Exploiting Drug-Apolipoprotein E Gene Interactions in Hypertension to Preserve Cognitive Function: The 3-City Cohort Study
Date
2019-02-01
Authors
Tully, Phillip J.
Helmer, Catherine
Peters, Ruth
Tzourio, Christophe
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Volume Title
Publisher
Lippincott Williams & Wilkins Ltd.
Abstract
OBJECTIVES: The objective was to test the hypothesis that antihypertensive drugs have a differential effect
on cognition in carriers and noncarriers of the apolipoprotein ε4 (APOE4) polymorphism.
DESIGN: Prospective population-based cohort, France.
Setting and participants: A total of 3359 persons using antihypertensive drugs (median age 74 years, 62%
women) were serially assessed up to 10 years follow-up.
Measures: Exposure to antihypertensive drug use was established in the first 2 years. Cognitive function
was assessed at baseline, 2, 4, 7, and 10 years with a validated test battery covering global cognition,
verbal fluency, immediate visual recognition memory, processing speed, and executive function. Clinically significant change in cognitive function was determined using reliable change indices represented
as z scores and analyzed with linear mixed-models.
RESULTS: From 3359 persons exposed to antihypertensive drugs, 653 were APOE4 carriers (5.1% homozygous, 94.9% heterozygous) and median follow-up was 5.2 years (interquartile range 3.7e8.0). In APOE4
carriers, improved general cognitive function over time was associated with exposure to angiotensin
converting enzyme inhibitors [b ¼ .14; 95% confidence interval (CI) .06e.23, P ¼ .001] and angiotensin
receptor blockers (b ¼ .11; 95% CI .02e.21, P ¼ .019). Improved verbal fluency was associated with
angiotensin converting enzyme inhibitors (b ¼ .11; 95% CI .03e.20, P ¼ .012).
CONCLUSIONS: Renin-angiotensin-system blockade was associated with improved general cognitive function in APOE4 carriers. Findings did not support renin-angiotensin-system drugs’ lipophilicity or ability
to cross the blood-brain barrier as potential mechanisms. The findings have implications for selecting the
optimal antihypertensive drug in older populations at risk of cognitive decline and dementia
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Keywords
hypertension, antihypertensive agents, cognitive function, mild cognitive impairment, Alzheimer’s disease, renin-angiotensin system
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Source
Journal of the American Medical Directors Association
Type
Journal article
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2037-12-31
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