran's Q test. Multivariate regression models were conducted to examine the impact of covariates. In addition, the NPS diary was qualitatively analyzed, and caregivers provided structured feedback.ResultsForty patient-caregiver dyads completed the study procedures. The sNPI yielded higher scores and longer administration time than dNPIs. Diary-based assessments showed high inter-rater reliability and were less influenced by caregiver burden.ConclusionsThe NPS diary offered an ecological, caregiver stress-resistant, reliable, time-efficient, and feasible evaluation of NPS. It allowed a detailed description of NPS, including temporal fluctuations, triggers, and resolution strategies. Integration of this complementary modality with standard evaluations allows a more comprehensive assessment of NPS in dementia.
Larger baseline body stature predicts one-year amyloid change in cognitively normal older adults enriched with elevated amyloid status.
Smith AN, Burns JM, Sullivan DK … +5 more , Morris JK, Carbuhn AF, Herda TJ, Thyfault JP, Taylor MK
J Alzheimers Dis · 2026 Jun · PMID 42024105 · Publisher ↗
BackgroundRising Alzheimer's disease (AD) incidence underscores the need to identify modifiable risk factors. The "obesity paradox" suggests higher late-life body mass index (BMI) may reduce AD risk. Because BMI does not...
BackgroundRising Alzheimer's disease (AD) incidence underscores the need to identify modifiable risk factors. The "obesity paradox" suggests higher late-life body mass index (BMI) may reduce AD risk. Because BMI does not distinguish between fat and lean mass, investigating body composition and brain amyloid accumulation may clarify this relationship.ObjectiveThis study tested whether baseline body stature predicts one-year change in brain amyloid.MethodsUsing data from the Alzheimer's Prevention through Exercise trial, we examined whether baseline body stature and composition (BMI, fat mass index [FMI], lean mass index [LMI], and total fat and lean mass) predicted one-year change in brain amyloid among 106 cognitively healthy older adults enriched with elevated amyloid status.ResultsHigher baseline BMI predicted less one-year amyloid accumulation globally (β = -0.33, p = 0.001) and in five of six brain regions (p = 0.001-0.05). Higher FMI predicted less amyloid accumulation globally (β = -0.35, p < 0.001) and in all six regions (p < 0.001-0.02), while higher LMI predicted less accumulation globally and in four regions (p < 0.001-0.02). Higher total fat mass was associated with less amyloid globally and regionally (p < 0.001-0.02), whereas higher total lean mass predicted reduced accumulation only in the lateral temporal lobe (p = 0.01).ConclusionsLarger body mass predicted less amyloid accumulation in cognitively healthy older adults over one year. More research is needed to investigate whether larger body stature protects against amyloid accumulation and explore underlying mechanisms.Clinical Trial RegistrationClinicalTrials.gov, Identifier (NCT02000583).
How amyloid-β peptide choice shapes neurochemical outcomes in intracerebral rat models of Alzheimer's disease: A systematic review.
Agavriloaei LM, Costachescu I, Szilagyi A … +3 more , Gogu MR, Iliescu BF, Turliuc MD
J Alzheimers Dis · 2026 Jun · PMID 42024102 · Publisher ↗
BackgroundIntracerebral administration of amyloid-β (Aβ) peptides remains a widely used experimental approach for modeling key neurochemical features of Alzheimer's disease (AD), including neuroinflammation, oxidative st...
