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August 18, 2020; 95 (7) Article

Cardiovascular risk factors and accelerated cognitive decline in midlife

The CARDIA Study

Kristine Yaffe, Amber L. Bahorik, Tina D. Hoang, Sarah Forrester, David R. Jacobs, Cora E. Lewis, Donald M. Lloyd-Jones, Stephen Sidney, Jared P. Reis
First published July 15, 2020, DOI: https://doi.org/10.1212/WNL.0000000000010078
Kristine Yaffe
From the Departments of Psychiatry (K.Y., A.L.B.), Neurology (K.Y.), and Epidemiology (K.Y.), University of California, San Francisco; San Francisco VA Medical Center (K.Y.); Northern California Institute Research for Research and Education (T.D.H.), San Francisco; University of Massachusetts School of Medicine (S.F.), Worchester; School of Public Health (D.R.J.), University of Minnesota, Minneapolis; School of Public Health (C.E.L.), University of Alabama at Birmingham; Northwestern University Feinberg School of Medicine (D.M.L.-J.), Chicago, IL; Division of Research (S.S.), Kaiser Permanente Northern California, Oakland; and National Heart, Lung, and Blood Institute (J.R.), Bethesda, MD.
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Amber L. Bahorik
From the Departments of Psychiatry (K.Y., A.L.B.), Neurology (K.Y.), and Epidemiology (K.Y.), University of California, San Francisco; San Francisco VA Medical Center (K.Y.); Northern California Institute Research for Research and Education (T.D.H.), San Francisco; University of Massachusetts School of Medicine (S.F.), Worchester; School of Public Health (D.R.J.), University of Minnesota, Minneapolis; School of Public Health (C.E.L.), University of Alabama at Birmingham; Northwestern University Feinberg School of Medicine (D.M.L.-J.), Chicago, IL; Division of Research (S.S.), Kaiser Permanente Northern California, Oakland; and National Heart, Lung, and Blood Institute (J.R.), Bethesda, MD.
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Tina D. Hoang
From the Departments of Psychiatry (K.Y., A.L.B.), Neurology (K.Y.), and Epidemiology (K.Y.), University of California, San Francisco; San Francisco VA Medical Center (K.Y.); Northern California Institute Research for Research and Education (T.D.H.), San Francisco; University of Massachusetts School of Medicine (S.F.), Worchester; School of Public Health (D.R.J.), University of Minnesota, Minneapolis; School of Public Health (C.E.L.), University of Alabama at Birmingham; Northwestern University Feinberg School of Medicine (D.M.L.-J.), Chicago, IL; Division of Research (S.S.), Kaiser Permanente Northern California, Oakland; and National Heart, Lung, and Blood Institute (J.R.), Bethesda, MD.
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Sarah Forrester
From the Departments of Psychiatry (K.Y., A.L.B.), Neurology (K.Y.), and Epidemiology (K.Y.), University of California, San Francisco; San Francisco VA Medical Center (K.Y.); Northern California Institute Research for Research and Education (T.D.H.), San Francisco; University of Massachusetts School of Medicine (S.F.), Worchester; School of Public Health (D.R.J.), University of Minnesota, Minneapolis; School of Public Health (C.E.L.), University of Alabama at Birmingham; Northwestern University Feinberg School of Medicine (D.M.L.-J.), Chicago, IL; Division of Research (S.S.), Kaiser Permanente Northern California, Oakland; and National Heart, Lung, and Blood Institute (J.R.), Bethesda, MD.
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David R. Jacobs Jr
From the Departments of Psychiatry (K.Y., A.L.B.), Neurology (K.Y.), and Epidemiology (K.Y.), University of California, San Francisco; San Francisco VA Medical Center (K.Y.); Northern California Institute Research for Research and Education (T.D.H.), San Francisco; University of Massachusetts School of Medicine (S.F.), Worchester; School of Public Health (D.R.J.), University of Minnesota, Minneapolis; School of Public Health (C.E.L.), University of Alabama at Birmingham; Northwestern University Feinberg School of Medicine (D.M.L.-J.), Chicago, IL; Division of Research (S.S.), Kaiser Permanente Northern California, Oakland; and National Heart, Lung, and Blood Institute (J.R.), Bethesda, MD.
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Cora E. Lewis
From the Departments of Psychiatry (K.Y., A.L.B.), Neurology (K.Y.), and Epidemiology (K.Y.), University of California, San Francisco; San Francisco VA Medical Center (K.Y.); Northern California Institute Research for Research and Education (T.D.H.), San Francisco; University of Massachusetts School of Medicine (S.F.), Worchester; School of Public Health (D.R.J.), University of Minnesota, Minneapolis; School of Public Health (C.E.L.), University of Alabama at Birmingham; Northwestern University Feinberg School of Medicine (D.M.L.-J.), Chicago, IL; Division of Research (S.S.), Kaiser Permanente Northern California, Oakland; and National Heart, Lung, and Blood Institute (J.R.), Bethesda, MD.
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Donald M. Lloyd-Jones
From the Departments of Psychiatry (K.Y., A.L.B.), Neurology (K.Y.), and Epidemiology (K.Y.), University of California, San Francisco; San Francisco VA Medical Center (K.Y.); Northern California Institute Research for Research and Education (T.D.H.), San Francisco; University of Massachusetts School of Medicine (S.F.), Worchester; School of Public Health (D.R.J.), University of Minnesota, Minneapolis; School of Public Health (C.E.L.), University of Alabama at Birmingham; Northwestern University Feinberg School of Medicine (D.M.L.-J.), Chicago, IL; Division of Research (S.S.), Kaiser Permanente Northern California, Oakland; and National Heart, Lung, and Blood Institute (J.R.), Bethesda, MD.
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Stephen Sidney
From the Departments of Psychiatry (K.Y., A.L.B.), Neurology (K.Y.), and Epidemiology (K.Y.), University of California, San Francisco; San Francisco VA Medical Center (K.Y.); Northern California Institute Research for Research and Education (T.D.H.), San Francisco; University of Massachusetts School of Medicine (S.F.), Worchester; School of Public Health (D.R.J.), University of Minnesota, Minneapolis; School of Public Health (C.E.L.), University of Alabama at Birmingham; Northwestern University Feinberg School of Medicine (D.M.L.-J.), Chicago, IL; Division of Research (S.S.), Kaiser Permanente Northern California, Oakland; and National Heart, Lung, and Blood Institute (J.R.), Bethesda, MD.
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Jared P. Reis
From the Departments of Psychiatry (K.Y., A.L.B.), Neurology (K.Y.), and Epidemiology (K.Y.), University of California, San Francisco; San Francisco VA Medical Center (K.Y.); Northern California Institute Research for Research and Education (T.D.H.), San Francisco; University of Massachusetts School of Medicine (S.F.), Worchester; School of Public Health (D.R.J.), University of Minnesota, Minneapolis; School of Public Health (C.E.L.), University of Alabama at Birmingham; Northwestern University Feinberg School of Medicine (D.M.L.-J.), Chicago, IL; Division of Research (S.S.), Kaiser Permanente Northern California, Oakland; and National Heart, Lung, and Blood Institute (J.R.), Bethesda, MD.
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Citation
Cardiovascular risk factors and accelerated cognitive decline in midlife
The CARDIA Study
Kristine Yaffe, Amber L. Bahorik, Tina D. Hoang, Sarah Forrester, David R. Jacobs, Cora E. Lewis, Donald M. Lloyd-Jones, Stephen Sidney, Jared P. Reis
Neurology Aug 2020, 95 (7) e839-e846; DOI: 10.1212/WNL.0000000000010078

