Frailty, lifestyle, genetics and dementia risk
ObjectiveTo optimise dementia prevention strategies, we must understand the complex relationships between lifestyle behaviours, frailty and genetics.MethodsWe explored relationships between frailty index, healthy lifestyle and polygenic risk scores (all assessed at study entry) and incident all-caus...
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Published in | Journal of neurology, neurosurgery and psychiatry Vol. 93; no. 4; pp. 343 - 350 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
England
BMJ Publishing Group Ltd
01.04.2022
BMJ Publishing Group LTD BMJ Publishing Group |
Series | Original research |
Subjects | |
Online Access | Get full text |
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Summary: | ObjectiveTo optimise dementia prevention strategies, we must understand the complex relationships between lifestyle behaviours, frailty and genetics.MethodsWe 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.ResultsThe 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).ConclusionFrailty 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. |
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Bibliography: | Original research ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 DJL and KR are joint senior authors. |
ISSN: | 0022-3050 1468-330X 1468-330X |
DOI: | 10.1136/jnnp-2021-327396 |