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Sleep, 24-Hour Activity Rhythms, and Subsequent Amyloid-β Pathology
Nguyen Ho PT, Hoepel SJW, Rodriguez-Ayllon M, Luik AI, Vernooij MW, Neitzel J.. JAMA neurology, 2024-08-01
Topic: Amyloid, tau and blood-test diagnosis
Importance Sleep disturbances are common among older adults and have been associated with the development of Alzheimer disease (AD), such as amyloid-β (Aβ) pathology. Results The mean (range) age in the study population was 61.5 (48-80) years at baseline and 69.2 (60-88) years at follow-up; 150 (47%) were women. Higher intradaily variability at baseline, an indicator of fragmented 24-hour activity rhythms, was associated with higher Aβ PET burden at follow-up (β, 0.15; bootstrapped 95% CI, 0.04 to 0.26; bootstrapped P = .02, false discovery rate [FDR] P = .048). APOE genotype modified this association, which was stronger in APOE4 carriers (β, 0.38; bootstrapped 95% CI, 0.05 to 0.64; bootstrapped P = .03) compared to noncarriers (β, 0.07; bootstrapped 95% CI, -0.04 to 0.18; bootstrapped P = .19). The findings remained largely similar after excluding participants with AD pathology at baseline, suggesting that a fragmented 24-hour activity rhythm may have preceded Aβ deposition. No other objective or self-reported measure of sleep was associated with Aβ. Conclusions and relevance Among community-dwelling adults included in this study, higher fragmentation of the 24-hour activity rhythms was associated with greater subsequent Aβ burden, especially in APOE4 carriers. These results suggest that rest-activity fragmentation could represent a modifiable risk factor for AD.
Key findings
- Importance Sleep disturbances are common among older adults and have been associated with the development of Alzheimer disease (AD), such as amyloid-β (Aβ) pathology.
- Results The mean (range) age in the study population was 61.5 (48-80) years at baseline and 69.2 (60-88) years at follow-up; 150 (47%) were women.
- Higher intradaily variability at baseline, an indicator of fragmented 24-hour activity rhythms, was associated with higher Aβ PET burden at follow-up (β, 0.15; bootstrapped 95% CI, 0.04 to 0.26; bootstrapped P = .02, false discovery rate [FDR] P = .048).
- APOE genotype modified this association, which was stronger in APOE4 carriers (β, 0.38; bootstrapped 95% CI, 0.05 to 0.64; bootstrapped P = .03) compared to noncarriers (β, 0.07; bootstrapped 95% CI, -0.04 to 0.18; bootstrapped P = .19).
- The findings remained largely similar after excluding participants with AD pathology at baseline, suggesting that a fragmented 24-hour activity rhythm may have preceded Aβ deposition.
Why it matters
In community-dwelling older adults, more fragmented 24-hour activity rhythms at baseline were associated with greater amyloid burden at follow-up, especially in APOE4 carriers, while no other sleep measure was associated with amyloid. This suggests that rest-activity fragmentation could be a modifiable risk factor for Alzheimer's disease, though the study is observational and cannot prove cause and effect.
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Study details
- Study designcohort study
- Participants639
- Evidence strengthModerate
How this study scored 67/100
Published in a leading specialty journal, and it is a cohort study following people over 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 (JAMA neurology) |
| Journal's citation record | 2 / 4 | JAMA Neurology: journal h-index 235 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 639 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 | 4 / 7 | Cited 56 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 14.0 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 4 / 6 | Cited 15.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 3 / 4 | Cited 56 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Julia Neitzel: h-index 22 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 38913396) |
| Free to read | 2 / 2 | Free to read |
| Total | 67 / 100 | — |
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Read the original
- DOI: 10.1001/jamaneurol.2024.1755
- PubMed: 38913396
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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. Check the citation against the original before you use it.
APA 7th
Nguyen Ho, P. T., Hoepel, S. J. W., Rodriguez-Ayllon, M., Luik, A. I., Vernooij, M. W., & Neitzel, J. (2024). Sleep, 24-Hour Activity Rhythms, and Subsequent Amyloid-β Pathology. JAMA neurology. https://doi.org/10.1001/jamaneurol.2024.1755
Vancouver
Nguyen Ho PT, Hoepel SJW, Rodriguez-Ayllon M, Luik AI, Vernooij MW, Neitzel J. Sleep, 24-Hour Activity Rhythms, and Subsequent Amyloid-β Pathology. JAMA neurology. 2024. doi:10.1001/jamaneurol.2024.1755. PMID: 38913396.
BibTeX
@article{nguyenho2024-38913396,
author = {Nguyen Ho, P. T. and Hoepel, S. J. W. and Rodriguez-Ayllon, M. and Luik, A. I. and Vernooij, M. W. and Neitzel, J.},
title = {{Sleep, 24-Hour Activity Rhythms, and Subsequent Amyloid-β Pathology}},
journal = {JAMA neurology},
year = {2024},
doi = {10.1001/jamaneurol.2024.1755},
pmid = {38913396},
url = {https://doi.org/10.1001/jamaneurol.2024.1755}
}
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