Genetic Risk, Midlife Life's Simple 7, and Incident Dementia in the Atherosclerosis Risk in Communities Study
Abstract
Background and Objectives
Higher scores in Life's Simple 7 (LS7), a metric for cardiovascular and brain health, have been associated with lower risk of dementia. It is uncertain whether this association holds among those with high genetic risk of dementia. Our objective is to evaluate the extent that LS7 may offset dementia risk across the range of genetic risk.
Methods
Participants in the Atherosclerosis Risk in Communities (ARIC) Study were followed from 1987–1989 to 2019. We derived midlife LS7 scores and generated genetic risk scores (GRS) using genome-wide summary statistics of Alzheimer disease, which have been used to study the genetic risk for dementia. Incident dementia was ascertained based on the criteria of the National Institute on Aging–Alzheimer's Association workgroups and Diagnostic and Statistical Manual of Mental Disorders. The associations of the GRS and LS7 with incident dementia were evaluated using Cox regression.
Results
This study included 8,823 European American (EA) and 2,738 African American (AA) participants (mean age at baseline 54 years). We observed 1,603 cases of dementia among EA participants and 631 among AA participants (median follow-up 26.2 years). Higher GRS were associated with higher risk of dementia (EA, hazard ratio [HR] per SD 1.44, 95% CI 1.37, 1.51; AA, HR 1.26, 95% CI 1.16, 1.36). Among EA participants, higher LS7 scores were consistently associated with lower risk of dementia across quintiles of GRS, including the highest quintile (HR per point 0.91, 95% CI 0.87, 0.96). Among AA participants, the associations between LS7 and incident dementia within stratum of GRS had the same direction as among EA participants, although wide CIs and smaller sample sizes limited reliable inferences.
Discussion
Across strata of GRS, higher midlife LS7 scores were associated with lower risk of dementia. Larger sample sizes from diverse populations are needed to obtain more reliable estimates of the effects of modifiable health factors on dementia risk within genetic risk strata in each ancestry group.
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Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.
Publication History
Received: October 21, 2021
Accepted: February 28, 2022
Published online: May 25, 2022
Published in print: July 12, 2022
Disclosure
The authors report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.
Study Funding
The Atherosclerosis Risk in Communities study has been funded in whole or in part with federal funds from the National Heart, Lung, and Blood Institute (NHLBI), NIH, Department of Health and Human Services contract numbers HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I, and HHSN268201700005I (R01HL087641, R01HL059367, and R01HL086694); National Human Genome Research Institute contract U01HG004402; and NIH contract HHSN268200625226C. Neurocognitive data were collected by U01 2U01HL096812, 2U01HL096814, 2U01HL096899, 2U01HL096902, and 2U01HL096917 from the NIH (NHLBI, National Institute of Neurological Disorders and Stroke, National Institute on Aging, and National Institute on Deafness and Other Communication Disorders). Infrastructure was partly supported by grant UL1RR025005, a component of the NIH and NIH Roadmap for Medical Research. This research was supported (in part) by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke (NINDS), NIH.
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