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Physical activity attenuates age-related biomarker alterations in preclinical AD
Okonkwo OC, Schultz SA, Oh JM, Larson J, Edwards D, Cook D, Koscik R, Gallagher CL et al.. Neurology, 2014-10-08
Topic: Amyloid, tau and blood-test diagnosis
Objective To examine whether engagement in physical activity might favorably alter the age-dependent evolution of Alzheimer disease (AD)-related brain and cognitive changes in a cohort of at-risk, late-middle-aged adults. Methods Three hundred seventeen enrollees in the Wisconsin Registry for Alzheimer's Prevention underwent T1 MRI; a subset also underwent (11)C-Pittsburgh compound B-PET (n = 186) and (18)F-fluorodeoxyglucose-PET (n = 152) imaging. Participants' responses on a self-report measure of current physical activity were used to classify them as either physically active or physically inactive based on American Heart Association guidelines. They also completed a comprehensive neuropsychological battery. Covariate-adjusted regression analyses were used to test whether the adverse effect of age on imaging and cognitive biomarkers was modified by physical activity. Results There were significant age × physical activity interactions for β-amyloid burden (p = 0.014), glucose metabolism (p = 0.015), and hippocampal volume (p = 0.025) such that, with advancing age, physically active individuals exhibited a lesser degree of biomarker alterations compared with the physically inactive. Similar age × physical activity interactions were also observed on cognitive domains of Immediate Memory (p = 0.042) and Visuospatial Ability (p = 0.016). In addition, the physically active group had higher scores on Speed and Flexibility (p = 0.002) compared with the inactive group. Conclusions In a middle-aged, at-risk cohort, a physically active lifestyle is associated with an attenuation of the deleterious influence of age on key biomarkers of AD pathophysiology. However, because our observational, cross-sectional design cannot establish causality, randomized controlled trials/longitudinal studies will be necessary for determining whether midlife participation in structured physical exercise forestalls the development of AD and related disorders in later life.
Key findings
- Results There were significant age × physical activity interactions for β-amyloid burden (p = 0.014), glucose metabolism (p = 0.015), and hippocampal volume (p = 0.025) such that, with advancing age, physically active individuals exhibited a lesser degree of biomarker alterations compared with the physically inactive.
- In addition, the physically active group had higher scores on Speed and Flexibility (p = 0.002) compared with the inactive group.
- Conclusions In a middle-aged, at-risk cohort, a physically active lifestyle is associated with an attenuation of the deleterious influence of age on key biomarkers of AD pathophysiology.
Why it matters
In this middle-aged, at-risk cohort, people who reported being physically active showed less age-related change in amyloid burden, glucose metabolism, hippocampal volume, and some cognitive measures than inactive people. The study was cross-sectional, so it cannot show that physical activity causes these differences or prevents Alzheimer's disease.
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Study details
- Study designcross-sectional
- Participants186
- Evidence strengthHigh
How this study scored 60/100
Published in a leading specialty journal, and it is a snapshot of people at one point in time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2014 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 186 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 228 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 16.3 citations a year over 14 year(s) since 2014 |
| Impact for its field and year | 4 / 6 | Cited 13.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 13 other studies in this library |
| Still being cited | 2 / 4 | Cited 31 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Mark A. Sager: h-index 70 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | William S. Middleton Memorial Veterans Hospital: institution h-index 289 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25298312) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 60 / 100 | — |
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Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Okonkwo, O. C., Schultz, S. A., Oh, J. M., Larson, J., Edwards, D., Cook, D., et al. (2014). Physical activity attenuates age-related biomarker alterations in preclinical AD. Neurology. https://doi.org/10.1212/wnl.0000000000000964
Vancouver
Okonkwo OC, Schultz SA, Oh JM, Larson J, Edwards D, Cook D, et al. Physical activity attenuates age-related biomarker alterations in preclinical AD. Neurology. 2014. doi:10.1212/wnl.0000000000000964. PMID: 25298312.
BibTeX
@article{okonkwo2014-25298312,
author = {Okonkwo, O. C. and Schultz, S. A. and Oh, J. M. and Larson, J. and Edwards, D. and Cook, D. and Koscik, R. and Gallagher, C. L. and others},
title = {{Physical activity attenuates age-related biomarker alterations in preclinical AD}},
journal = {Neurology},
year = {2014},
doi = {10.1212/wnl.0000000000000964},
pmid = {25298312},
url = {https://doi.org/10.1212/wnl.0000000000000964}
}
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