Association between blood pressure levels and cognitive impairment in older women: a prospective analysis of the Women's Health Initiative Memory Study

Abstract

Background: Whether blood pressure (BP), and at what level of controlled BP, reduces risk of cognitive impairment remains uncertain. We investigated the association of BP and hypertension treatment status with mild cognitive impairment and dementia in older women.

Methods: We prospectively analysed a sample of 7207 community-dwelling women aged 65-79 years participating in the Women's Health Initiative Memory Study (WHIMS). Participants were recruited between May 28, 1996, and Dec 13, 1999, at 39 US clinical centres, and they were followed up until Dec 31, 2019. Cognitive function was assessed annually. Mild cognitive impairment and probable dementia were defined through a centralised adjudication process. BP was measured by trained and certified staff at baseline. Pulse pressure (PP) was calculated as systolic BP (SBP) minus diastolic BP. Hypertension was defined using the American Heart Association 2017 Guideline for High BP in Adults. Outcomes were (1) mild cognitive impairment, (2) probable dementia, and (3) cognitive loss (the combined endpoint of either mild cognitive impairment or probable dementia, or both). We estimated hazard ratios (HRs) to assess the association between hypertension, SBP, and PP with the risk of study outcomes using Cox proportional hazards regression models, with adjustment for key covariates.

Findings: During a median follow-up of 9 years (IQR 6-15), 1132 (15·7%) participants were classified as mild cognitive impairment, 739 (10·3%) as probable dementia, and 1533 (21·3%) as cognitive loss. The incidence rates per 1000 person-years were 15·3 cases (95% CI 14·4-16·2) for mild cognitive impairment, 9·7 cases (9·0-10·4) for probable dementia, and 20·3 (19·3-21·3) for cognitive loss. Elevated SBP and PP were significantly associated with increased risk of mild cognitive impairment and cognitive loss (test for trends across SBP and PP strata, p<0·01). Individuals with hypertension, but with controlled SBP of less than 120 mm Hg did not have a significantly increased risk of mild cognitive impairment (HR 1·33, 95% CI 0·98-1·82, p=0·071), and of cognitive loss (1·09, 0·82-1·44, p=0·57) compared with normotension. Individuals on anti-hypertensive treatment with PP of less than 50 mm Hg did not have a significantly higher risk of mild cognitive impairment (1·26, 0·98-1·62, p=0·07) and of cognitive loss (1·17, 0·94-1·46, p=0·16). There were no significant associations between hypertension, SBP, or PP and probable dementia.

Interpretation: Results of our study show significant associations of hypertension and elevated SBP and PP levels with risk of mild cognitive impairment and the combined endpoint of either mild cognitive impairment or probable dementia, suggesting that intensive control of hypertension, SBP, and PP can preserve cognitive health in older women.

Funding: National Heart, Lung, and Blood Institute, National Institutes of Health, and US Department of Health and Human Services.

Figure 1:

Sample size of the study participants

Figure 2:. Relative hazards of SBP for cognitive loss and mild cognitive impairment (A, B), and of PP for cognitive loss and mild cognitive impairment (C,D)

Solid line: the estimated relative hazards for cognitive loss compared with the reference value as a function of SBP levels (A and B) or of PP levels (C and D). Dotted lines are the 95% CIs of the relative hazard lines. Summary hazard ratios are calculated for each 10 mm Hg increase in SBP or PP. Overall, an increase in every 10 mm Hg of SBP was associated with an increased risk of cognitive loss by 5%, and an increased risk of mild cognitive impairment by 4%. An increase in every 10 mm Hg of PP was associated with an increased risk of cognitive loss and of mild cognitive impairment by 7%. SBP=systolic blood pressure. PP=pulse pressure. HR=hazard ratio.