Journal of Alzheimer's Disease最新文献

{"title":"Predicting future risk of developing cognitive impairment using ambulatory sleep EEG: Integrating univariate analysis and multivariate information theory approach.","authors":"Shahab Haghayegh, Ruben Herzog, David A Bennett, Susan Redline, Kristine Yaffe, Katie L Stone, Agustin Ibáñez, Kun Hu","doi":"10.1177/13872877251319742","DOIUrl":"https://doi.org/10.1177/13872877251319742","url":null,"abstract":"<p><strong>Background: </strong>Early identification of individuals at risk for cognitive impairment is crucial, as the preclinical phase offers an opportunity for interventions to slow disease progression and improve outcomes.</p><p><strong>Objective: </strong>While sleep electroencephalography (EEG) has shown significant promise in detecting cognitive impairment, this study aims to 1) develop and validate overnight EEG biomarkers for the prediction of future cognitive impairment risk, 2) assess their predictive performance within 5 years, and 3) explore the feasibility of using wearable, low-density EEG devices for convenient at-home monitoring.</p><p><strong>Methods: </strong>Overnight polysomnography was performed on 281 cognitively normal women in the Study of Osteoporotic Fractures (SOF). Cognitive reassessments were conducted approximately five years later. Features such as relative EEG power across different frequency bands and channel interactions, quantified using generalized mutual information measures, were extracted and used as inputs for machine learning models. Binary classification models distinguished participants who developed cognitive impairment from those who remained cognitively normal. Optimal feature subsets and frequency bands for classiffiation were identifed, with additional analyses testing the contribution of demographic data, sleep macrostructure, and <i>APOE</i> genotype.</p><p><strong>Results: </strong>The optimal model, utilizing univariate and multivariate EEG features, achieved an AUC of 0.76. Features from the N3 sleep stage and gamma band exhibited the largest effect sizes. Adding demographics, sleep macrostructure, and <i>APOE</i> genotype did not enhance performance.</p><p><strong>Conclusions: </strong>Overnight EEG analyses demonstrate a promising, cost-effective approach for early cognitive impairment risk assessment. Larger studies with more diverse populations are required to validate and expand these findings in diverse populations.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251319742"},"PeriodicalIF":3.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542095","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":"Effects of exercise on older adults with mild cognitive impairment: A systematic review and network meta-analysis.","authors":"Mingyuan Jia, Fengting Hu, Yuxuan Hui, Jin Peng, Weiran Wang, Jia Zhang","doi":"10.1177/13872877251321176","DOIUrl":"https://doi.org/10.1177/13872877251321176","url":null,"abstract":"<p><p><b>Background:</b> Mild cognitive impairment (MCI) represents a transitional stage between normal aging and Alzheimer's disease (AD), with a significantly elevated risk of progressing to AD. In recent years, accumulating evidence has indicated that exercise interventions may mitigate cognitive decline in individuals with MCI and reduce the risk of conversion to AD, potentially through mechanisms such as enhancing cerebral blood flow and promoting neuroplasticity. <b>Objective:</b> To explore which type of exercise is most effective in improving global cognition in older adults with MCI and to investigate whether exercise can enhance their balance abilities. <b>Methods:</b> Randomized controlled trials were retrieved from four databases. Stata software was used for Network Meta-Analysis and traditional meta-analysis. <b>Results:</b> A total of 33 studies were included, of which 28 were used to determine the best exercise modality. The results indicated that multicomponent exercise (SUCRA = 76.5%) and moderate-intensity aerobic exercise (SUCRA = 73.6%) are two effective modalities. The results of the traditional meta-analysis showed that exercise combined with cognitive training, moderate-intensity aerobic exercise, resistance exercise, and land-based kayaking training can improve balance ability. <b>Conclusions:</b> Multicomponent exercise may be the optimal exercise modality for enhancing global cognition in older adults with MCI, and various exercise modalities can improve balance abilities. However, more studies with larger sample sizes and higher quality are needed to provide further evidence.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251321176"},"PeriodicalIF":3.