1. Cardiometabolic multimorbidity, genetic risk, and dementia: a prospective cohort study
- Author
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Tai, XY, Veldsman, M, Lyall, DM, Littlejohns, TJ, Langa, KM, Husain, M, Ranson, J, and Llewellyn, DJ
- Subjects
Psychiatry and Mental health ,Health (social science) ,Risk Factors ,Diabetes Mellitus ,Humans ,Multimorbidity ,Dementia ,Prospective Studies ,Geriatrics and Gerontology ,Family Practice ,United States - Abstract
Background Individual cardiometabolic disorders and genetic factors are associated with an increased dementia risk; however, the relationship between dementia and cardiometabolic multimorbidity is unclear. We investigated whether cardiometabolic multimorbidity increases the risk of dementia, regardless of genetic risk, and examined for associated brain structural changes. Methods We examined health and genetic data from 203 038 UK Biobank participants of European ancestry, aged 60 years or older without dementia at baseline assessment (2006–10) and followed up until March 31, 2021, in England and Scotland and Feb 28, 2018, in Wales, as well as brain structural data in a nested imaging subsample of 12 236 participants. A cardiometabolic multimorbidity index comprising stroke, diabetes, and myocardial infarction (one point for each), and a polygenic risk score for dementia (with low, intermediate, and high risk groups) were calculated for each participant. The main outcome measures were incident all-cause dementia and brain structural metrics. Findings The dementia risk associated with high cardiometabolic multimorbidity was three times greater than that associated with high genetic risk (hazard ratio [HR] 5·55, 95% CI 3·39–9·08, p2, 12 110 = 10·70; p2, 12 236 = 55·65; p Interpretation Cardiometabolic multimorbidity was independently associated with the risk of dementia and extensive brain imaging differences to a greater extent than was genetic risk. Targeting cardiometabolic multimorbidity might help to reduce the risk of dementia, regardless of genetic risk. Funding Wellcome Trust, Alzheimer's Research UK, Alan Turing Institute/Engineering and Physical Sciences Research Council, the National Institute for Health Research Applied Research Collaboration South West Peninsula, National Health and Medical Research Council, JP Moulton Foundation, and National Institute on Aging/National Institutes of Health.
- Published
- 2022