BackgroundIntracerebral administration of amyloid-β (Aβ) peptides remains a widely used experimental approach for modeling key neurochemical features of Alzheimer's disease (AD), including neuroinflammation, oxidative stress, and synaptic dysfunction. Among these models, Aβ and Aβ are most frequently employed. However, their effects are often treated as interchangeable despite recognized differences in aggregation behavior and biological activity.ObjectiveThis systematic review aimed to synthesize evidence on how peptide selection between Aβ and Aβ shapes neurochemical outcomes in intracerebral rat models of AD.MethodsThe review was conducted in accordance with PRISMA guidelines and registered in PROSPERO. A structured search identified in vivo rat studies using Aβ or Aβ. Given methodological heterogeneity, findings were synthesized using a qualitative framework. To address potential structural confounding, stratified analyses were performed according to injection route and aggregation state.ResultsEighty-three studies met inclusion criteria (Aβ = 60; Aβ = 23). Across neurochemical domains, Aβ was more frequently associated with earlier and glial activation, increased pro-inflammatory mediators, oxidative imbalance, and synaptic alterations, often accompanied by behavioral deficits. In contrast, Aβ models showed a more variable and generally attenuated neurochemical response with greater dependence on experimental parameters. Structural analyses indicated clustering by injection route, whereas aggregation-state distribution was not statistically skewed between peptides.ConclusionsThe available evidence suggests that Aβ and Aβ should not be assumed interchangeable without explicit methodological consideration. Observed differences appear context-dependent and influenced by experimental design variables. Peptide selection with defined mechanistic objectives may enhance interpretability and translational relevance in preclinical AD research.
Whole genome sequencing analysis of over 3500 individuals dementia-free over 85 years old.
Peloso GM, Wang D, Abbruzzese SM … +23 more , Bis JC, Choi SH, Beiser A, Bressler J, Dupuis J, Fohner AE, Ghanbari M, Gibbs RA, Heard-Costa N, Ikram MA, Lacaze P, Le Grand Q, Lopez OL, Mosley TH, Riaz M, Soumaré A, Yaqub A, Boerwinkle E, Psaty BM, Fornage M, TOPMed Neurocognitive Working Group, The Alzheimer’s Disease Neuroimaging Initiative (ADNI), Alzheimer’s Disease Sequencing Project, Seshadri S, DeStefano AL
J Alzheimers Dis · 2026 Jun · PMID 42024100 · Full text
BackgroundIdentifying genetic variants conferring resilience to Alzheimer's disease and related dementia (ADRD) may hold promise for developing therapeutics.ObjectiveTo determine genetic associations with being dementia-...
BackgroundIdentifying genetic variants conferring resilience to Alzheimer's disease and related dementia (ADRD) may hold promise for developing therapeutics.ObjectiveTo determine genetic associations with being dementia-free at age 85 (DF85).MethodsWe examined genetic associations, using whole genome sequencing data, with DF85 in three Trans-Omics for Precision Medicine cohorts and the Alzheimer's Disease Sequencing Project Phenotype Harmonization Consortium. We tested common variants individually and aggregation of rare (MAF ≤ 1%) coding and non-coding variants in DF85 participants (n = 3657) against individuals who were not DF85 (n = 20,010). We verified associations using a stricter control set who developed dementia before age 85 (n = 5552).ResultsWe observed an association at (rs429358, MAF = 0.21, odds ratio [OR] = 0.49, 95% confidence interval [CI] = 0.46-0.53, p = 1.0 × 10) as well as for two common variants (rs16892237-A near , MAF = 0.08, OR = 1.34, 95% CI = 1.21-1.48, p = 1.1 × 10 and rs8004018-G near , MAF = 0.16, OR = 1.24, 95% CI = 1.15-1.34, p = 1.7 × 10) and an aggregate of rare loss of function and disruptive missense variants in on chr 17 (p = 1.4 × 10) associated with DF85.ConclusionsThrough a genome-wide assessment of a resilience-focused outcome, we identified common and rare genetic variants contributing to DF85 status. Genes associated with DF85 may delay onset of ADRD and provide translational impact.
Mapping hotspots of self-reported dementia and memory clinics across Australia.
Phan ALG, Beare R, Ma H … +2 more , Srikanth V, Phan TG
J Alzheimers Dis · 2026 Jun · PMID 42024099 · Publisher ↗
BackgroundDementia prevalence is increasing in Australia. It is unknown whether there are hotspots for dementia in metropolitan or non-metropolitan areas. This knowledge is important for healthcare planning.ObjectiveThis...
