Journal of Alzheimer's Disease最新文献

{"title":"Comparing operational definitions of screening-based cognitive impairment in the Tohoku Medical Megabank cohort: Focus on digital engagement.","authors":"Ryo Takano, John A Moyer, Takashi Fukushima, Jennings Xu, Kinya Okada","doi":"10.1177/13872877261498425","DOIUrl":"https://doi.org/10.1177/13872877261498425","url":null,"abstract":"<p><p>BackgroundDementia prevention is a global health priority, yet most large-scale population studies come from Western settings. Japan, a rapidly aging society, provides a unique non-Western epidemiological context for characterizing cognitive decline.ObjectiveTo assess whether the Tohoku Medical Megabank (TMM) cohorts replicate established dementia-related associations, and to identify correlates that are statistically significant across three prespecified operational classifications.MethodsWe analyzed data from >81,000 participants in the TMM cohorts. Participants were classified using (i) self-reported physician-diagnosed dementia and screening-defined impairment using (ii) Mini-Mental State Examination (MMSE) ≤ 27 and (iii) Japanese version of the Montreal Cognitive Assessment (MoCA-J) ≤ 25. Associations with 14 established dementia-related correlates and >3,800 exploratory variables were assessed using false-discovery-rate control, semantic clustering, and sequential multivariable logistic regression.ResultsParticipants with self-reported dementia had lower MMSE and MoCA-J scores. Established correlates replicated in expected directions for at least one classification, including lower education, hypertension, depressive symptoms, and hearing difficulty. We identified 106 significant correlates across all three classifications; for self-reported dementia, digital device non-use was associated with higher odds (fully adjusted OR up to 2.97, 95% CI: 1.42-6.18), while smartphone use showed inverse associations (OR = 0.47, 95% CI: 0.26-0.86); directions were consistent for screening-defined impairment.ConclusionsIn this study, leveraging existing cognitive classifications available in TMM cohorts, we found that established dementia-related associations largely replicated and identified correlates across three operational classifications. Digital disengagement emerged as a correlate that may reflect early functional change; given the cross-sectional design, causal inference requires further examination. Longitudinal validation with adjudicated diagnoses is needed.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261498425"},"PeriodicalIF":3.4,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evening chronotype and incidence of all-cause dementia and subtypes after accounting for other sleep traits: A prospective cohort study.","authors":"Jiaying Li, Jean Woo, Yijian Yang, Zengjie Ye, Junxin Li","doi":"10.1177/13872877261498357","DOIUrl":"https://doi.org/10.1177/13872877261498357","url":null,"abstract":"<p><p>BackgroundChronotype may affect neurophysiology, but whether its association with dementia persists independent of other sleep traits remains uncertain.ObjectiveTo examine associations of chronotype with incident dementia subtypes and potential modification by metabolic and social factors.MethodsIn 443,906 dementia-free participants, Cox models estimated dementia risk after adjustment for sociodemographic, lifestyle, clinical, apolipoprotein E (<i>APOE</i>) genotype, and sleep-related factors. We tested baseline interactions and robustness using multiple imputation, competing-risk models, and landmark analyses.ResultsOver a mean follow-up of 12.5 years, 6355 incident dementia cases were documented. Evening chronotype was associated with a small increased risk of all-cause dementia compared with morning types (HR, 1.07; 95% CI, 1.01-1.14). This association was observed primarily in \"other dementias\" (HR, 1.12; 1.04-1.21), with no significant association with Alzheimer's disease or vascular dementia (VaD).Exploratory subgroup analyses identified two interactions that remained significant after false discovery rate (FDR) correction: social visit frequency for all-cause dementia and napping for VaD (FDR-adjusted p for interaction is 0.024 for both). Evening chronotype was associated with higher all-cause dementia risk among participants reporting infrequent social visits and with higher VaD risk among those reporting usual napping.ConclusionsEvening chronotype was associated with a small increase in the hazard of all-cause dementia after multivariable adjustment. Given the modest magnitude and observational design, evening chronotype may be considered a potential risk marker rather than an independent or causal risk factor. These findings require independent replication.