Longitudinal Patterns of Brain Aging and Neurodegeneration Among Older Adults with Dual Decline in Memory and Gait

Overview

Journal Alzheimers Dement

Specialties Neurology
Psychiatry

Date 2025 Feb 24

PMID 39988983

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

Affiliations

Soon will be listed here.

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 (Aβ) 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 Aβ 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 Aβ ratio. Dual decline showed greater increases in plasma GFAP and NfL. Dual decline may indicate brain and blood markers underlying dementia.

Citing Articles

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

Tian Q, Greig E, Walker K, Duggan M, Yang Z, Moghekar A Alzheimers Dement. 2025; 21(2):e14612.

PMID: 39988983 PMC: 11848002. DOI: 10.1002/alz.14612.

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