BackgroundDementia prevalence is increasing in Australia. It is unknown whether there are hotspots for dementia in metropolitan or non-metropolitan areas. This knowledge is important for healthcare planning.ObjectiveThis paper will examine where hotspots for self-reported dementia in Australia are, and whether they are adequately serviced by multidisciplinary memory clinics.MethodsWe used self-reported dementia data from the 2021 Australian Census at the local government area (LGA) level. LGAs represent public administrative regions within Australian states and territories. Standardized prevalence ratios (SPR) were calculated for each LGA by dividing the number of self-reported cases by the expected number of cases. Spatial relationships were investigated with Bayesian spatial regression using integrated nested Laplace approximations. Memory clinics were located using Australian Dementia Network and government websites.ResultsSelf-reported dementia prevalence was lower in metropolitan areas (72.3 per 10,000) compared to non-metropolitan areas (79.9 per 10,000). There are 108 multidisciplinary memory clinics in Australia, 83 of which are metropolitan. Hotspots for self-reported dementia occurred in non-metropolitan east coast of New South Wales (SPR: 2.13), southeast Queensland (SPR: 1.72), and northwest of greater city Adelaide (SPR: 2.55). LGAs in major cities had lower SPRs (Melbourne: 0.40; Sydney: 0.45), apart from Western Adelaide (SPR: 1.88).ConclusionsHotspots for self-reported dementia were mainly in non-metropolitan Australia, whereas memory clinic services were mostly in metropolitan areas, raising issues of equity and access to services.
Accelerated long-term forgetting in Alzheimer's disease continuum: A systematic review and meta-analysis.
Pizzoni L, Piero AD, Blasutto B … +3 more , Casagrande M, Piccardi L, Guariglia C
J Alzheimers Dis · 2026 Jun · PMID 42024098 · Publisher ↗
BackgroundAccelerated long-term forgetting (ALF), the disproportionate loss of information over days or weeks despite normal performance at standard delays, has been proposed as an early cognitive marker of Alzheimer's d...
BackgroundAccelerated long-term forgetting (ALF), the disproportionate loss of information over days or weeks despite normal performance at standard delays, has been proposed as an early cognitive marker of Alzheimer's disease (AD).ObjectiveProvide a qualitative and quantitative synthesis of current evidence on ALF across the AD continuum.MethodsWe performed a systematic review and meta-analysis following the PRISMA 2020 guidelines. Eligible studies evaluated episodic memory with delays of at least 1 h in participants across the AD continuum compared to healthy controls. Risk of bias was assessed using the Joanna Briggs Institute (JBI) tools, and pooled effect sizes (Hedges' g) were calculated for delays of 1 day, 1 week, and 1 month or longer.ResultsTwenty-eight studies (n = 1399) were included; 16 entered quantitative analyses. The 1-day effect was nonsignificant (g = 0.55, 95% CI -0.03-1.12). At 1 week, ALF effect was robust (g = 0.63, 95% CI 0.40-0.87; I = 0%) and evident in at-risk groups (g = 0.61, 95% CI 0.37-0.86) despite intact early retention. Both verbal (g = 0.74) and non-verbal (g = 0.53) tasks, as well as recall (g = 0.61) and recognition (g = 0.70), showed similar sensitivity. Effects persisted at ≥1 month but weakened in at-risk groups.ConclusionsALF is strongly detected in the preclinical stage of AD, especially at a 1-week delay across different materials and retrieval methods. Long-delay memory tests may enhance the sensitivity of neuropsychological assessments for detecting early cognitive issues in the early stages of the AD continuum.
Attitudes of older adults toward active euthanasia in advanced Alzheimer's disease.
Kermel-Schiffman I, Lifshitz R, Carmel S … +1 more , Bachner YG
J Alzheimers Dis · 2026 Jun · PMID 42024095 · Full text
BackgroundActive euthanasia by physicians involves administering a substance that directly causes a patient's death. In Alzheimer's disease, progressive cognitive decline and increasing dependence raise complex ethical a...