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537133","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":"Multimodal magnetic resonance imaging analysis of early mild cognitive impairment.","authors":"Shuai Xu, Yingao Fan, Chenglu Mao, Zheqi Hu, Zhiyuan Yang, Longjie Qu, Yun Xu, Linjie Yu, Xiaolei Zhu","doi":"10.1177/13872877251321187","DOIUrl":"https://doi.org/10.1177/13872877251321187","url":null,"abstract":"<p><strong>Background: </strong>Early mild cognitive impairment (EMCI) represents a prodromal stage of dementia, and early detection is crucial for delaying dementia progression. However, accurately identifying its neuroimaging features remains challenging.</p><p><strong>Objective: </strong>To comprehensively evaluate structural and functional neuroimaging changes in EMCI using multimodal magnetic resonance imaging (MRI) techniques.</p><p><strong>Methods: </strong>One hundred and eleven participants were included from the Alzheimer's Disease Neuroimaging Initiative (ADNI): 36 with cognitively normal (CN), 30 with EMCI, 32 with late mild cognitive impairment (LMCI), and 13 with Alzheimer's disease (AD). FreeSurfer software was employed to segment hippocampal and amygdala subregions. The amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), and functional connectivity were processed using Data Processing & Analysis for Brain Imaging toolbox. Graph Theoretical Network Analysis toolbox was utilized to evaluate global functional network.</p><p><strong>Results: </strong>The volume of most hippocampal and amygdala subregions was decreased in AD group than those of EMCI group in structural MRI. Significant differences were found between EMCI and AD group in fALFF (right insula) and ReHo (bilateral caudate regions). EMCI group exhibited stronger functional connectivity between left hippocampus and right inferior temporal gyrus (compared to CN), left inferior temporal gyrus (compared to LMCI), and cerebellum crus 8 (compared to AD). EMCI group exhibited stronger connectivity between right hippocampus and left anterior cingulate gyrus compared to AD. Network metrics showed no significant differences among these groups, but all exhibited small-world properties.</p><p><strong>Conclusions: </strong>Multimodal MRI analysis revealed the neuroimaging characteristics of EMCI and promoted the understanding of the mechanisms underlying neuroimaging changes in EMCI.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251321187"},"PeriodicalIF":3.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542091","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":"Measures of retinal health successfully capture risk for Alzheimer's disease and related dementias at midlife.","authors":"Ashleigh Barrett-Young, Aaron Reuben, Avshalom Caspi, Kirsten Cheyne, David Ireland, Jesse Kokaua, Sandhya Ramrakha, Yih-Chung Tham, Reremoana Theodore, Graham Wilson, Tien Yin Wong, Terrie Moffitt","doi":"10.1177/13872877251321114","DOIUrl":"https://doi.org/10.1177/13872877251321114","url":null,"abstract":"<p><strong>Background: </strong>Identification of at-risk individuals who would benefit from early intervention for Alzheimer's disease and related dementias (ADRD) is critical as new treatments are developed. Measures of retinal health could offer accessible and low-cost indication of pre-morbid disease risk, but their association with ADRD risk is unknown.</p><p><strong>Objective: </strong>To determine whether midlife retinal neuronal and microvascular measures are associated with ADRD risk-index scores and individual domains of ADRD risk.</p><p><strong>Methods: </strong>Data were from the Dunedin Multidisciplinary Health and Development Study, a population-representative longitudinal New Zealand-based birth cohort study. 94.1% (N = 938) of living Study members were seen at age 45 (2017-2019). Retinal neuronal (retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL)) and microvascular (arterioles and venules) measures were used as predictors. Outcome measures were four top ADRD risk indexes (CAIDE, LIBRA, Lancet, and ADU-ADRI), and a comprehensive midlife ADRD risk index, the DunedinARB.</p><p><strong>Results: </strong>Poorer retinal microvascular health (narrower arterioles and wider venules) was associated with greater ADRD risk (βs = 0.16-0.31; <i>p</i>s < 0.001). Thinner RNFL was modestly associated with higher ADRD risk (βs = 0.05-0.08; <i>p</i>s = 0.02-0.13). Follow-up tests of distinct domains of ADRD risk indicated that while RNFL associations reflected cardiometabolic risk only, microvascular measures were associated with diverse ADRD risk factors.