The Journal of Prevention of Alzheimer's Disease最新文献

{"title":"Distinct spatial patterns of perivascular spaces enlargement for multiple and Co-existing pathologies of cognitive impairment.","authors":"Woosik Kim, Yejin Hwang, Yelim Yang, Min Gyeong Kim, Hyemin Jang, Seung Hong Choi, Joon-Kyung Seong, Roh-Eul Yoo, Wha Jin Lee","doi":"10.1016/j.tjpad.2026.100631","DOIUrl":"10.1016/j.tjpad.2026.100631","url":null,"abstract":"<p><strong>Background: </strong>This study examines how amyloid-β and vascular pathology independently and jointly relate to regional perivascular space (PVS) burden on T2-weighted MRI.</p><p><strong>Methods: </strong>In 307 cognitively impaired participants retrospectively identified from the Seoul National University dementia cohort, PVS were automatically quantified in the basal ganglia (BG) and lobar white matter regions from 2D T2-weighted MRI. Amyloid-β and vascular pathology positivity were defined by [18F]Florbetaben PET and small vessel disease markers. Group differences among pathology-negative (n=36), vascular-only (n=106), amyloid-only (n=48), and mixed (n=117) subgroups, as well as amyloid-vascular interactions, were assessed using analysis of covariance and multivariable linear regression.</p><p><strong>Results: </strong>BG PVS were greater in participants with vascular burden than in pathology-negative participants (F=26.97, p<0.001; Cohen's d=1.28), independent of amyloid-β. Lobar PVS were higher in single-pathology than pathology-negative participants across the parietal, temporal, and occipital regions (F=8.25-18.04, Cohen's d=0.66-0.98, all p≤0.014), with no additional increase in the mixed group. Greater amyloid-β retention was associated with parietal, temporal, and occipital PVS in VB- participants (β [95% CI]=0.55 [0.19, 0.92], 0.69 [0.35, 1.02], 0.40 [0.16, 0.64], respectively). Among AB- participants, vascular burden was associated with BG PVS (β [95% CI]=0.65 [0.40, 0.89]). Multivariable regression demonstrated less-than-additive AB×VB interactions in parietal, temporal, and occipital PVS (β [95% CI]=-0.65 [-1.08, -0.23], -0.74 [-1.13, -0.35], -0.42 [-0.70, -0.14], respectively).</p><p><strong>Conclusions: </strong>Distinct regional PVS patterns reflect spatially selective and severity-dependent glymphatic-related structural alterations associated with amyloid-β and vascular pathologies, supporting PVS as a quantitative imaging biomarker for disentangling mixed pathways of cognitive impairment.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 8","pages":"100631"},"PeriodicalIF":7.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13355189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148370129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a CD44-dependent control of astrocytic autophagic activity in Alzheimer's disease.","authors":"Haiyan Wang, Ying Long, Yu Tang, Lijie Duan, Zijie Wang, Shuzhen Zhang, Yanqing Yin, Jiawei Zhou, Wenjuan Wu, Chunjiu Zhong","doi":"10.1016/j.tjpad.2026.100601","DOIUrl":"10.1016/j.tjpad.2026.100601","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory impairment. Despite extensive research, the precise molecular mechanisms driving AD pathogenesis remain incompletely understood. This study sought to identify robust molecular targets and cellular basis underlying AD progression.</p><p><strong>Methods: </strong>We performed a systematic analysis of cross-regional transcriptomic datasets from AD patients, integrating differential expression analysis across 14 Gene Expression Omnibus (GEO) datasets with cross-regional intersection mapping. Single-nucleus RNA sequencing (snRNA-seq) was employed to resolve cell-type-specific expression patterns. Furthermore, cellular communication analysis and functional enrichment of astrocyte-specific genes were conducted. The biological role of the identified candidate was validated in vitro using Aβ42 oligomer-treated primary astrocytes via siRNA-mediated knockdown and plasmid-driven overexpression, with autophagic activity assessed through LC3-II and p62 expression.</p><p><strong>Results: </strong>The transmembrane glycoprotein receptor CD44 was identified as consistently upregulated across AD-vulnerable brain regions, including the temporal cortex, frontal cortex, entorhinal cortex, and hippocampus. snRNA-seq analysis identified this upregulation primarily to astrocytes. Intercellular signaling analysis indicated that the CD44-SPP1 axis enhanced astrocyte-glial crosstalk. Functional enrichment analysis linked astrocytic CD44 to the modulation of autophagy pathways. In vitro experiments demonstrated that CD44 knockdown promoted autophagic activation (increased LC3-II and decreased p62), whereas CD44 overexpression suppressed autophagic activity.