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Original Investigation |

Midlife Hypertension and 20-Year Cognitive Change:  The Atherosclerosis Risk in Communities Neurocognitive Study

Rebecca F. Gottesman, MD, PhD1,2; Andrea L. C. Schneider, MD, PhD2; Marilyn Albert, PhD1; Alvaro Alonso, MD, PhD3; Karen Bandeen-Roche, PhD4; Laura Coker, PhD5; Josef Coresh, MD, PhD2; David Knopman, MD6; Melinda C. Power, ScD2; Andreea Rawlings, MS2; A. Richey Sharrett, MD, DrPH2; Lisa M. Wruck, PhD7; Thomas H. Mosley, PhD8
[+] Author Affiliations
1Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland
2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
3Division of Epidemiology and Community Health, University of Minnesota, Minneapolis
4Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
5Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina
6Department of Neurology, Mayo Clinic, Rochester, Minnesota
7Department of Biostatistics, University of North Carolina at Chapel Hill
8Department of Medicine, University of Mississippi Medical Center, Jackson
JAMA Neurol. 2014;71(10):1218-1227. doi:10.1001/jamaneurol.2014.1646.
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Importance  Hypertension is a treatable potential cause of cognitive decline and dementia, but its greatest influence on cognition may occur in middle age.

Objective  To evaluate the association between midlife (48-67 years of age) hypertension and the 20-year change in cognitive performance.

Design, Setting, and Participants  The Atherosclerosis Risk in Communities cohort (1990-1992 through 2011-2013) underwent evaluation at field centers in Washington County, Maryland, Forsyth County, North Carolina, Jackson, Mississippi, and the Minneapolis, Minnesota, suburbs. Of 13 476 African American and white participants with baseline cognitive data, 58.0% of living participants completed the 20-year cognitive follow-up.

Exposures  Hypertension, prehypertension, or normal blood pressure (BP) at visit 2 (1990-1992) constituted the primary exposure. Systolic BP at visit 2 or 5 (2011-2013) and indication for treatment at visit 2 based on the Eighth Joint National Committee (JNC-8) hypertension guidelines constituted the secondary exposures.

Main Outcomes and Measures  Prespecified outcomes included the 20-year change in scores on the Delayed Word Recall Test, Digit Symbol Substitution Test, and Word Fluency Test and in global cognition.

Results  During 20 years, baseline hypertension was associated with an additional decline of 0.056 global z score points (95% CI, −0.100 to −0.012) and prehypertension was associated nonsignificantly with 0.040 more global z score points of decline (95% CI, −0.085 to 0.005) compared with normal BP. Individuals with hypertension who used antihypertensives had less decline during the 20 years than untreated individuals with hypertension (−0.050 [95% CI, −0.003 to −0.097] vs −0.079 [95% CI, −0.156 to −0.002] global z score points). Having a JNC-8–specified indication for initiating antihypertensive treatment at baseline was associated with a greater 20-year decline (−0.044 [95% CI, −0.085 to −0.003] global z score points) than not having an indication. We observed effect modification by race for the continuous systolic BP analyses (P = .01), with each 20–mm Hg increment at baseline associated with an additional decline of 0.048 (95% CI, −0.074 to −0.022) points in global cognitive z score in whites but not in African Americans (decline, −0.020 [95% CI, −0.026 to 0.066] points). Systolic BP at the end of follow-up was not associated with the preceding 20 years of cognitive change in either group. Methods to account for bias owing to attrition strengthened the magnitude of some associations.

Conclusions and Relevance  Midlife hypertension and elevated midlife but not late-life systolic BP was associated with more cognitive decline during the 20 years of the study. Greater decline is found with higher midlife BP in whites than in African Americans.

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Figure 1.
Timeline for the Atherosclerosis Risk in Communities Study

Visits, assessments, and numbers of participants are tabulated.

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Figure 2.
Adjusted Association of Visit 2 (1990-1992) Systolic Blood Pressure Categories and Linear Systolic Blood Pressure With 20-Year Cognitive Change Among Whites

Models are adjusted for age, square of age, sex, center (North Carolina, Minnesota, and Maryland for whites; North Carolina and Mississippi for African Americans), educational level (<high school; high school, General Educational Development Test, or vocational school; or college, graduate school, or professional school), body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]; <25, 25 to <30, or ≥30), diabetes mellitus, alcohol consumption (never, former, or current), smoking status (never, former, or current), apolipoprotein E (APOE) ε4 genotype (0, 1, or 2 alleles), history of stroke, time as a linear spline with knot at 6 years, age by time spline terms, square of age by time spline terms, sex by time spline terms, center by time spline terms, education by time spline terms, BMI by time spline terms, diabetes mellitus by time spline terms, smoking status by time spline terms, and APOE ε4 genotype by time spline terms. Systolic blood pressure categories are defined as less than 110, 110 to less than 120 (reference group; second data marker), 120 to less than 140, 140 to less than 160, and 160 or more mm Hg. Data points are shown at the midpoint of the categories for the 110 to 120–, 120 to 140–, and 140 to 160–mm Hg groups (115, 130, and 150 mm Hg, respectively) but at the median values for the 2 extreme groups (<110 and ≥160 mm Hg) because of the large range of values seen in each of these groups. A, Global z score. B, Delayed Word Recall Test (DWRT) z score. C, Digit Symbol Substitution Test (DSST) z score. D, Word Fluency Test (WFT) z score. Data markers indicate categorical β values; lines, linear fit; and error bars, categorical 95% CIs.

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