Idris Demirsoy, Elham Ghanbarian, Babak Khorsand, Bhargav T Nallapu, Kellen K Petersen, Richard B Lipton, S Ahmad Sajjadi, Laura A Rabin, Ali Ezzati
{"title":"A4研究中认知功能指数的项目水平反应与tau病理和海马体积的关系。","authors":"Idris Demirsoy, Elham Ghanbarian, Babak Khorsand, Bhargav T Nallapu, Kellen K Petersen, Richard B Lipton, S Ahmad Sajjadi, Laura A Rabin, Ali Ezzati","doi":"10.1002/dad2.70128","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease (AD) has a long preclinical phase in which individuals may accumulate amyloid beta (Aβ) and tau pathology without noticeable cognitive impairment. Subjective cognitive impairment reports can provide early insights into cognitive decline.</p><p><strong>Methods: </strong>In the A4 Study, 339 cognitively unimpaired, Aβ-positive individuals underwent tau positron emission tomography imaging. Tau status was classified based on medial temporal lobe tau standardized uptake value ratios (tau<sub>MTL</sub>). Participants and study partners assessed cognitive changes using the 15-item Cognitive Function Index (CFI) questionnaire. We explored the relationship among tau<sub>MTL</sub>, hippocampal volume (HVa), and CFI reports.</p><p><strong>Results: </strong>Higher tau<sub>MTL</sub> was associated with participant-reported concerns about memory and navigation, and with study partner-reported difficulty remembering appointments. Lower HVa showed a marginal association with participant-reported driving difficulty.</p><p><strong>Discussion: </strong>These findings support the utility of participant- and study partner-reported concerns as early indicators of preclinical AD pathology, with potential value for early detection and trial enrichment strategies.</p><p><strong>Highlights: </strong>Higher tau in the medial temporal lobe (tau<sub>MTL</sub>) was linked to participant-reported memory and orientation decline such as needing reminders or getting lost.Higher tau<sub>MTL</sub> was associated with increased memory-related concerns, such as needing help with appointments and asking repetitive questions.Lower hippocampal volume was associated with spatial memory and navigation such as driving difficulties and greater memory decline as reported by study partners.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"17 2","pages":"e70128"},"PeriodicalIF":4.4000,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12177208/pdf/","citationCount":"0","resultStr":"{\"title\":\"Association of item-level responses to cognitive function index with tau pathology and hippocampal volume in the A4 Study.\",\"authors\":\"Idris Demirsoy, Elham Ghanbarian, Babak Khorsand, Bhargav T Nallapu, Kellen K Petersen, Richard B Lipton, S Ahmad Sajjadi, Laura A Rabin, Ali Ezzati\",\"doi\":\"10.1002/dad2.70128\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Alzheimer's disease (AD) has a long preclinical phase in which individuals may accumulate amyloid beta (Aβ) and tau pathology without noticeable cognitive impairment. Subjective cognitive impairment reports can provide early insights into cognitive decline.</p><p><strong>Methods: </strong>In the A4 Study, 339 cognitively unimpaired, Aβ-positive individuals underwent tau positron emission tomography imaging. Tau status was classified based on medial temporal lobe tau standardized uptake value ratios (tau<sub>MTL</sub>). Participants and study partners assessed cognitive changes using the 15-item Cognitive Function Index (CFI) questionnaire. We explored the relationship among tau<sub>MTL</sub>, hippocampal volume (HVa), and CFI reports.</p><p><strong>Results: </strong>Higher tau<sub>MTL</sub> was associated with participant-reported concerns about memory and navigation, and with study partner-reported difficulty remembering appointments. Lower HVa showed a marginal association with participant-reported driving difficulty.</p><p><strong>Discussion: </strong>These findings support the utility of participant- and study partner-reported concerns as early indicators of preclinical AD pathology, with potential value for early detection and trial enrichment strategies.</p><p><strong>Highlights: </strong>Higher tau in the medial temporal lobe (tau<sub>MTL</sub>) was linked to participant-reported memory and orientation decline such as needing reminders or getting lost.Higher tau<sub>MTL</sub> was associated with increased memory-related concerns, such as needing help with appointments and asking repetitive questions.Lower hippocampal volume was associated with spatial memory and navigation such as driving difficulties and greater memory decline as reported by study partners.</p>\",\"PeriodicalId\":53226,\"journal\":{\"name\":\"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring\",\"volume\":\"17 2\",\"pages\":\"e70128\"},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2025-06-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12177208/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1002/dad2.70128\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/4/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/dad2.70128","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Association of item-level responses to cognitive function index with tau pathology and hippocampal volume in the A4 Study.
Introduction: Alzheimer's disease (AD) has a long preclinical phase in which individuals may accumulate amyloid beta (Aβ) and tau pathology without noticeable cognitive impairment. Subjective cognitive impairment reports can provide early insights into cognitive decline.
Methods: In the A4 Study, 339 cognitively unimpaired, Aβ-positive individuals underwent tau positron emission tomography imaging. Tau status was classified based on medial temporal lobe tau standardized uptake value ratios (tauMTL). Participants and study partners assessed cognitive changes using the 15-item Cognitive Function Index (CFI) questionnaire. We explored the relationship among tauMTL, hippocampal volume (HVa), and CFI reports.
Results: Higher tauMTL was associated with participant-reported concerns about memory and navigation, and with study partner-reported difficulty remembering appointments. Lower HVa showed a marginal association with participant-reported driving difficulty.
Discussion: These findings support the utility of participant- and study partner-reported concerns as early indicators of preclinical AD pathology, with potential value for early detection and trial enrichment strategies.
Highlights: Higher tau in the medial temporal lobe (tauMTL) was linked to participant-reported memory and orientation decline such as needing reminders or getting lost.Higher tauMTL was associated with increased memory-related concerns, such as needing help with appointments and asking repetitive questions.Lower hippocampal volume was associated with spatial memory and navigation such as driving difficulties and greater memory decline as reported by study partners.
期刊介绍：
Alzheimer''s & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM) is an open access, peer-reviewed, journal from the Alzheimer''s Association® that will publish new research that reports the discovery, development and validation of instruments, technologies, algorithms, and innovative processes. Papers will cover a range of topics interested in the early and accurate detection of individuals with memory complaints and/or among asymptomatic individuals at elevated risk for various forms of memory disorders. The expectation for published papers will be to translate fundamental knowledge about the neurobiology of the disease into practical reports that describe both the conceptual and methodological aspects of the submitted scientific inquiry. Published topics will explore the development of biomarkers, surrogate markers, and conceptual/methodological challenges. Publication priority will be given to papers that 1) describe putative surrogate markers that accurately track disease progression, 2) biomarkers that fulfill international regulatory requirements, 3) reports from large, well-characterized population-based cohorts that comprise the heterogeneity and diversity of asymptomatic individuals and 4) algorithmic development that considers multi-marker arrays (e.g., integrated-omics, genetics, biofluids, imaging, etc.) and advanced computational analytics and technologies.
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