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261498357"},"PeriodicalIF":3.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"List of Reviewers.","authors":"","doi":"10.1177/13872877261499787","DOIUrl":"https://doi.org/10.1177/13872877261499787","url":null,"abstract":"","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261499787"},"PeriodicalIF":3.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between handedness and Alzheimer's disease: Results from a large MindCrowd observational study.","authors":"Charles Chen, Matt Huentelman, Kewei Chen","doi":"10.1177/13872877261498845","DOIUrl":"https://doi.org/10.1177/13872877261498845","url":null,"abstract":"<p><p>BackgroundHandedness is tied to the lateralization of brain functions and significantly affects cognitive function and brain activity. Alzheimer's disease (AD) is a progressive brain disorder that leads to declines in memory, thinking skills, and to behavioral changes, which also exhibits lateralized patterns of brain involvement. Understanding the relationship between handedness and AD may provide useful context for interpreting findings in AD research.ObjectivePrevious findings on the relationship between AD and handedness are inconsistent.We used the large MindCrowd dataset, comprising with over 150,000 participants, study the association between AD and handedness.MethodsWe applied logistic regression models to the data with and without adjustment for other covariates to estimate the association between handedness and AD. We also performed similar analyses for samples stratified by ages. We estimated the unadjusted and adjusted odds ratios (ORs) of having AD among left- and mixed-handed participants compared with right- handed participants.ResultsOur results showed that compared with right-handed participants, left- and mixed-handed participants had higher odds of self-reported AD (the overall adjusted OR: 2.08, 95% CI: (1.69, 2.53), p < 0.001)) being larger than that for left-handers (the overall adjusted OR: 1.42, 95% CI: (1.23, 1.64), p < 0.001)). Furthermore, for each age group considered, the estimated adjusted and unadjusted ORs for mixed-handers were consistently greater than that for left-handers; all were greater than 1.0.ConclusionsOur study confirmed that there is a significant association between handedness and AD. Our findings also indicate that mixed-handedness has a stronger association with AD than left-handedness.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261498845"},"PeriodicalIF":3.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149194182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The critical role of PET-based assessment of cerebrovascular disease in the management of patients with cognitive impairment and dementias.","authors":"Abass Alavi, Poul Flemming Høilund-Carlsen","doi":"10.1177/13872877261497232","DOIUrl":"https://doi.org/10.1177/13872877261497232","url":null,"abstract":"<p><p>A recent survey provides valuable insights into French practitioners' preparedness for implementing anti-amyloid immunotherapy (AAI) for Alzheimer's disease. It highlights the need for education but also underscores a broader challenge: clinicians must understand not only treatment protocols but also unresolved issues regarding diagnostic specificity, efficacy, safety, and cost-effectiveness. Amyloid biomarkers should not be considered definitive indicators of disease causality or treatment response. Greater attention should also be given to functional imaging approaches and cerebrovascular pathology, which may contribute to a more comprehensive understanding of cognitive decline. A balanced, evidence-based approach is essential before widespread adoption of AAI.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261497232"},"PeriodicalIF":3.