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Comment
. 2025 Jul 1;82(7):644-654.
doi: 10.1001/jamaneurol.2025.1495.

Contribution of Modifiable Midlife and Late-Life Vascular Risk Factors to Incident Dementia

Jason R Smith  1 , James Russell Pike  2 , Rebecca F Gottesman  3 , David S Knopman  4 , Pamela L Lutsey  5 , Priya Palta  6 , B Gwen Windham  7 , Elizabeth Selvin  1   8 , Moyses Szklo  1 , Karen J Bandeen-Roche  9 , Josef Coresh  2   10 , A Richey Sharrett  1 , Alden L Gross  1   11 , Jennifer A Deal  1
Affiliations
Comment

Contribution of Modifiable Midlife and Late-Life Vascular Risk Factors to Incident Dementia

Jason R Smith et al. JAMA Neurol. .

Abstract

Importance: Midlife vascular risk factors are associated with an elevated risk of dementia. However, the total contribution of vascular risk factors in midlife and late life with incident dementia is uncertain.

Objective: To quantify the proportion of incident dementia attributable to modifiable vascular risk factors measured in midlife and late life and to examine differences by apolipoprotein ε4 genotype, self-reported race, and sex.

Design, setting, and participants: This was a prospective cohort analysis of the Atherosclerosis Risk in Communities (ARIC) study using 33 years of follow-up (1987-2020). The setting included ARIC field centers (Jackson, Mississippi; Forsyth County, North Carolina; Minneapolis suburbs, Minnesota; Washington County, Maryland). Study baseline in Black and White participants with complete exposure and covariate data was set by age at risk factor measurement (45-54 years, 55-64 years, and 65-74 years). Data were analyzed from August 2023 to December 2024.

Exposures: Hypertension (systolic blood pressure [BP] ≥130 mm Hg, diastolic BP ≥80 mm Hg, or use of medication for BP), diabetes (fasting glucose ≥126 mg/dL, nonfasting glucose ≥200 mg/dL, self-reported physician's diagnosis, or use of any diabetes medication), and current smoking (self-reported).

Main outcomes and measures: Incident dementia. Population attributable fractions were estimated by age 80 years, and separately after 80 years, from having at least 1 vascular risk factor by age at risk factor measurement.

Results: A total of 7731 participants were included in analysis of risk factors measured at age 45 to 54 years (4494 female [58%]; 2207 Black [29%]; 5524 White [71%]), 12 274 contributed to analysis of risk factors measured at age 55 to 64 years (6698 female [55%]; 2886 Black [24%]; 9388 White [76%]), and 6787 contributed to analysis of risk factors measured at age 65 to 74 years (3764 female [56%], 1375 Black [20%]; 5412 White [80%]). There were 801, 995, and 422 dementia cases by 80 years, respectively. The fraction of dementia by 80 years attributable to at least 1 vascular factor at age 45 to 54 years was 21.8% (95% CI, 14.3%-29.3%), at 55 to 64 years was 26.4% (95% CI, 19.1%-33.6%), and at 65 to 74 years was 44.0% (95% CI, 30.9%-57.2%). Attributable fractions for these factors were higher in apolipoprotein ε4 noncarriers at age 55 years and older (range, 33.3%-61.4%), Black individuals at age 45 years and older (range, 25.5%-52.9%), and female individuals at age 55 years and older (range, 29.2%-51.3%). Only 2% to 8% of dementia cases after 80 years were attributable to these factors.

Conclusions and relevance: Results of this cohort study suggest that between 22% and 44% of incident dementia cases by 80 years in the ARIC study were attributed to midlife and late-life vascular risk factors. Assuming causal relationships, maintaining optimal vascular health across the life course could mitigate a sizeable proportion of dementia risk by 80 years.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Smith reported receiving grants from the National Institute on Aging (Epidemiology and Biostatistics of Aging Predoctoral Training grant) and a scholarship from the Cochlear Center for Hearing and Public Health (Cochlear Center Epidemiology Scholarship for Sensory Loss in Aging) outside the submitted work. Dr Knopman reported receiving grants from the Biogen Clinical trial site, the Lilly Clinical trial site, and from Washington University in St Louis as a data safety monitoring board member (DSMB) outside the submitted work; serving on a DSMB for the Dominantly Inherited Alzheimer Network Treatment Unit study; serving on a DSMB for a tau therapeutic for Biogen (until 2021) but received no personal compensation; serving as an investigator in clinical trials sponsored by Biogen, Lilly Pharmaceuticals, and the University of Southern California; serving as a consultant for Roche, Samus Therapeutics, Magellan Health, BioVie, and Alzeca Biosciences but received no personal compensation; attending an Eisai advisory board meeting for lecanemab on December 2, 2022, but received no compensation; and receiving funding from the National Institutes of Health (NIH). Dr Lutsey reported receiving grants from the NIH to her institution during the conduct of the study. Dr Palta reported receiving grants from the NIH during the conduct of the study. Dr Windham reported receiving grants from the NIH during the conduct of the study. Dr Selvin reported receiving grants from the NIH; personal fees from the American Diabetes Association; and serving as deputy editor of Diabetes Care and receiving an honorarium for this work outside the submitted work. Dr Bandeen-Roche reported receiving grants from National Institute on Aging (NIA), the NIH, and Geisinger Health Systems outside the submitted work. Dr Deal reported being the section editor for Frontiers in Epidemiology, Aging and Lifecourse Section, and receiving grants from the NIA Paid to Institution during the conduct of the study. No other disclosures were reported.

Comment on

References

    1. Martin SS, Aday AW, Almarzooq ZI, et al. ; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee . 2024 Heart disease and stroke statistics: a report of US and global data from the American Heart Association. Circulation. 2024;149(8):e347-e913. doi: 10.1161/CIR.0000000000001209 - DOI - PMC - PubMed
    1. Gorelick PB, Scuteri A, Black SE, et al. ; American Heart Association Stroke Council, Council on Epidemiology and Prevention, Council on Cardiovascular Nursing, Council on Cardiovascular Radiology and Intervention, and Council on Cardiovascular Surgery and Anesthesia . Vascular contributions to cognitive impairment and dementia: a statement for health care professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42(9):2672-2713. doi: 10.1161/STR.0b013e3182299496 - DOI - PMC - PubMed
    1. Gorelick PB, Furie KL, Iadecola C, et al. ; American Heart Association/American Stroke Association . Defining optimal brain health in adults: a presidential advisory from the American Heart Association/American Stroke Association. Stroke. 2017;48(10):e284-e303. doi: 10.1161/STR.0000000000000148 - DOI - PMC - PubMed
    1. Hachinski V, Einhäupl K, Ganten D, et al. Preventing dementia by preventing stroke: the Berlin Manifesto. Alzheimers Dement. 2019;15(7):961-984. doi: 10.1016/j.jalz.2019.06.001 - DOI - PMC - PubMed
    1. Livingston G, Huntley J, Liu KY, et al. Dementia prevention, intervention, and care: 2024 report of the Lancet Standing Commission. Lancet. 2024;404(10452):572-628. doi: 10.1016/S0140-6736(24)01296-0 - DOI - PubMed

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