BackgroundActive euthanasia by physicians involves administering a substance that directly causes a patient's death. In Alzheimer's disease, progressive cognitive decline and increasing dependence raise complex ethical and emotional dilemmas. Although legalized in some countries, active euthanasia remains controversial, with public attitudes shaped by multiple factors, particularly in advanced disease stages.ObjectiveThis study examined older adults' attitudes toward active euthanasia in advanced Alzheimer's disease from three perspectives: toward themselves, a family member, and an unknown individual. It also explored associations between sociodemographic and psychosocial variables and these attitudes.MethodsA quantitative study was conducted with 501 individuals aged 75+, recruited through day centers and snowball sampling. Attitudes were measured using hypothetical cases involving euthanasia decisions for oneself, a family member, and an unknown individual. Variables included self-efficacy, will to live, desire to prolong life, life satisfaction, fear of death, social support, and sociodemographic characteristics. Analyses employed mean comparisons and hierarchical linear regression models.ResultsParticipants reported the most favorable attitudes toward euthanasia when considering themselves (M = 3.61), followed by a family member (M = 3.22), with the least favorable attitudes expressed toward an unknown individual (M = 2.86). Lower desire to prolong life and higher self-efficacy predicted more positive attitudes across all cases, while lower will to live was positively associated only in personal and familial contexts. Female gender, higher education, and lower religiosity were linked to more favorable attitudes across all contexts.ConclusionsSociodemographic and personality characteristics should be considered when developing strategies aimed at increasing public awareness of active euthanasia, especially among older adults.
Association of inflammation-related plasma proteins with vascular cognitive burden and Alzheimer's disease: A multi-method study.
Ye Z, Teng B, Wang S … +13 more , Zhu J, Chen J, Zhang B, Cai H, Wei R, Li B, Xie X, Yu X, Li J, Huang S, Weng Y, Yang D, Alzheimer's Disease Neuroimaging Initiative
J Alzheimers Dis · 2026 Jun · PMID 42024094 · Publisher ↗
BackgroundInflammation is implicated in the pathogenesis of dementia. However, its role in the vascular cognitive burden and the clinical stage of Alzheimer's disease (AD) remains controversial.ObjectiveThis study aimed...
BackgroundInflammation is implicated in the pathogenesis of dementia. However, its role in the vascular cognitive burden and the clinical stage of Alzheimer's disease (AD) remains controversial.ObjectiveThis study aimed to explore the association of plasma inflammatory proteins with vascular cognitive burden and clinical stage of AD by using a multi-method approach.MethodsWe included 330 individuals with complete plasma protein profiles, Hachinski Ischemia Scale scores, and cognitive function status between September 13, 2005, and October 24, 2007. We employed generalized linear models, restricted cubic splines, and the inverse variance weighting (IVW) method for two-sample Mendelian randomization (MR) to investigate the correlation between inflammatory biomarkers and dementia. We employed the random forest algorithm to build predictive models and utilized SHapley Additive exPlanations (SHAP) analysis for feature importance and interpretability.ResultsAD clinical stage exhibited significant associations with cortisol, C-peptide, tumor necrosis factor receptor-2 (TNFR-2) and interleukin-16 (IL-16, all < 0.05). Similarly, the vascular cognitive burden was significantly correlated with C-peptide, carcinoembryonic antigen and TNFR-2 (all < 0.05). These observational findings were corroborated by SHAP analysis. Subsequent MR analysis further revealed a weak negative causal relationship between AD and IL-16 ( = 0.003; OR = 0.981; 95% CI: 0.969-0.994).ConclusionsOur study identified several inflammatory proteins correlated with the vascular cognitive burden and AD clinical stage, providing exploratory evidence for future mechanistic and interventional research.
Effect of sex on trajectories of verbal learning and memory and clinical symptoms in diverse Alzheimer's disease cohorts.