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Abstract

Objective Increasing evidence supports an association between midlife cardiovascular risk factors (CVRFs) and risk of dementia, but less is known about whether CVRFs influence cognition in midlife. We examined the relationship between CVRFs and midlife cognitive decline.

Methods In 2,675 black and white middle-aged adults (mean age 50.2 ± 3.6 years, 57% female, 45% black), we measured CVRFs at baseline: hypertension (31%), diabetes mellitus (11%), obesity (43%), high cholesterol (9%), and current cigarette smoking (15%). We administered cognitive tests of memory, executive function, and processing speed at baseline and 5 years later. Using logistic regression, we estimated the association of CVRFs with accelerated cognitive decline (race-specific decline ≥1.5 SD from the mean change) on a composite cognitive score.

Results Five percent (n = 143) of participants had accelerated cognitive decline over 5 years. Smoking, hypertension, and diabetes mellitus were associated with an increased likelihood of accelerated decline after multivariable adjustment (adjusted odds ratio [AOR] 1.65, 95% confidence interval [CI] 1.00–2.71; AOR 1.87, 95% CI 1.26–2.75; AOR 2.45, 95% CI 1.54–3.88, respectively), while obesity and high cholesterol were not associated with risk of decline. These results were similar when stratified by race. The likelihood of accelerated decline also increased with greater number of CVRFs (1–2 CVRFs: AOR 1.77, 95% CI 1.02–3.05; ≥3 CVRFs: AOR 2.94, 95% CI 1.64–5.28) and with Framingham Coronary Heart Disease Risk Score ≥10 (AOR 2.29, 95% CI 1.21–4.34).

Conclusions Midlife CVRFs, especially hypertension, diabetes mellitus, and smoking, are common and associated with accelerated cognitive decline at midlife. These results identify potential modifiable targets to prevent midlife cognitive decline and highlight the need for a life course approach to cognitive function and aging.

Glossary

AOR=
adjusted OR;
ARIC=
Atherosclerosis Risk in Communities;
CARDIA=
Coronary Artery Risk Development in Young Adults;
CI=
confidence interval;
CVRF=
cardiovascular risk factor;
DSST=
Digit Symbol Substitution Test;
OR=
odds ratio;
RAVLT=
Rey Auditory Verbal Learning Test

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received July 25, 2019.
  • Accepted in final form March 6, 2020.
  • © 2020 American Academy of Neurology
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