</p><p><strong>Conclusion: </strong>Our findings establish CD44 as a pivotal regulator of astrocytic autophagy in AD, highlighting its potential as a novel therapeutic target.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 8","pages":"100601"},"PeriodicalIF":7.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13199780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147983316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The time interval from amyloid to tau PET positivity varies by age, sex and APOE-ε4 status.","authors":"Marta Milà-Alomà, Isabella Hausle, Kellen K Petersen, Pamela Thropp, Suzanne E Schindler, Duygu Tosun","doi":"10.1016/j.tjpad.2026.100622","DOIUrl":"10.1016/j.tjpad.2026.100622","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) progression varies widely among individuals. Identifying factors influencing timing of pathology and clinical progression is crucial for optimizing early intervention trials.</p><p><strong>Objectives: </strong>To investigate how the estimated age at amyloid and tau PET positivity, and the time interval between these two key events (\"amyloid-tau time interval\"), relate to symptom onset and clinical progression, and to assess the effects of APOE-ε4 status and sex on these associations.</p><p><strong>Design: </strong>This analysis used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Harvard Aging Brain Study (HABS).</p><p><strong>Setting: </strong>The ADNI is a multicenter observational cohort conducted at 55 sites across the United States; The HABS is a longitudinal, single-center observational cohort.</p><p><strong>Participants: </strong>This study included participants with at least one positive amyloid PET scan (ADNI n = 792; HABS n = 104) or at least one positive tau PET scan (ADNI n = 212; HABS n = 48). All participants had information on sex, APOE-ε4 status, and longitudinal cognitive assessments.</p><p><strong>Measurements: </strong>We examined the influence of APOE-ε4 status, sex, and their interaction on the estimated age at biomarker positivity and the amyloid-tau time interval. Accelerated Failure Time (AFT) models were used to predict time to symptom onset (CDR > 0) based on estimated biomarker positivity age and the amyloid-tau time interval. Linear mixed-effects (LME) models evaluated differences in the rate of cognitive decline, as measured by CDR-SB, over five years following symptom onset according to estimated biomarker positivity age and amyloid-tau time interval. Additional models included interaction terms with sex or APOE-ε4 status.</p><p><strong>Results: </strong>The amyloid-tau time interval varied markedly between individuals and was shorter in APOE-ε4 carriers, women, and those with older age at amyloid PET positivity. APOE-ε4 carriers and women became amyloid and tau PET positive at younger ages. Following amyloid PET positivity, a shorter time to tau PET positivity predicted earlier symptom onset. After symptom onset, faster cognitive decline was observed in individuals with younger ages at amyloid or tau PET positivity. The time to symptom onset following tau PET positivity, or the rate of cognitive decline after symptom onset, were not influenced by the amyloid-tau time interval.</p><p><strong>Conclusions: </strong>After becoming amyloid PET positive, APOE-ε4 carriers, women and older individuals may have a shorter window for detection and treatment before they become tau PET positive and develop symptoms. These findings should guide the identification of individuals at highest risk of rapid AD progression, enabling more efficient participant selection for clinical trials.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 8","pages":"100622"},"PeriodicalIF":7.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13284470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148272968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can we identify people with Alzheimer's disease from examination of the eye? A bidirectional Mendelian randomization (MR) study.","authors":"Humayun Kiser, Ashley Budu-Aggrey, Jessica N Cooke Bailey, Ana Villaplana-Velasco, Miguel O Bernabeu, Xiaofan Jiang, Christopher G Owen, Jonathan L Haines, Louis R Pasquale, Stuart MacGregor, Xiaoyi Raymond Gao, Janey L Wiggs, Chen Jiang, Hélène Choquet, George Davey Smith, Patrick G Kehoe, Neil M Davies, Aimee L Hanson, Emma L Anderson, Denize Atan","doi":"10.1016/j.tjpad.2026.100635","DOIUrl":"10.1016/j.tjpad.2026.100635","url":null,"abstract":"<p><strong>Background: </strong>Neurodegeneration in Alzheimer's disease (AD) is thought to be driven by amyloid-beta and tau deposition in the cerebral vasculature and brain. As the eye is an extension of the central nervous system, this study aimed to determine which neurovascular and neuroretinal changes in the eye are caused by AD rather than associations of the disease.