Levine TF, Mashinchi GM, Rodrigues J … +3 more , Cross CL, Caldwell JZK, Health and Aging Brain Study (HABS-HD) Study Team *
J Alzheimers Dis · 2026 Jun · PMID 42024093 · Publisher ↗
BackgroundWomen continue to demonstrate a verbal learning and memory advantage compared to men even in the earliest stages of Alzheimer's disease (AD). However, the literature on sex differences in longitudinal AD trajec...
BackgroundWomen continue to demonstrate a verbal learning and memory advantage compared to men even in the earliest stages of Alzheimer's disease (AD). However, the literature on sex differences in longitudinal AD trajectories is sparse, particularly in ethnically diverse samples.ObjectiveTo examine sex differences in verbal learning and memory, as well as clinical symptoms, in clinically normal non-Hispanic white (NHW) and Hispanic/Latino (HL) cohorts longitudinally.MethodsWe examined longitudinal sex effects on verbal learning and memory (Spanish-English Verbal Learning Test) and clinical symptoms (Clinical Dementia Rating Scale-Sum of Boxes) in NHW (n = 529) and HL (n = 439) participants with available AD biomarkers (plasma Aβ/Aβ and hippocampal volume) who were clinically normal at baseline and completed follow-up assessment 18-24 months later.ResultsIn both cohorts, women demonstrated higher verbal learning and memory scores at baseline (ps < 0.001). In the NHW cohort, longitudinal sex differences were observed in verbal learning and memory, with women maintaining performance over time, whereas men's performance declined (p = 0.071 and p = 0.020, respectively). In the HL cohort, longitudinal sex differences were observed in clinical symptoms, with men demonstrating greater decline than women (p = 0.033). Trajectories of decline did not significantly differ between ethnic cohorts. AD biomarkers did not moderate observed effects.ConclusionsThis study highlights the potential impact of ethnicity on sex-based differences in cognitive decline in older adulthood. Future work is needed to determine best practices for tracking progression along the AD continuum, particularly within the preclinical phase.
Beliefs, barriers, and behaviors: Exploring dementia prevention perspectives in culturally diverse populations in The Netherlands.
Lazaar N, Rirash AF, Papma JM … +2 more , Mattace Raso FUS, Franzen S
J Alzheimers Dis · 2026 Jun · PMID 42024089 · Full text
BackgroundModifiable risk factors play a key role in preventing or delaying dementia, yet little is known about how culturally diverse populations in Europe perceive these risk factors.ObjectiveThis study aimed to: (1) e...
BackgroundModifiable risk factors play a key role in preventing or delaying dementia, yet little is known about how culturally diverse populations in Europe perceive these risk factors.ObjectiveThis study aimed to: (1) explore lay perceptions of dementia and its risk factors, and (2) examine how these perceptions interact with social and structural determinants of health to shape dementia prevention behaviors.MethodsWe conducted a qualitative study guided by the I-Change model, using semi-structured interviews with 20 adults varying in cultural and linguistic background, education, and age. Interviews were conducted in Dutch, English, and Moroccan-Arabic (), translated if needed and transcribed verbatim. Data analysis followed open, axial, and selective coding to identify themes.ResultsParticipants emphasized genetics and biological vulnerability over modifiable risk factors when discussing dementia risk. Socioeconomic status, physical ability, and (social) environment were perceived to shape opportunities for healthy aging. Peers, family, and cultural norms were both facilitators and barriers to health-promoting behaviors. Lived- and observed experiences of illness motivated general behavior change, not specifically linked to dementia and Alzheimer's disease. Stress, sleep, resilience, and discipline were viewed as influential for cognitive health. Participants often integrated personal, cultural, and social perspectives when interpreting dementia risk.ConclusionsPerceptions of dementia and Alzheimer's disease risk among culturally diverse individuals are shaped by biological beliefs, psychosocial influences, and social context. Knowledge of dementia and modifiable risk factors remains limited among minoritized populations. Public health initiatives might benefit from incorporating prevention messages in a community perspective to enhance engagement and motivation.
