Longitudinal patterns of brain aging and neurodegeneration among older adults with dual decline in memory and gait

IF 13 1区 医学 Q1 CLINICAL NEUROLOGY Alzheimer's & Dementia Pub Date : 2025-02-23 DOI:10.1002/alz.14612
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
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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.

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来源期刊
Alzheimer's & Dementia
Alzheimer's & Dementia 医学-临床神经学
CiteScore
14.50
自引率
5.00%
发文量
299
审稿时长
3 months
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.
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