</p><p><strong>Conclusions: </strong>Measures of retinal health, particularly microvascular measures, successfully capture ADRD risk across several domains of known risk factors, even at the young midlife age of 45 years. Retinal microvascular imaging may be an accessible, scalable, and relatively low-cost method of assessing ADRD risk among middle-aged adults.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251321114"},"PeriodicalIF":3.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542084","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":"Validation of the Cognitive-Emotional Perspective Taking test in patients with neurodegeneration.","authors":"Jonathan Adrián Zegarra-Valdivia, Tal Shany-Ur, Myrthe Gwen Rijpma, Patrick Callahan, Pardis Poorzand, Scott Grossman, Bailey McEachen, Joel H Kramer, Bruce L Miller, Katherine P Rankin","doi":"10.1177/13872877251317683","DOIUrl":"https://doi.org/10.1177/13872877251317683","url":null,"abstract":"<p><strong>Background: </strong>Theory of mind (ToM) is crucial for socioemotional interaction. ToM deficits may explain behavioral changes in dementia, especially Alzheimer's disease (AD) and frontotemporal dementia (FTD).</p><p><strong>Objective: </strong>This study examined the psychometrics of a new ToM test in healthy adults, identified ToM differences in dementia syndromes, and assessed if ToM scores predict neuropsychiatric function and real-life behavior.</p><p><strong>Methods: </strong>The UCSF Cognitive and Emotional Perspective Taking Test (CEPT) was evaluated in 195 healthy adults (age: 42.69 ± 16.20) and in a clinic cohort of 304 participants (age: 64.07 ± 9.2). Participants included healthy controls, AD, behavioral-variant frontotemporal dementia (bvFTD), semantic variant primary progressive aphasia (svPPA), non-fluent PPA (nfvPPA), and progressive supranuclear palsy (PSP) patients. CEPT's psychometrics were assessed, and ToM differences and predictions of neuropsychiatric symptoms were analyzed using regression models.</p><p><strong>Results: </strong>In controls, CEPT showed good validity and reliability. In patients, CEPT scores correlated with executive and emotional measures, but not language measures, showing good construct validity. Cognitive ToM was most impaired in AD and bvFTD, with less impairment in svPPA and PSP, and all patient groups showed impaired emotional ToM. ToM performance predicted real-life neuropsychiatric behavior, including anxiety, apathy, disinhibition, and aberrant motor behaviors.</p><p><strong>Conclusions: </strong>ToM deficits appear early in dementia syndromes and predict neuropsychiatric behavior. Assessing ToM and social cognition with ecologically valid tasks may help identify altered social cognition in early neurodegeneration.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251317683"},"PeriodicalIF":3.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537156","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":"Genetic geroscience and Alzheimer's disease: The pleiotropy is the point!","authors":"Michelle Shardell, Chixiang Chen","doi":"10.1177/13872877251321182","DOIUrl":"https://doi.org/10.1177/13872877251321182","url":null,"abstract":"<p><p>Geroscience aims to understand how the biology of aging serves as a shared contributor to multiple age-related health conditions. Genetic variants that influence multiple traits are said to exert pleiotropic effects. The study by Pan and colleagues applied a modern statistical model to identify genetic variants with potentially pleiotropic effects by assessing their joint association with Alzheimer's disease and related dementias and another age-related comorbidity (e.g., coronary heart disease, hyperlipidemia, cancer). Motivated by Pan and colleagues, this commentary introduces the concept of genetic geroscience as a paradigm for identifying genetic variants with potentially pleotropic effects on multiple age-related health conditions.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251321182"},"PeriodicalIF":3.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537136","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 of mid-age Life's Essential 8 score with digital cognitive performance and incident Alzheimer's disease: The Framingham Heart Study.","authors":"Jian Yang, Huitong Ding, Yi Li, Ting Fang Alvin Ang, Sherral Devine, Yulin Liu, Wendy Qiu, Rhoda Au, Jiantao Ma, Chunyu Liu","doi":"10.1177/13872877251317734","DOIUrl":"https://doi.org/10.1177/13872877251317734","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular health (CVH) is a modifiable risk factor for Alzheimer's disease (AD). However, studies examining the association between mid-age CVH, as indicated by Life's Essential 8 (LE8) health metrics, and digital cognitive performance or AD risk are limited.