The association between blood pressure and incident Alzheimer disease: a systematic review and meta-analysis

Abstract

Background: Many epidemiologic studies have considered the association between blood pressure (BP) and Alzheimer disease, yet the relationship remains poorly understood.

Methods: In parallel with work on the AlzRisk online database (www.alzrisk.org), we conducted a systematic review to identify all epidemiologic studies meeting prespecified criteria reporting on the association between hypertension, systolic BP, or diastolic BP and incident Alzheimer disease. When possible, we computed summary measures using random-effects models and explored potential heterogeneity related to age at BP assessment.

Results: Eighteen studies reporting on 19 populations met the eligibility criteria. We computed summary relative risks (RR(Σ)) for 3 measures of BP: hypertension (RR(Σ) = 0.97 [95% confidence interval = 0.80-1.16]); a 10-mm Hg increase in systolic BP (RR(Σ) = 0.95 [0.91-1.00]); and a 10-mm Hg increase in diastolic BP (RR(Σ) = 0.94 [0.85-1.04]). We were unable to compute summary estimates for the association between categories of systolic or diastolic BP and Alzheimer disease; however, there did not appear to be a consistent pattern across studies. After stratifying on age at BP assessment, we found a suggestion of an inverse association between late-life hypertension and Alzheimer disease and a suggestion of an adverse association between midlife diastolic hypertension and Alzheimer disease.

Conclusions: Based on existing epidemiologic research, we cannot determine whether there is a causal association between BP and Alzheimer disease. Selection bias and reverse causation may account for the suggested inverse association between late-life hypertension on Alzheimer disease, but, given the expected direction of these biases, they are less likely to account for the suggestion that midlife hypertension increases risk. We advocate continuing systematic review; the AlzRisk database entry on this topic (www.alzrisk.org), which was completed in parallel with this work, will be updated as new studies are published.

Figure 1

Flowchart describing the two-phase approach used to identify all eligible studies.

Figure 2

Individual and pooled estimates of the association between measures of hypertension and Alzheimer disease. The size of the box representing the point estimate for each study in the forest plot is proportional to the contributing weight of that study estimate to the summary estimate. Reference category is no hypertension.

Figure 3

Individual and pooled effect estimates of the association between a 10 mm Hg-increase in systolic BP (SBP) and Alzheimer disease. The size of the box representing the point estimate for each study in the forest plot is proportional to the contributing weight of that study estimate to the summary estimate.

Figure 4

Individual and pooled effect estimates of the association between a 10 mm Hg-increase in diastolic BP (DBP) and Alzheimer disease. The size of the box representing the point estimate for each study in the forest plot is proportional to the contributing weight of that study estimate to the summary estimate.

Figure 5

Individual estimates of the association between categories of systolic BP and Alzheimer disease.

Figure 6

Individual estimates of the association between categories of diastolic BP and Alzheimer disease.