</p><p><strong>Methods: </strong>Bidirectional two-sample univariable and multivariable Mendelian randomization (MR) methods were applied. Instrumental variables were derived from genome-wide association studies (GWAS) of AD and the following ocular features: thickness measurements of central macula (MT), retinal nerve fibre layer (mRNFL), ganglion cell-inner plexiform layer (mGCIPL), outer nuclear layer (ONL), inner segment layer (IS), and outer segment (OS) from macular region OCT scans; arteriolar tortuosity (AT), venular tortuosity (VT), venular width (VW), fractal dimension (FD), vertical cup-to-disc ratio (VCDR), optic cup area (OCA), and optic disc area (ODA) derived from other imaging methods.</p><p><strong>Results: </strong>There was strong evidence that genetic liability to AD affected the retinal vasculature by specifically increasing AT (β = 0.007;95%CI=0.002,0.011;p-value=0.005) in UK Biobank participants (n=52,798). AD may influence the mRNFL (β=-0.047,95%CI=-0.119,0.023,p-value=0.18) and mGCIPL (β=-0.061;95%CI=-0.14,0.025,p-value=0.16) of the inner retina and OS layer (β = 0.044;95%CI=-0.0001,0.08;p-value=0.05) but the evidence was weak. Multivariable MR analysis showed that a causal relationship between optic disc area and AD (OR=0.76;95%CI=0.62,0.93,p-value=0.009) was probably mediated by refractive error.</p><p><strong>Conclusion: </strong>Early cerebrovascular signs of AD may be detected by examination of the eye. Further investigation is required to determine the clinical utility of eye screening for dementia.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 8","pages":"100635"},"PeriodicalIF":7.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glymphatic dysfunction, plasma neurofilament light, and cortical free water mediate cognitive decline in familial frontotemporal lobar degeneration.","authors":"Meiling Qiu, Li Ding, Rui Bao, Juanyu Gong, Wencai Ding, Zhiding Shao, Yongsheng Han","doi":"10.1016/j.tjpad.2026.100639","DOIUrl":"10.1016/j.tjpad.2026.100639","url":null,"abstract":"<p><strong>Background: </strong>Familial frontotemporal lobar degeneration (f-FTLD) is the second most common form of young-onset dementia, with diverse clinical presentations, neuropathological substrates and genetic backgrounds. While evidence suggests that glymphatic dysfunction, neuroaxonal injury, and cortical microstructural alterations may jointly contribute to f-FTLD, their interrelationships across genotypes remain unclear.</p><p><strong>Objectives: </strong>This study aims to investigate the roles of glymphatic dysfunction, cortical free water (cFW), and plasma neurofilament light (NfL) in f-FTLD and examine their relationship with cognitive decline.</p><p><strong>Design: </strong>A multimodal approach was applied, involving diffusion tensor imaging along the perivascular space (DTI-ALPS) for glymphatic function, plasma NfL measurement, and voxel-wise cortical free water mapping. Analyses comparing FTLD mutation groups and serial mediation analyses were conducted in 322 participants (C9orf72, GRN, MAPT mutation carriers, and matched controls).</p><p><strong>Setting: </strong>This study was conducted across multiple participating centers using standardized imaging protocols and harmonized multi-site data.</p><p><strong>Participants: </strong>A total of 322 participants were included: 87 C9orf72 expansion carriers, 56 GRN mutation carriers, 58 MAPT mutation carriers, and 121 healthy controls.</p><p><strong>Intervention: </strong>No intervention was applied in this observational study. Participants underwent genetic testing, cognitive assessment, and diffusion MRI scans; plasma NfL was available for mutation carriers.</p><p><strong>Measurements: </strong>Glymphatic function was assessed using DTI-ALPS, plasma NfL levels were measured to reflect neuroaxonal injury, and cortical microstructure was assessed through cortical free water (cFW) mapping.