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 Mar 3;8(3):e250096.
doi: 10.1001/jamanetworkopen.2025.0096.

Physical Activity, Alzheimer Plasma Biomarkers, and Cognition

Seung Ae Kim  1   2 , Daeun Shin  3 , Hongki Ham  3   4   5   6 , Yeshin Kim  7 , Yuna Gu  3   8 , Hee Jin Kim  3   4   8   5 , Duk L Na  3   9 , Henrik Zetterberg  10   11   12   13   14   15 , Kaj Blennow  10   11   16   17 , Sang Won Seo  3   4   8   5   6 , Hyemin Jang  1   2 ; Precision Medicine Platform for Mild Cognitive Impairment Based on Multi-omics, Imaging, Evidence-Based R&BD (PREMIER) Consortium
Collaborators, Affiliations

Physical Activity, Alzheimer Plasma Biomarkers, and Cognition

Seung Ae Kim et al. JAMA Netw Open. .

Abstract

Importance: Physical activity (PA) is a nonpharmacological intervention for dementia prevention. The association between PA and Alzheimer disease (AD) plasma biomarkers remains underexplored.

Objective: To investigate the associations among PA; plasma biomarkers, including β-amyloid 42/40 (Aβ42/40), phosphorylated-tau217 (ptau217), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL); and cognition.

Design, setting, and participants: This cross-sectional study included participants with and without cognitive impairment recruited from multiple memory clinics in South Korea between May 2019 and May 2022. Data were analyzed from June to December 2024.

Exposures: PA was assessed as metabolic equivalent task minutes per week using the International Physical Activity Questionnaire and categorized into quartiles from the lowest (Q1) to the highest (Q4).

Main outcomes and measures: Plasma Aβ42/40, ptau217, GFAP, and NfL were measured. Cognition was assessed using the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating-Sum of Boxes (CDR-SB).

Results: Among 1144 participants (mean [SD] age 70.9 [8.7] years; 744 [65.0%] female), the highest PA quartile showed significantly lower ptau217 (estimate [SE], -0.14 [0.06]; P = .01) and NfL (estimate [SE], -0.12 [0.05]; P = .01) compared with the lowest quartile. Higher PA quartiles were associated with higher MMSE scores (estimate [SE]: Q2, 0.93 [0.31]; P = .003; Q3, 0.82 [0.32]; P = .009; Q4, 0.94 [0.32]; P = .004) and lower CDR-SB scores (estimate [SE]: Q2, -0.33 [0.16]; P = .04; Q3, -0.37 [0.16]; P = .02; Q4, -0.55 [0.16]; P = .001) after adjusting for age, sex, education years, and β-amyloid uptake. In subgroup analyses according to age and cognitive status, the associations of PA and plasma biomarkers with cognition were more pronounced in the older (age ≥65 years) and cognitively impaired groups compared with the younger and cognitively unimpaired groups.

Conclusions and relevance: These findings suggest that PA may help delay cognitive decline by modulating neurodegeneration and AD-specific tau pathologies. However, the cross-sectional design limits causal inference, and longitudinal studies are needed to confirm and clarify these associations.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Zetterberg reported receiving personal fees from AbbVie, Acumen, Alector, Alzecure, Alzinova, ALZpath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, BioArctic, Biogen, Cellectricon, Cognito Therapeutics, CogRx, Denali, Eisai, Fujirebio, LabCorp, Lilly, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Quanterix, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, Wave, and WebMD and serving as cofounder and owning stock in Brain Biomarker Solutions in Gothenburg AB outside the submitted work. Dr Blennow reported serving as a consultant or on advisory boards for AbbVie, AC Immune, ALZPath, AriBio, Beckman-Coulter, BioArctic, Biogen, Eisai, Lilly, Moleac Pte Ltd, Neurimmune, Novartis, Ono Pharma, Prothena, Quanterix, Roche Diagnostics, Sanofi, and Siemens Healthineers; serving on data monitoring committees for Julius Clinical and Novartis; receiving personal fees from AC Immune, Biogen, Celdara Medical, Eisai, and Roche Diagnostics; and serving as a co-founder of Brain Biomarker Solutions in Gothenburg AB outside the work presented in this paper. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flowchart of Study Participants
Figure 2.
Figure 2.. Mediation Analysis of Physical Activity and Cognitive Outcomes
Mediation analysis illustrating the association of the highest quartile (vs the lowest quartile) of physical activity with plasma biomarkers and cognitive outcomes as measured by Mini-Mental State Examination (MMSE) and Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores. Solid lines indicate significant associations (P < .05); dashed lines, no significant association (P ≥ .05). Direct and indirect effects are presented as coefficients with 95% CIs with P values. GFAP indicates glial fibrillary acidic protein; NfL, neurofilament light chain; and ptau, phosphorylated tau.
See this image and copyright information in PMC

References

    1. Brickman AM, Manly JJ, Honig LS, et al. . Plasma p-tau181, p-tau217, and other blood-based Alzheimer’s disease biomarkers in a multi-ethnic, community study. Alzheimers Dement. 2021;17(8):1353-1364. doi:10.1002/alz.12301 - DOI - PMC - PubMed
    1. Livingston G, Huntley J, Liu KY, et al. . Dementia prevention, intervention, and care: 2024 report of the Lancet Standing Commission. Lancet. 2024;404(10452):572-628. doi:10.1016/S0140-6736(24)01296-0 - DOI - PubMed
    1. Spires-Jones TL, Hyman BT. The intersection of amyloid beta and tau at synapses in Alzheimer’s disease. Neuron. 2014;82(4):756-771. doi:10.1016/j.neuron.2014.05.004 - DOI - PMC - PubMed
    1. Busche MA, Hyman BT. Synergy between amyloid-β and tau in Alzheimer’s disease. Nat Neurosci. 2020;23(10):1183-1193. doi:10.1038/s41593-020-0687-6 - DOI - PMC - PubMed
    1. van Dyck CH, Swanson CJ, Aisen P, et al. . Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388(1):9-21. doi:10.1056/NEJMoa2212948 - DOI - PubMed

Publication types