</p><p><strong>Objective: </strong>To examine the associations between mid-age CVH, assessed by LE8 scores during ages 45 to 65, and digital Clock Drawing Test (dCDT) performance as well as the incidence of AD.</p><p><strong>Methods: </strong>We included 1198 participants (51.6% women) from the Framingham Heart Study (FHS) Offspring cohort. Linear regression and Cox proportional hazards models were applied to examine the associations between mid-age CVH and dCDT performance, as well as the incidence of AD.</p><p><strong>Results: </strong>Over a median follow-up of 17.5 years, 45 participants developed AD. Each standard deviation (SD) higher mid-age LE8 total score was associated with a 0.16 SD higher level of the dCDT total score (p < 0.001) and a 0.35-fold lower risk of incident AD (HR = 0.65, 95% CI: 0.49-0.87, p = 0.003). The dCDT measures showed stronger associations with mid-age LE8 and AD risk compared to the conventional CDT (cCDT). For example, the drawing score on copy tasks was more strongly associated with LE8 (beta = 0.10, p = 0.007 versus beta = 0.08, p = 0.27) and had higher discrimination for incident AD (C-statistic = 0.89 versus 0.83) compared to the cCDT.</p><p><strong>Conclusions: </strong>Our results highlight the potential of digital cognitive assessments for evaluating AD risk and emphasize the importance of mid-age CVH in shaping cognitive outcomes and the development of AD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251317734"},"PeriodicalIF":3.4,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537132","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":"IL-34/TREM2 modulates microglia-mediated inflammation and provides neuroprotection in a mouse model of sporadic Alzheimer's disease.","authors":"Shi-Yao Wang, Zhi-Hang Huang, Rui Duan, Xin-Xin Fu, Jing-Wen Qi, Zi-Jian Luo, Ying-Dong Zhang, Teng Jiang","doi":"10.1177/13872877251320418","DOIUrl":"https://doi.org/10.1177/13872877251320418","url":null,"abstract":"<p><strong>Background: </strong>As a recently identified cytokine, interleukin-34 (IL-34) is predominantly produced by neurons and functions as a modulator for glial functions. Emerging evidence indicates that IL-34 exerted neuroprotective effects in Alzheimer's disease (AD), but the underlying mechanism remained elusive.</p><p><strong>Objective: </strong>To uncover the mechanisms by which IL-34 provides neuroprotection in AD.</p><p><strong>Methods: </strong>Using senescence-accelerated mouse prone substrain 8 (SAMP8) mice, a well-established model for sporadic AD, we investigated the dynamic changes in brain IL-34 concentrations during AD progression. Afterwards, SAMP8 mice received a 4-week continuous intracerebroventricular infusion of IL-34. Morris water maze test was employed to assess the spatial cognitive functions. Neuronal and synaptic markers, oxidative stress makers, pro-inflammatory cytokines and glial activation markers in the brains of SAMP8 mice were measured. Finally, amyloid-β (Aβ)₄₂-stimulated primary microglia, lentivirus-mediated gene knockdown strategy and co-immunoprecipitation assay were utilized to uncover the possible mechanisms by which IL-34 exerted neuroprotection in AD.</p><p><strong>Results: </strong>In SAMP8 mice, we revealed that brain IL-34 concentrations gradually decreased during AD progression. A 4-week continuous intracerebroventricular infusion of IL-34 rescued spatial cognitive impairments, ameliorated neuronal and synaptic damage, and suppressed oxidative stress and microglia-mediated inflammation in the brains of SAMP8 mice. Using Aβ₄₂-stimulated primary microglia, we demonstrated for the first time that IL-34 suppressed microglial NLRP3 inflammasome activation and pro-inflammatory cytokines release by interacting with triggering receptor expressed on myeloid cells 2 (TREM2), a key regulator of microglial functions.</p><p><strong>Conclusions: </strong>These findings uncover the mechanisms by which IL-34 provides neuroprotection in AD, indicating that IL-34/TREM2 signaling may represent a novel therapeutic strategy for this devastating disease.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251320418"},"PeriodicalIF":3.4,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537139","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":"Understanding causal estimates of smoking behaviors for cognitive impairment: A Mendelian randomization study.","authors":"Mingzhou Fu, Herong Wang, Erin B Ware, Kelly M Bakulski","doi":"10.1177/13872877251320562","DOIUrl":"https://doi.org/10.1177/13872877251320562","url":null,"abstract":"<p><strong>Background: </strong>Smoking has been linked to dementia, but the causal relationship has not been well established.