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concurrent diagnostic efficiency and 8-year measurement stability of the weighted subjective memory complaints questionnaire-revised.","authors":"Yu Jung Choi, Ji Won Han, Ki Woong Kim","doi":"10.1177/13872877261498376","DOIUrl":"https://doi.org/10.1177/13872877261498376","url":null,"abstract":"<p><p>BackgroundSubjective memory complaints (SMC) are a potential early indicator of dementia, but whether their measurement properties hold over years of repeated assessment is unexamined. The weighted Subjective Memory Complaints Questionnaire-Revised (SMCQ-R) showed higher cross-sectional accuracy than the original SMCQ, but its performance over extended follow-up requires verification.ObjectiveTo evaluate whether SMCQ-R maintains measurement fidelity over 8 years relative to SMCQ and Mini-Mental State Examination (MMSE).MethodsWe analyzed 2057 community-dwelling older adults without baseline major depressive disorder from the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD), followed biennially for 8 years (5 assessments). Concurrent discriminative performance was evaluated via AUC, Cohen's d, signal-to-noise ratio (SNR). Sensitivity analysis excluded participants with incident depression during follow-up, and separately used all available data.ResultsAll three measures demonstrated excellent cross-sectional validity (mean AUC: SMCQ-R = 0.883, SMCQ = 0.889, MMSE = 0.884). SMCQ-R showed numerically larger effect sizes than SMCQ (Cohen's |d|: 1.884 versus 1.742, p = 0.154) and higher SNR (1.659 versus 1.485, p = 0.327), neither significant. Both subjective measures showed significant SNR reductions with incident depression, whereas MMSE remained robust.ConclusionsSMCQ-R showed a significant AUC decline over 8 years (slope = -0.0079/year, p = 0.024), but maintained clinically adequate accuracy (AUC ≥ 0.844), similar to SMCQ (0.883 vresus 0.889), despite a 36% reduction in item burden. Using all available data, this decline was not an artifact of the complete case restriction, and the MMSE discriminated at least as well as SMCQ-R at every assessment. SMCQ-R is regarded as an efficient complement to the MMSE rather than evidence of its superiority.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261498376"},"PeriodicalIF":3.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149194169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Locus coeruleus degeneration impairs forebrain arteriole physiology and perfusion in a rat model of Alzheimer's disease.","authors":"Mahsa Gifani, Laura C Chambers, Zachary Fernandez, John S Beck, Robert W Wiseman, Chunqi Qian, Anne M Dorrance, Scott E Counts","doi":"10.1177/13872877261496548","DOIUrl":"https://doi.org/10.1177/13872877261496548","url":null,"abstract":"<p><p>The locus coeruleus (LC) provides forebrain norepinephrine (NE) and degenerates early in Alzheimer's disease (AD). We have shown that experimental LC lesions in the Tg344-19 AD rat model result in parenchymal arteriole (PA) stenosis, blood-brain barrier permeability, amyloid angiopathy, and cognitive impairment. Here, we show that PAs from LC-lesioned Tg344-19 AD rats displayed increased myogenic tone and decreased responsiveness to TRPV4 channel agonists, which was reversible by NE replacement. MRI studies indicated reduced forebrain perfusion and fractional anisotropy in LC-lesioned animals compared to controls. Targeting LC-mediated effects on cerebral hemodynamics presents a compelling AD therapeutic target.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261496548"},"PeriodicalIF":3.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lower cardiac output is associated with longitudinal decreases in cerebrospinal fluid amyloid-β42, a core Alzheimer's disease biomarker, in women but not men.","authors":"Amalia J Peterson, Yunyi Sun, Dandan Liu, Kimberly R Pechman, Francis E Cambronero, Elizabeth E Moore, Deepak K Gupta, Timothy J Hohman, Henrik Zetterberg, Angela L Jefferson","doi":"10.1177/13872877261497236","DOIUrl":"https://doi.org/10.1177/13872877261497236","url":null,"abstract":"<p><p>Subclinical reductions in cardiac output relate to cognitive decline. We examined the relationship between cardiac output and cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease pathologies in 153 participants from the Vanderbilt Memory and Aging Project. Linear regression and linear mixed effects regression models related baseline cardiac output, assessed using echocardiogram, to CSF amyloid-β₄₂ (Aβ₄₂), Aβ₄₂/Aβ₄₀, and phosphorylated tau-181 cross-sectionally and longitudinally. Cardiac output interacted with sex on Aβ₄₂ levels longitudinally. Lower cardiac output was associated with lower Aβ₄₂ over time in women but not men. This may reflect cerebral Aβ accumulation or a more general change in Aβ production.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261497236"},"PeriodicalIF":3.