Qu Tian, Erin E. Greig, Keenan A. Walker, Michael R. Duggan, Zhijian Yang, Abhay Moghekar, Bennett A. Landman, Christos Davatzikos, Susan M. Resnick, Luigi Ferrucci
{"title":"Longitudinal patterns of brain aging and neurodegeneration among older adults with dual decline in memory and gait","authors":"Qu Tian, Erin E. Greig, Keenan A. Walker, Michael R. Duggan, Zhijian Yang, Abhay Moghekar, Bennett A. Landman, Christos Davatzikos, Susan M. Resnick, Luigi Ferrucci","doi":"10.1002/alz.14612","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> INTRODUCTION</h3>\n \n <p>Dual cognitive and mobility decline is more strongly associated with dementia risk than cognitive decline only. It remains unknown whether this syndrome is associated with brain atrophy patterns, white matter (WM) damage, or pathology.</p>\n </section>\n \n <section>\n \n <h3> METHODS</h3>\n \n <p>In the Baltimore Longitudinal Study of Aging participants with and without dual decline, we used linear mixed-effects models to compare up to 13-year longitudinal changes in MRI-derived atrophy patterns, WM hyperintensities (<i>n</i> = 339), microstructure (<i>n</i> = 307), plasma glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), amyloid beta 42/40 (Aβ<sub>42/40</sub>) ratio (<i>n</i> = 349), and phosphorylated tau 181 (pTau181) (<i>n</i> = 258).</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>Those experiencing dual decline showed accelerated atrophy in medial temporal (<i>p</i> = .004), parietotemporal (<i>p</i> = .029), and perisylvian regions (<i>p</i> = .028), whereas gait decline only showed accelerated parietotemporal atrophy (<i>p</i> = .035) and memory decline only showed perisylvian atrophy (<i>p</i> = .021). Dual decline was also associated with unique microstructural deterioration in several WM tracts (<i>p</i> < .05), a greater decrease in Aβ<sub>42/40</sub> ratio (<i>p</i> = .015), and greater increases in GFAP (<i>p</i> = .009) and NfL (<i>p</i> < .001).</p>\n </section>\n \n <section>\n \n <h3> DISCUSSION</h3>\n \n <p>Individuals experiencing dual decline are at an increased risk for regional brain atrophy, microstructural degradation, and biomarker-defined molecular changes underlying dementia.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>Those experiencing dual decline showed several accelerated brain atrophy patterns.</li>\n \n <li>Those experiencing dual decline showed unique microstructural deterioration.</li>\n \n <li>Dual decline showed a greater decline in plasma Aβ<sub>42/40</sub> ratio.</li>\n \n <li>Dual decline showed greater increases in plasma GFAP and NfL.</li>\n \n <li>Dual decline may indicate brain and blood markers underlying dementia.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 2","pages":""},"PeriodicalIF":13.0000,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14612","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer's & Dementia","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/alz.14612","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
INTRODUCTION
Dual cognitive and mobility decline is more strongly associated with dementia risk than cognitive decline only. It remains unknown whether this syndrome is associated with brain atrophy patterns, white matter (WM) damage, or pathology.
METHODS
In the Baltimore Longitudinal Study of Aging participants with and without dual decline, we used linear mixed-effects models to compare up to 13-year longitudinal changes in MRI-derived atrophy patterns, WM hyperintensities (n = 339), microstructure (n = 307), plasma glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), amyloid beta 42/40 (Aβ42/40) ratio (n = 349), and phosphorylated tau 181 (pTau181) (n = 258).
RESULTS
Those experiencing dual decline showed accelerated atrophy in medial temporal (p = .004), parietotemporal (p = .029), and perisylvian regions (p = .028), whereas gait decline only showed accelerated parietotemporal atrophy (p = .035) and memory decline only showed perisylvian atrophy (p = .021). Dual decline was also associated with unique microstructural deterioration in several WM tracts (p < .05), a greater decrease in Aβ42/40 ratio (p = .015), and greater increases in GFAP (p = .009) and NfL (p < .001).
DISCUSSION
Individuals experiencing dual decline are at an increased risk for regional brain atrophy, microstructural degradation, and biomarker-defined molecular changes underlying dementia.
Highlights
Those experiencing dual decline showed several accelerated brain atrophy patterns.
Those experiencing dual decline showed unique microstructural deterioration.
Dual decline showed a greater decline in plasma Aβ42/40 ratio.
Dual decline showed greater increases in plasma GFAP and NfL.
Dual decline may indicate brain and blood markers underlying dementia.
期刊介绍:
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.