D-methionine improves spatial navigation and attenuates oxidative stress and amyloid pathology in a sex-specific manner.
Peck MR, Chapman JE, Hill T … +6 more , Quinn K, Ikiz ED, Lopez A, Hascup ER, Bae C, Hascup KN
J Alzheimers Dis · 2026 Jun · PMID 42024087 · Publisher ↗
BackgroundOxidative stress and maladaptive neuroimmune activation contribute to cognitive decline in Alzheimer's disease (AD) and represent therapeutic targets beyond amyloid-centered approaches.ObjectiveTo determine whe...
BackgroundOxidative stress and maladaptive neuroimmune activation contribute to cognitive decline in Alzheimer's disease (AD) and represent therapeutic targets beyond amyloid-centered approaches.ObjectiveTo determine whether oral D-methionine (D-Met), a redox-active amino acid, reduces amyloid pathology and lipid peroxidation and confers disease-modifying benefits in AD models.MethodsMale and female APP/PS1 and APP mice with advanced AD pathology received oral D-Met or vehicle. Behavioral assessments included locomotor activity and hippocampal-dependent spatial learning and memory. Amyloid burden, lipid peroxidation, peripheral metabolic, and inflammatory markers, and hippocampal microglial phenotypes were evaluated.ResultsD-Met did not alter locomotor or exploratory behavior but improved spatial memory recall in both sexes of APP/PS1 mice and in female APP mice. APP males exhibited improved Morris water maze learning. Amyloid pathology was region-specifically reduced, including decreased hippocampal plaque size in male APP mice, reduced cortical plaque size in female APP/PS1 mice, and lower soluble amyloid-β (Aβ) in male APP/PS1 mice. Lipid peroxidation was reduced only in female APP mice. D-Met induced pronounced sex-dependent peripheral effects, increasing adiposity and pro-inflammatory adipose signaling in males, while reducing perigonadal white adipose tissue IL-6 expression in female APP mice. In the hippocampus, D-Met decreased microglial activation, with female APP mice showing reduced Iba1 and disease-associated microglial markers and increased Axl expression.ConclusionsShort-term D-Met acts as a metabolic and redox modulator with amyloid-lowering effects mediated by improved microglial function. Therapeutic efficacy is strongly sex- and model-dependent, with the greatest benefit observed in female APP mice.
Transcriptome-based identification and experimental validation of a key gene in Alzheimer's disease using dermal fibroblasts.
Xie M, Niu X, Sun F … +1 more , Shi L
J Alzheimers Dis · 2026 Jun · PMID 42024084 · Publisher ↗
BackgroundAlzheimer's disease (AD) is a neurodegenerative disorder primarily characterized by progressive cognitive impairment and neuronal damage. The pathogenesis of AD is complex and involves multiple pathological pro...
BackgroundAlzheimer's disease (AD) is a neurodegenerative disorder primarily characterized by progressive cognitive impairment and neuronal damage. The pathogenesis of AD is complex and involves multiple pathological processes. Currently, effective methods for early diagnosis and treatment are lacking.ObjectiveTo identify key pathogenic genes and investigate their roles in Alzheimer's disease, we analyzed transcriptomic data from dermal fibroblasts of AD patients, aiming to assess their potential as novel biomarkers and therapeutic targets.MethodsTranscriptomic data from AD patient and control-derived dermal fibroblasts (DFs) were analyzed to identify differentially expressed genes. Key genes were screened using bioinformatics and a random forest algorithm. ceRNA analysis was performed to explore miRNA-mRNA interactions. The candidate gene SRSF5 was validated via overexpression and knockdown, followed by qPCR, western blotting, and reactive oxygen species (ROS) assays. The role of SRSF5 in endoplasmic reticulum (ER) stress was evaluated by measuring ER stress markers and cellular stress responses.ResultsTranscriptomic analysis revealed significant upregulation of SRSF5 in AD DFs. ceRNA analysis identified miRNAs regulating SRSF5 in AD. Overexpression of SRSF5 led to reduced neuronal proliferation, increased apoptosis, elevated ROS levels, and activation of ER stress markers (CHOP, GRP78, XBP1). SRSF5 knockdown alleviated these effects.ConclusionsSRSF5 may drive AD pathogenesis via ER and oxidative stress, serving as a potential biomarker and therapeutic target for early diagnosis and intervention.
