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Effects of Aerobic Exercise Training on Systemic Biomarkers and Cognition in Late Middle-Aged Adults at Risk for Alzheimer's Disease
Gaitán JM, Moon HY, Stremlau M, Dubal DB, Cook DB, Okonkwo OC, van Praag H.. Frontiers in endocrinology, 2021-05-20
Topic: Amyloid, tau and blood-test diagnosis
Increasing evidence indicates that physical activity and exercise training may delay or prevent the onset of Alzheimer's disease (AD). However, systemic biomarkers that can measure exercise effects on brain function and that link to relevant metabolic responses are lacking. To begin to address this issue, we utilized blood samples of 23 asymptomatic late middle-aged adults, with familial and genetic risk for AD (mean age 65 years old, 50% female) who underwent 26 weeks of supervised treadmill training. Systemic biomarkers implicated in learning and memory, including the myokine Cathepsin B (CTSB), brain-derived neurotrophic factor (BDNF), and klotho, as well as metabolomics were evaluated. Here we show that aerobic exercise training increases plasma CTSB and that changes in CTSB, but not BDNF or klotho, correlate with cognitive performance. BDNF levels decreased with exercise training. Klotho levels were unchanged by training, but closely associated with change in VO 2 peak. Metabolomic analysis revealed increased levels of polyunsaturated free fatty acids (PUFAs), reductions in ceramides, sphingo- and phospholipids, as well as changes in gut microbiome metabolites and redox homeostasis, with exercise. Multiple metabolites (~30%) correlated with changes in BDNF, but not CSTB or klotho. The positive association between CTSB and cognition, and the modulation of lipid metabolites implicated in dementia, support the beneficial effects of exercise training on brain function. Overall, our analyses indicate metabolic regulation of exercise-induced plasma BDNF changes and provide evidence that CTSB is a marker of cognitive changes in late middle-aged adults at risk for dementia.
Key findings
- Increasing evidence indicates that physical activity and exercise training may delay or prevent the onset of Alzheimer's disease (AD).
- Klotho levels were unchanged by training, but closely associated with change in VO 2 peak.
- Metabolomic analysis revealed increased levels of polyunsaturated free fatty acids (PUFAs), reductions in ceramides, sphingo- and phospholipids, as well as changes in gut microbiome metabolites and redox homeostasis, with exercise.
- Overall, our analyses indicate metabolic regulation of exercise-induced plasma BDNF changes and provide evidence that CTSB is a marker of cognitive changes in late middle-aged adults at risk for dementia.
Why it matters
In 23 asymptomatic late middle-aged adults at risk for Alzheimer's disease, 26 weeks of aerobic exercise training increased plasma Cathepsin B, and changes in Cathepsin B correlated with cognitive performance. BDNF levels decreased with training, and klotho levels were unchanged but closely associated with change in VO2 peak.
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Study details
- Evidence strengthLow
How this study scored 66/100
Published in a peer-reviewed journal, and it is a randomised controlled trial. Scored zero for sample size and effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in endocrinology) |
| Journal's citation record | 2 / 4 | Frontiers in Endocrinology: journal h-index 198 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| 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 (pubmed indexes it as a clinical or observational study) |
| Randomised / blinded | 1 / 2 | Randomised (as stated in the record) |
| Times cited | 5 / 7 | Cited 154 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 22.0 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 4 / 6 | Cited 14.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 3 / 4 | Cited 98 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Henriette van Praag: h-index 57 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, San Francisco: institution h-index 1,915 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34093436) |
| Free to read | 2 / 2 | Free to read |
| Total | 66 / 100 | — |
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Read the original
- DOI: 10.3389/fendo.2021.660181
- PubMed: 34093436
- Original source →
- Free full text: Frontiers in Endocrinology →
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 names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Gaitán, J. M., Moon, H. Y., Stremlau, M., Dubal, D. B., Cook, D. B., Okonkwo, O. C., et al. (2021). Effects of Aerobic Exercise Training on Systemic Biomarkers and Cognition in Late Middle-Aged Adults at Risk for Alzheimer's Disease. Frontiers in endocrinology. https://doi.org/10.3389/fendo.2021.660181
Vancouver
Gaitán JM, Moon HY, Stremlau M, Dubal DB, Cook DB, Okonkwo OC, et al. Effects of Aerobic Exercise Training on Systemic Biomarkers and Cognition in Late Middle-Aged Adults at Risk for Alzheimer's Disease. Frontiers in endocrinology. 2021. doi:10.3389/fendo.2021.660181. PMID: 34093436.
BibTeX
@article{gaitan2021-34093436,
author = {Gaitán, J. M. and Moon, H. Y. and Stremlau, M. and Dubal, D. B. and Cook, D. B. and Okonkwo, O. C. and van Praag, H.},
title = {{Effects of Aerobic Exercise Training on Systemic Biomarkers and Cognition in Late Middle-Aged Adults at Risk for Alzheimer's Disease}},
journal = {Frontiers in endocrinology},
year = {2021},
doi = {10.3389/fendo.2021.660181},
pmid = {34093436},
url = {https://doi.org/10.3389/fendo.2021.660181}
}
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