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Terminal agitation in dementia: Challenges and opportunities.","authors":"Mustafa Atee, Rebecca Lloyd, Thomas Morris, Stephen Macfarlane","doi":"10.1177/13872877261496316","DOIUrl":"https://doi.org/10.1177/13872877261496316","url":null,"abstract":"<p><p>Terminal agitation (TA), also referred to as terminal restlessness or terminal delirium, is a complex, multifactorial clinical syndrome that occurs at the end of life. While TA is evident in dementia (including Alzheimer's disease), it is not exclusive to the condition and also occurs in other terminal illnesses, e.g., cancer. Currently, no clinical tools exist or have been validated to assess TA in dementia. This may hinder the correct identification of TA and further contribute to the incorrect estimation of TA prevalence. Due to the complex diagnostic profile of TA, it may be frequently underrecognized in individuals with dementia. There is also a lack of consensus on clinical terminology, operational definition (e.g., temporality, symptomology) and conceptualization of TA. This may be attributed in part to cultural context and the variability in describing the final stages of dementia. Thus, reported prevalence rates of TA in dementia are heterogeneous in the literature. Further, using multiple descriptions or terms for TA in the literature suggests that the syndrome may occur in groups, or clusters of symptoms. There is an association between pain, agitation, and delirium in various stages of dementia, particularly at the end of life. Differentiating TA, or delirium from behavioral and psychological symptoms of dementia (BPSD) is often difficult. The complex interaction between TA, dementia, and overlapping BPSD remains poorly understood and underresearched. Therefore, we outline priorities for future action and research, including the development of diagnostic and assessment tools to identify TA in dementia, and the establishment of consistent criteria for defining this syndrome.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261496316"},"PeriodicalIF":3.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic accuracy of plasma amyloid-β42 and Montreal Cognitive Assessment score as composite index for Alzheimer's disease in resource-limited settings: An exploratory study.","authors":"Amelia Nur Vidyanti, Pukovisa Prawiroharjo, Yuliarni Syafrita, Astuti Prodjohardjono, Atika Rahmadini, Putri Istiqomah Rizki Hidayatun, Rifki Habibi Rahman, Elizabeth Divina, Rani Permata, Alya Ayu Tazkia, Nailatul Fadhilah, Nanda Saripa Putri","doi":"10.1177/13872877261497299","DOIUrl":"https://doi.org/10.1177/13872877261497299","url":null,"abstract":"<p><p>BackgroundAccurate diagnosis of Alzheimer's disease (AD) in Indonesia remains challenging due to limited access to cerebrospinal fluid (CSF) analysis and PET imaging. Plasma amyloid-β42 (Aβ₄₂) may offer a less-invasive and affordable alternative, particularly when combined with cognitive assessment. However, its diagnostic performance in Indonesian populations is not well established.ObjectiveTo exploratorily assess the diagnostic accuracy of plasma Aβ₄₂, alone and as a composite index combined with Montreal Cognitive Assessment-Indonesian version (MoCA-INA) scores, as potential alternatives to CSF biomarkers for AD diagnosis in a resource-limited setting.MethodsA cross-sectional study was conducted involving 25 AD patients and 20 cognitively normal controls. Plasma and CSF biomarker levels were measured using ultrasensitive immunoassay. Cognitive function was evaluated using MoCA-INA. Receiver operating characteristic curve analysis was used to assess diagnostic accuracy.ResultsPlasma Aβ₄₂ with the level of 9.6 pg/ml showed moderate diagnostic accuracy (AUC = 0.78, sensitivity = 69.2%, specificity = 70.6%), while its combination with MoCA-INA Score improved accuracy (adjusted AUC = 0.93, sensitivity = 80.0%, specificity = 84.0%). No significant correlation was found between plasma and CSF biomarkers. Plasma p-tau181 was excluded from the final composite index because it showed an unexpected direction of change.ConclusionsPlasma Aβ₄₂ combined with MoCA-INA as a composite index, demonstrated potential diagnostic performance for AD in resource-limited settings. However, these exploratory findings should be interpreted cautiously and require further validation in larger and independent cohorts before clinical application.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261497299"},"PeriodicalIF":3.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149194102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}