Leveraging routine clinical data for dementia risk prediction using machine learning.
Ye Z, Zai A, Wang B … +6 more , Bennett A, Guilarte-Walker YG, Wong K, Zai AH, Erban S, Lin H
J Alzheimers Dis · 2026 Jun · PMID 42024083 · Publisher ↗
BackgroundEarly diagnosis of dementia is essential for enabling timely interventions that may slow disease progression, improve patient outcomes, and reduce healthcare costs. This study aims to develop machine learning m...
BackgroundEarly diagnosis of dementia is essential for enabling timely interventions that may slow disease progression, improve patient outcomes, and reduce healthcare costs. This study aims to develop machine learning models to predict dementia risk using longitudinal electronic health record (EHR) data.ObjectiveThis research aims to develop and evaluate machine learning models for dementia risk prediction using longitudinal EHR data from routine clinical care and to identify key clinical features associated with elevated dementia risks.MethodsWe conducted an incidence-based case-control study using EHR data from the UMass Memorial Health system (2017-2024) to develop a dementia risk prediction model.ResultsThis study included 5622 dementia cases and 44,976 controls. The XGBoost model achieved the highest AUC (0.802), with top predictors included thyroid-stimulating hormone (TSH), vitamin B12, and HDL cholesterol. Model performance was consistent across sexes and remained robust in multiple sensitivity analyses.ConclusionsMachine learning models that integrate comorbid conditions and longitudinal laboratory test patterns show their potential in predicting dementia risk. These findings highlight the promise of routinely collected EHR data as a scalable, low-cost resource for identifying individuals at elevated risk for dementia.
The association between hemoglobin level and risk of developing dementia.
Song JH, Kim HJ, Son M … +3 more , Kim HR, Kim SH, Kim HS
J Alzheimers Dis · 2026 Jun · PMID 42024081 · Publisher ↗
BackgroundHemoglobin levels are key indicators of health and may be associated with dementia risk. This study examined this association in a Korean population, stratified by sex.ObjectiveThis study aimed to evaluate the...
BackgroundHemoglobin levels are key indicators of health and may be associated with dementia risk. This study examined this association in a Korean population, stratified by sex.ObjectiveThis study aimed to evaluate the association between hemoglobin levels and the incidence of all-cause and subtype-specific dementia in a nationwide Korean cohort and to determine whether these associations differed by sex.MethodsFrom the National Health Insurance Service-National Health Screening Cohort, 316,542 adults aged ≥40 years were followed from 2004-2005 until 2019. Hemoglobin levels were divided into sex-specific quintiles. Dementia was defined by International Classification of Diseases, 10th Revision codes and prescriptions for anti-dementia medications. Risks of all-cause, Alzheimer's, and vascular dementia were analyzed using Cox proportional hazards models.ResultsCompared to the reference group (4th quintile), both the lower and higher hemoglobin quintiles were associated with an increased all-cause dementia risk (adjusted HR 1.16 [95% CI, 1.11-1.22] for Q1 and 1.07 [95% CI, 1.02-1.13] for Q5). Alzheimer's risk rose only in the lower quintiles, while vascular dementia risk rose at both extremes. These associations were stronger in women.ConclusionsAbnormal hemoglobin levels, particularly in women, were linked to an increased risk of dementia. Managing hemoglobin levels and correcting anemia may help prevent dementia.
Amyloid plaques associated with shift in patterns of hippocampal tau pathology in middle age.