</p><p><strong>Results: </strong>Significant reductions in DTI-ALPS and elevations in cFW were observed in C9orf72 and GRN mutation carriers, with strong associations to clinical cognitive decline. Plasma NfL levels were highest in GRN mutation carriers and correlated strongly with cognitive severity. Mediation analysis indicated that the pathway linking DTI-ALPS to cognition through NfL explained a substantial portion of the indirect effect, while residual direct effects suggested that additional mechanisms also contribute to cognitive decline.</p><p><strong>Conclusions: </strong>This study identifies glymphatic dysfunction as a key factor contributing to cognitive decline in f-FTLD, with plasma NfL serving as an important partial mediator and cFW providing additional region-specific information.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 8","pages":"100639"},"PeriodicalIF":7.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13348048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148388244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suboptimal adherence to brain health recommendations in patients pursuing anti-amyloid antibody therapy for Alzheimer's disease: Report from the Brain Health Vital Signs project.","authors":"Kirk R Daffner, Kayla Riera, George R Ghorayeb, Brittany M McFeeley, Emma Weizenbaum, Kim Willment, Seth A Gale","doi":"10.1016/j.tjpad.2026.100640","DOIUrl":"10.1016/j.tjpad.2026.100640","url":null,"abstract":"<p><strong>Background: </strong>Consensus is consolidating around a set of lifestyle and medical factors that can promote brain health and reduce the risk of dementia for older adults and further decline for those with early Alzheimer's disease (AD) and related disorders. Little is known about the degree to which recommended brain-healthy behaviors have been adopted by patients with early AD pursuing anti-amyloid antibody therapy (AAT), a proactive group interested in doing what is under their control to help preserve cognitive and functional status. Here, initial results of a clinically relevant quality improvement study are reported.</p><p><strong>Objective: </strong>To determine the extent to which patients pursuing AAT for AD adhere to consensus-based brain health recommendations.</p><p><strong>Participants: </strong>One hundred fifty patients with mild cognitive impairment (MCI) or mild dementia due to AD seeking AAT were studied and compared to a group of 117 patients with MCI or mild dementia who were not pursuing AAT.</p><p><strong>Measurements: </strong>Using a clinical survey tool developed for the project, patients were assessed on 15 modifiable risk factors for cognitive decline and dementia, including 11 via e-survey (diet, physical activity, cognitive activity, sleep, social engagement, smoking status, alcohol consumption, hearing, vision, mood/stress, and purpose in life) and 4 via electronic medical record (EMR) (blood pressure, BMI, LDL cholesterol level, and HbA1c). For each factor, the percentage of each of the two patient groups that was not optimally adhering to brain health-related guidelines was calculated. For each individual, the total number of factors not optimally being followed was determined.</p><p><strong>Results: </strong>Less than 3% of patients with early AD pursuing AAT were following or had anthropometric measures/lab values in line with all 15 brain health recommendations. The five factors with the lowest adherence rates involved physical activity, mood/stress, HbA1c, blood pressure, and BMI, with 44-63% of the AAT group suboptimally following consensus-based guidelines. For 11 of 15 factors, >25% of the group were not adhering to guidelines. No robust differences in degree or pattern of adherence to guidelines were observed between patients pursuing and not pursuing AAT. There were no data in the EMR for HbA1c in >42% of patients and for LDL in >23% of patients in either group.</p><p><strong>Conclusions: </strong>Suboptimal adherence to brain health recommendations may be common among patients with early AD, whether they are pursuing AAT or not. These results suggest that healthcare systems may need to develop more effective strategies and individualized interventions for addressing modifiable risk factors for cognitive decline and dementia, and more efficacious procedures for ensuring that relevant, actionable data associated with brain health are updated in the EMR.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 8","pages":"100640"},"PeriodicalIF":7.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From trial population to treated population: why EU-eligible subgroup analyses matter for anti-amyloid immunotherapy.","authors":"Timo Grimmer","doi":"10.1016/j.tjpad.2026.100665","DOIUrl":"10.1016/j.tjpad.2026.100665","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 8","pages":"100665"},"PeriodicalIF":7.