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Frailty, lifestyle, genetics and dementia risk
Ward DD, Ranson JM, Wallace LMK, Llewellyn DJ, Rockwood K.. Journal of neurology, neurosurgery, and psychiatry, 2021-12-21
Topic: Risk, prevention and care in population studies
Objective To optimise dementia prevention strategies, we must understand the complex relationships between lifestyle behaviours, frailty and genetics. Methods We explored relationships between frailty index, healthy lifestyle and polygenic risk scores (all assessed at study entry) and incident all-cause dementia as recorded on hospital admission records and death register data. Results The analytical sample had a mean age of 64.1 years at baseline (SD=2.9) and 53% were women. Incident dementia was detected in 1762 participants (median follow-up time=8.0 years). High frailty was associated with increased dementia risk independently of genetic risk (HR 3.68, 95% CI 3.11 to 4.35). Frailty mediated 44% of the relationship between healthy lifestyle behaviours and dementia risk (indirect effect HR 0.95, 95% CI 0.95 to 0.96). Participants at high genetic risk and with high frailty had 5.8 times greater risk of incident dementia compared with those at low genetic risk and with low frailty (HR 5.81, 95% CI 4.01 to 8.42). Higher genetic risk was most influential in those with low frailty (HR 1.31, 95% CI 1.22 to 1.40) but not influential in those with high frailty (HR 1.09, 95% CI 0.92 to 1.28). Conclusion Frailty is strongly associated with dementia risk and affects the risk attributable to genetic factors. Frailty should be considered an important modifiable risk factor for dementia and a target for dementia prevention strategies, even among people at high genetic risk.
Key findings
- Results The analytical sample had a mean age of 64.1 years at baseline (SD=2.9) and 53% were women.
- High frailty was associated with increased dementia risk independently of genetic risk (HR 3.68, 95% CI 3.11 to 4.35).
- Participants at high genetic risk and with high frailty had 5.8 times greater risk of incident dementia compared with those at low genetic risk and with low frailty (HR 5.81, 95% CI 4.01 to 8.42).
- Conclusion Frailty is strongly associated with dementia risk and affects the risk attributable to genetic factors.
Why it matters
High frailty was linked to a higher risk of dementia, independent of genetic risk, and frailty mediated part of the relationship between healthy lifestyle behaviours and dementia risk. Frailty should be considered an important modifiable risk factor for dementia.
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Study details
- Participants1,762
- Effect sizeHR 3.68; HR 0.95; HR 5.81
- Evidence strengthLow
How this study scored 63/100
Published in a peer-reviewed journal. Scored zero for study design and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neurology, neurosurgery, and psychiatry) |
| Journal's citation record | 3 / 4 | Journal of Neurology Neurosurgery & Psychiatry: journal h-index 336 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| 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 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,762 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 168 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 28.0 citations a year over 6 year(s) since 2022 |
| 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 | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 3 / 4 | Cited 139 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Kenneth J. Rockwood: h-index 135 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34933996) |
| Free to read | 2 / 2 | Free to read |
| Total | 63 / 100 | — |
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Read the original
- DOI: 10.1136/jnnp-2021-327396
- PubMed: 34933996
- Original source →
- Free full text: Journal of Neurology Neurosurgery & Psychiatry →
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. Check the citation against the original before you use it.
APA 7th
Ward, D. D., Ranson, J. M., Wallace, L. M. K., Llewellyn, D. J., & Rockwood, K. (2022). Frailty, lifestyle, genetics and dementia risk. Journal of neurology, neurosurgery, and psychiatry. https://doi.org/10.1136/jnnp-2021-327396
Vancouver
Ward DD, Ranson JM, Wallace LMK, Llewellyn DJ, Rockwood K. Frailty, lifestyle, genetics and dementia risk. Journal of neurology, neurosurgery, and psychiatry. 2022. doi:10.1136/jnnp-2021-327396. PMID: 34933996.
BibTeX
@article{ward2022-34933996,
author = {Ward, D. D. and Ranson, J. M. and Wallace, L. M. K. and Llewellyn, D. J. and Rockwood, K.},
title = {{Frailty, lifestyle, genetics and dementia risk}},
journal = {Journal of neurology, neurosurgery, and psychiatry},
year = {2022},
doi = {10.1136/jnnp-2021-327396},
pmid = {34933996},
url = {https://doi.org/10.1136/jnnp-2021-327396}
}
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