Rodriguez-Reyes RF, Guo H, Luongo M … +4 more , Gomez-Isaza L, Pletnikova O, Troncoso JC, Morris M
J Alzheimers Dis · 2026 Jun · PMID 42024046 · Full text
BackgroundTau pathology begins to accumulate in the medial temporal lobe in many individuals in middle age. Some individuals develop amyloid pathology, more advanced tau pathology (Braak stage), and higher levels of CA1...
BackgroundTau pathology begins to accumulate in the medial temporal lobe in many individuals in middle age. Some individuals develop amyloid pathology, more advanced tau pathology (Braak stage), and higher levels of CA1 hippocampal tau pathology in the context of Alzheimer's disease. Others never develop significant amyloid pathology; in these cases, hippocampal tau pathology can be CA2-predominant and tends not to accumulate past intermediate stages. But factors associated with the early formation of these tau patterns is unclear.ObjectiveThe objective of this study is to examine demographic, genetic (), and pathologic factors associated with the emergence of hippocampal tau pathology patterns in middle age.MethodsWe identified 89 individuals with hippocampal tau pathology ages 65 and younger. These cases were assessed for tau stage, amyloid plaques, and status. Hippocampal tau pathology in CA1 and CA2 was scored semi-quantitatively.ResultsIn a younger aging population, tau pathology initially deposits at low levels in CA1 and CA2. In the presence of amyloid, tau pathology is increased in both CA1 and CA2, but with a shift toward a greater proportion of cases with higher tau pathology in CA1.ConclusionsPatterns of tau pathology in middle age are strongly associated with amyloid plaques, including increased CA1 and CA2 pathology and a greater proportion of CA1-predominant cases. In the absence of amyloid, tau pathology shows a normal (Gaussian) distribution between CA1 and CA2. These tau pathology distributions at younger ages are similar to the patterns seen at older ages in AD and PART.
Evaluating self- and informant-reported complaints as predictors of cognitive progression in subjective cognitive decline: A clinically-based evaluation.
Horakova H, Jester DJ, Vohradkova T … +10 more , Sheardova K, Ondrej J, Matuskova V, Fendrych Mazancova A, Nikolai T, Andel R, Lerch O, Laczó J, Hort J, Vyhnalek M
J Alzheimers Dis · 2026 Jun · PMID 42024038 · Publisher ↗
BackgroundSubjective cognitive complaints (SCCs) in cognitively normal older adults are associated with increased dementia risk. However, it remains uncertain which complaints best predict cognitive decline and whether p...
BackgroundSubjective cognitive complaints (SCCs) in cognitively normal older adults are associated with increased dementia risk. However, it remains uncertain which complaints best predict cognitive decline and whether predictive value differs between patient and informant reports.ObjectiveTo examine associations between self- and informant-reported total scores and individual items from the Questionnaire of Cognitive Complaints (QPC) and longitudinal cognitive decline in individuals with subjective cognitive decline (SCD).Methods261 individuals with SCD from the prospective Czech Brain Aging Study were followed longitudinally (mean 4.2-year follow-up). Linear mixed-effects models (random intercepts), adjusted for age, sex, and education, were estimated separately for self- and informant-reported QPC-total scores and for individual QPC-items to examine associations with change over time in global cognition, memory, and executive function/processing speed cognitive composites.ResultsHigher QPC-total scores predicted steeper decline across all cognitive composites in both self- and informant-reports, with modest effects. At the item level, after Bonferroni correction, informant-reported and were associated with a more pronounced decline across all cognitive composites exceeding the predictive value of the QPC-total score. Several other memory- and non-memory-related complaints showed associations in the same direction but did not consistently remain significant after correction.ConclusionsIn older adults with SCD, focusing on specific SCCs, particularly informant-reported memory complaints, rather than relying solely on global SCC score, allows more targeted identification of individuals whose complaints are most consistently associated with longitudinal cognitive decline. Structured assessments integrating informant perspective may improve early risk stratification.
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