Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 10;80(7):glaf110.
doi: 10.1093/gerona/glaf110.

Relationship of Alzheimer's Disease and Related Dementias Plasma Biomarkers With Mobility in Cognitively Unimpaired Older Adults

Atalie C Thompson  1   2 , Xiaoyan Leng  3 , Michael E Miller  4 , Thomas C Register  5 , Paul J Laurienti  6 , Michelle M Mielke  2   7 , Suzanne Craft  2 , Stephen B Kritchevsky  2
Affiliations

Relationship of Alzheimer's Disease and Related Dementias Plasma Biomarkers With Mobility in Cognitively Unimpaired Older Adults

Atalie C Thompson et al. J Gerontol A Biol Sci Med Sci. .

Abstract

Background: Temporal relationships between physical and cognitive decline with aging are poorly understood, and little is known about the underlying mechanisms linking these conditions. We hypothesized that plasma biomarkers of Alzheimer's disease and related dementias may be associated with mobility performance in older adults who are cognitively unimpaired.

Methods: We constructed separate linear mixed models to examine the cross-sectional associations of 5 plasma Alzheimer's disease and related dementias and aging-related biomarkers with 4 measures of mobility in a cohort of 192 cognitively unimpaired older adults. We secondarily described the association of the same biomarkers with 4 cognitive domain scores.

Results: Higher phorphorylated-tau181 was associated with worse performance on the expanded short physical performance battery, slower 4 m gait speed, and shorter balance time. Higher neurofilament light was associated with worse expanded short physical performance battery, slower 4 m gait speed, and slower 400 m gait speed in adjusted models. However, there was no association of Aβ42/Aβ40, p-tau217, or glial fibrillary acidic protein with mobility. Only p-tau217 was associated with global and processing speed cognitive domain scores in multivariable models, but not after adjusting for multiple comparisons.

Conclusions: These data suggest that p-tau181 and neurofilament light are potential markers of mobility performance in cognitively normal older adults, even when they are not associated with cognitive performance. Future studies should examine how such markers predict change over time in mobility and cognitive function and whether they may indicate pathways that could be targeted for preventive management.

Keywords: Alzheimer’s disease; Functional performance; Gait.

PubMed Disclaimer

Conflict of interest statement

Dr. Mielke has served on scientific advisory boards and/or has consulted for Acadia, Biogen, Eisai, Lilly, Merck, Novo Nordisk, and Roche. The other authors have no relevant conflicts of interest to disclose.

Figures

Figure 1.
Figure 1.
Correlations of plasma biomarkers and physical performance measures. Heatmap of Spearman’s correlation between plasma biomarkers and physical performance measures. The correlation coefficient magnitude is shown in the calibration bar, and all values are adjusted for plate. Unadjusted correlations (p < .05) are bolded. Adjusted p values < .05 (Benajmini–Hochberg FDR < 0.05) are labeled by *.
Figure 2.
Figure 2.
Heatmap of standardized beta coefficients of the association of plasma biomarkers with physical performance measures. Heatmap of standardized beta coefficients from unadjusted Model 1 and fully adjusted Model 2 for plasma biomarkers with measures of physical performance. All models are adjusted for plate. The shades of the heat map represent the p values as shown in the calibration bar. Significant unadjusted correlations (p < .05) are bolded. Adjusted p values < .05 (Benjamini–Hochberg FDR < 0.05) are labeled by *.
See this image and copyright information in PMC

References

    1. Deshpande N, Metter EJ, Bandinelli S, Guralnik J, Ferrucci L.. Gait speed under varied challenges and cognitive decline in older persons: a prospective study. Age Ageing. 2009;38(5):509–514. https://doi.org/ 10.1093/ageing/afp093 - DOI - PMC - PubMed
    1. Fitzpatrick AL, Buchanan CK, Nahin RL, et al. ; Ginkgo Evaluation of Memory (GEM) Study Investigators. Associations of gait speed and other measures of physical function with cognition in a healthy cohort of elderly persons. J Gerontol A Biol Sci Med Sci. 2007;62(11):1244–1251. https://doi.org/ 10.1093/gerona/62.11.1244 - DOI - PubMed
    1. Wilkins CH, Roe CM, Morris JC, Galvin JE.. Mild physical impairment predicts future diagnosis of dementia of the Alzheimer’s type. J Am Geriatr Soc. 2013;61(7):1055–1059. https://doi.org/ 10.1111/jgs.12255 - DOI - PMC - PubMed
    1. Buracchio T, Dodge HH, Howieson D, Wasserman D, Kaye J.. The trajectory of gait speed preceding mild cognitive impairment. Arch Neurol. 2010;67(8):980–986. https://doi.org/ 10.1001/archneurol.2010.159 - DOI - PMC - PubMed
    1. Tuena C, Pupillo C, Stramba-Badiale C, Stramba-Badiale M, Riva G.. Predictive power of gait and gait-related cognitive measures in amnestic mild cognitive impairment: a machine learning analysis. Front Hum Neurosci. 2023;17:1328713. https://doi.org/ 10.3389/fnhum.2023.1328713 - DOI - PMC - PubMed