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13571915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping the nature, type, and association network of safety incidents among individuals with cognitive impairment in China: a large-scale multicenter cross-sectional study.","authors":"Ying Zhou, Guoping Peng, Zhengluan Liao, Huayan Liu, Jun Liu, Wang Liao, Qiumin Qu, Jingping Shi, Jieli Geng, Nan Zhi, Wenwei Cao, Yaying Song, Yang Zhang, Xiaohong Wang, Lin Wang, Yuan Zhu, Yan Zhou, Huali Wang, Yongan Sun, Rujing Ren, Hengge Xie, Gang Wang","doi":"10.1016/j.tjpad.2026.100606","DOIUrl":"10.1016/j.tjpad.2026.100606","url":null,"abstract":"<p><strong>Background: </strong>Patient safety critically influences both quality of life and disease progression in older adults with cognitive impairment, yet large-scale multicenter data remain scarce. This study aims to systematically analyze the types of safety incidents experienced by patients with Alzheimer's disease and related cognitive impairments, and explore the network associations of different safety incidents.</p><p><strong>Methods: </strong>Initiated by the Alzheimer's Disease China (ADC), this survey recruited 1057 older individuals with Alzheimer's and related cognitive impairments, along with their families, across 31 provinces, autonomous regions, and municipalities. The safety incidents evaluated in this study included falls, getting lost, medication errors, verbal aggression, physical aggression, household fire, aspiration, and choking. Incidence rates for overall and specific safety incidents were calculated. Correlation analyses and network analysis were performed to examine relationships between safety incidents.</p><p><strong>Results: </strong>A high proportion (73.5%) of participants reported at least one safety incident in the past year, with over one-third (36.0%) experiencing three or more concurrent incidents. Medication errors (55.9%) and verbal aggression (39.6%) were most frequent, followed by falls (32.5%) and physical aggression (22.7%). Incidence rates varied significantly by cognitive impairment stage, care setting, and geographic region. Network analysis highlighted medication errors and getting lost as central nodes bridging other incidents.</p><p><strong>Conclusions: </strong>This study reveals an alarmingly high incidence of safety incidents among cognitively impaired patients, affecting their physical, psychological, and familial well-being. A collaborative, multidisciplinary effort involving healthcare professionals, family caregivers, fire and police emergency responders, and public health policymakers is essential to develop individualized safety strategies aligned with patient needs and contextual considerations.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 8","pages":"100606"},"PeriodicalIF":7.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13233742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148057048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tailored implementation of multidomain intervention to prevent cognitive impairment in community-dwelling older adults (Timi-Cog): A study protocol for a hybrid type 2 trial effectiveness-implementation study.","authors":"Zishuo Huang, Changmiao Shi, Erxu Xue, Gonghang Qiu, Yurong Jing, Ziyi Wang, Xinhua Ao, Dong Roman Xu, Ying Wang","doi":"10.1016/j.tjpad.2026.100623","DOIUrl":"10.1016/j.tjpad.2026.100623","url":null,"abstract":"<p><strong>Background & objectives: </strong>Despite growing recognition of multidomain non-pharmaceutical interventions (NPIs) for preventing cognitive impairment, their scalable implementation remains underdeveloped in China. This hybrid type 2 effectiveness-implementation study aims to bridge this gap by identifying implementation determinants, developing tailored strategies, and evaluating both implementation or health outcomes for multidomain NPIs and tailored strategies.