</p><p><strong>Objective: </strong>Our study used a Mendelian randomization (MR) framework to examine the impact of different stages and kinds of smoking behavior on cognitive status.</p><p><strong>Methods: </strong>We analyzed a Health and Retirement Study sample, categorizing cognitive status into three levels (normal, cognitive impairment-no dementia, dementia) and using self-reported smoking behaviors. We used multivariable logistic regressions to examine associations and MR to examine potential causality. We used smoking polygenic scores as instruments for one-sample MR and validated through two-sample MR with genome-wide association study summary statistics.</p><p><strong>Results: </strong>Current smoking was associated with 1.33 times higher odds of cognitive impairment-no dementia (95% CI: 1.06, 1.65) in European ancestry participants (N = 7708). Among participants who had ever smoked, each 10 additional year of smoking was associated with 1.11 times higher odds of cognitive impairment-no dementia (95% CI: 1.10, 1.22). Using ever smoking polygenic score as a validated instrumental variable, we detected strong causal effects of ever smoking, current smoking, and total smoking years on cognitive impairment (all p < 0.001). Two-sample MR showed no evidence of causality between smoking behaviors and Alzheimer's disease. No causality was observed in the African ancestry sample (N = 1928).</p><p><strong>Conclusions: </strong>Smoking behavior was cross-sectionally associated with and potentially on the causal pathway of cognitive impairment-no dementia in the larger European ancestry sample. However, no associations were observed with dementia, and the findings did not replicate across ancestry groups. The causal relationship between smoking and cognitive health remains suggestive but not conclusive. Promoting smoking cessation remains a prudent public health strategy to prevent numerous health conditions, and its potential impact on cognitive health warrants further investigation.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251320562"},"PeriodicalIF":3.4,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537155","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":"Frailty in motion: Amnestic mild cognitive impairment and Alzheimer's disease cohorts display heterogeneity in multimorbidity classification and longitudinal transitions.","authors":"Linzy Bohn, Yao Zheng, G Peggy McFall, Melissa K Andrew, Roger A Dixon","doi":"10.1177/13872877251319547","DOIUrl":"https://doi.org/10.1177/13872877251319547","url":null,"abstract":"<p><strong>Background: </strong>Data-driven examination of multiple morbidities and deficits are informative for clinical and research applications in aging and dementia. Resulting profiles may change longitudinally according to dynamic alterations in extent, duration, and pattern of risk accumulation. Do such frailty-related changes include not only progression but also stability and reversion?</p><p><strong>Objective: </strong>With cognitively impaired and dementia cohorts, we employed data-driven analytics to (a) detect the extent of heterogeneity in frailty-related multimorbidity and deficit burden subgroups and (b) identify key person characteristics predicting differential transition patterns.</p><p><strong>Methods: </strong>We assembled baseline and 2-year follow-up data from the National Alzheimer's Coordinating Center for amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) cohorts. We applied factor analyses to 43 multimorbidity and deficit indicators. Latent Transition Analysis (LTA) was applied to the resulting domains in order to detect subgroups differing in transition patterns for multimorbidity and deficit burden. We characterized heterogeneity in change patterns by evaluating key person characteristics as differential predictors.</p><p><strong>Results: </strong>Factor analyses revealed five domains at two time points. LTA showed that two latent burden subgroups at Time 1 (<i>Low</i>, <i>Moderate</i>) differentiated into an additional two subgroups at Time 2 (adding <i>Mild, Severe</i>). Transition analyses detected heterogeneous changes, including progression, stability, and reversion. Baseline classifications and transitions varied according to clinical cohort, global cognition, sex, age, and education.</p><p><strong>Conclusions: </strong>Heterogeneous frailty-related subgroup transitions can be (a) detected in aging adults living with aMCI and AD, (b) characterized as not only progression but also stability and reversion, and (c) predicted by precision characteristics.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251319547"},"PeriodicalIF":3.4,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537135","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}