</p><p><strong>Methods: </strong>This protocol describes the design of an ongoing study. The formative phase has been completed: guided by Consolidated Framework for Implementation Research (CFIR), we integrated the COM-B model from the Behaviour Change Wheel (BCW) and the Theoretical Domains Framework (TDF) into an interview guide. Key informant interviews and focus groups identified barriers/facilitators, and the CFIR-ERIC matching tool finalized the implementation strategies. Subsequently, a hybrid type 2 cluster RCT will be conducted (or is currently underway) across 13 districts in Changxing County, Zhejiang. A total of 1170 older adults and 273 community health workers (CHWs) - including general practitioners, social workers, and volunteers - will be randomized into three study arms: Arm 1 will receive evidence-based practices (EBP) combined with intrinsic motivation; Arm 2, EBP with implementation strategies; and Arm 3 (control), health education with implementation strategies. The EBP package includes cardio-metabolic risk management, cognitive training, physical activity, and nutritional counseling. Implementation uses three bundles: (1) Capacity Building and Professional Support, (2) Collaborative Implementation and Network Building, and (3) an AI-enabled WeChat mini-program (Timi-Cog). Outcomes will be assessed using the Re-AIM framework over 18 months. Statistical analysis will employ mixed-effects linear models, adjusted for baseline characteristics and clustering effects.</p><p><strong>Conclusions & implications: </strong>This theory-informed initiative addresses the dementia prevention implementation gap in China. By combining BCW/TDF frameworks with implementation science methods and employing a hybrid design, the study will generate robust evidence on both clinical effectiveness and practical implementation, informing the integration of multidomain NPIs into China's primary care system.</p><p><strong>Trial registration: </strong>Chinese Clinical Trial Registry (ChiCTR2500098587).</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 8","pages":"100623"},"PeriodicalIF":7.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13277494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148253385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drawing a line: Differentiating mild from moderate dementia using the functional activities questionnaire.","authors":"Ersin Ersözlü, Lukas Preis, Aykut Aktuz, Louise Droste, Akin Erman, Daria Gref, Katharina Sophie Strentz, Julian Hellmann-Regen","doi":"10.1016/j.tjpad.2026.100630","DOIUrl":"10.1016/j.tjpad.2026.100630","url":null,"abstract":"<p><strong>Background: </strong>Accurate differentiation between mild and moderate dementia is increasingly important, particularly as amyloid-targeting therapies are restricted to early disease stages. Functional impairment in instrumental activities of daily living is a hallmark of progression beyond mild dementia. The informant-based Functional Activities Questionnaire (FAQ) is widely used, but empirically validated cut-offs distinguishing mild from moderate dementia remain insufficiently defined.</p><p><strong>Methods: </strong>The optimal cut-off score was derived from the entire National Alzheimer's Coordinating Center (NACC) Uniform Data Set as a discovery cohort (n = 34,513) and validated in two independent multicentric cohorts (Alzheimer's Disease Neuroimaging Initiative (ADNI) n = 381 and Frontotemporal Lobar Degeneration Neuroimaging Initiative (FTLDNI) n = 74). The dementia staging was based on the Clinical Dementia Rating (CDR) global score. Functional impairment was assessed using the 10-item FAQ. Receiver operating characteristic analyses in NACC identified optimal thresholds, which were applied unchanged in validation cohorts. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated, and discordant cases were examined to identify factors associated with misclassification.</p><p><strong>Results: </strong>In NACC, the FAQ demonstrated excellent discrimination of moderate dementia (AUC=0.947, 95% CI 0.944-0.949). A cut-off value of ≥18 maximized discrimination (sensitivity 96%, specificity 87%). A higher threshold of ≥23 improved specificity (92%), while maintaining sensitivity (83%). In ADNI and FTLDNI, the sensitivity of ≥18 threshold yielded 92% and 94%, respectively. Moreover, older age and lower cognitive performance were associated with higher odds of misclassification.</p><p><strong>Conclusions: </strong>The FAQ robustly differentiates mild from moderate dementia across diverse cohorts. A threshold of ≥18 prioritizes sensitivity, whereas ≥23 favors specificity, supporting context-dependent functional staging in clinical and research settings. Individuals with FAQ scores between 18 and 22 may benefit from more detailed clinical staging.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 8","pages":"100630"},"PeriodicalIF":7.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13330517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148353558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}