Midlife hypertension is associated with subsequent risk of dementia

Uncontrolled hypertension among individuals aged 45-65 years of age is associated with an increased risk of subsequent dementia, according to a relatively large prospective population-based cohort study that followed patients for almost 30 years.

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Even though previously published studies have not conclusively linked blood pressure control with a reduction in dementia risk, a second study, published simultaneously, did link blood pressure control with a smaller increase in white matter lesions, which are a marker of dementia risk. However, a reduction in total brain volume that accompanied this protection raised concern.

In the first of the two reports published Aug. 13 in JAMA, individuals 45-65 years of age participating in the Atherosclerosis Risk in Communities (ARIC) study were followed for cognitive function in relation to blood pressure. The baseline visit took place in 1987-1989. Cognitive function was also evaluated at the fifth visit, which took place in 2011-2013, and the sixth visit, which took place in 2016-2017.

At the sixth visit, the incidence of dementia among patients who were normotensive at baseline and also normotensive at the fifth visit was 1.31 per 100 person-years. For those with hypertension (greater than 140/90 mm Hg) at the fifth visit but normotensive at baseline, the incidence was 1.99 per 100 patient-years. For those with hypertension at both time points, the incidence was 4.26 per 100 patient-years.

When translated into hazard ratios, those with midlife and late-life hypertension were nearly 50% more likely to develop dementia (HR, 1.49) relative to those who remained normotensive. For those who had only midlife hypertension, the risk was also significantly increased (HR, 1.41) relative to those who remained normotensive at both time points.

Those with midlife hypertension but late-life hypotension were also found to be at greater risk of dementia (HR, 1.62) relative to those who remained normotensive.

These data support the premise that uncontrolled midlife hypertension increases risk of dementia but do not touch on whether blood pressure reductions reduce this risk. However, a second study published simultaneously provided at least some evidence that blood pressure control might offer some protection.

In this report, which is a substudy of the previously published Systolic Blood Pressure Intervention Trial (SPRINT) MIND trial, brain volume changes were evaluated via MRI in 449 of the more than 2,000 patients included in the previously published trial (Williamson JD et al. JAMA. 2019;321[6]:553-61).

After a median 3.4 years of follow-up, mean white matter lesion volume increased only 0.92 cm³ in patients receiving intensive systolic blood pressure control, defined as less than 120 mm Hg, versus 1.45 cm³ in those with higher systolic blood pressures.

These substudy data are encouraging, but it is important to recognize that the previously published and larger SPRINT MIND trial did not achieve its endpoint. In that study, the protection against dementia was nonsignificant (HR, 0.83; 95% confidence interval, 0.67-1.04).

In addition, the lower loss in white matter volume with intensive blood pressure lowering in the MRI substudy was accompanied with a greater loss in total brain volume (–30.6 vs. –26.9 cm³), which is considered a potentially negative effect.

As a result, the picture for risk management remains unclear, according to an editorial that accompanied publication of both studies.

“The important clinical question is whether changes of a few cubic millimeters in white matter hyperintensity volume or brain make a difference on brain function,” observed the author of the editorial, Shyam Prabhakaran, MD, of the department of neurology at the University of Chicago.

He believes that there are several findings from both studies that are “encouraging” in regard to blood pressure control for the prevention of dementia, but he also listed many unanswered questions, including why benefits observed to date have been so modest. He speculated that meaningful clinical benefits might depend on a multimodal approach that includes modification of other vascular risk factors, such as elevated lipids.

He also suggested that many issues regarding intensive blood pressure control for preventing dementia are unresolved, suggesting the need for more studies.

Not least, “later blood-pressure lowering interventions require careful monitoring for the potential cognitive harm associated with late-life hypotension,” Dr. Prabhakaran noted. Calling the effects of blood pressure control on brain health “nuanced,” he concluded that there is an opportunity for blood pressure modifications to prevent dementia, but stressed that optimal blood pressure targets for the purposes of preventing dementia are unknown.

The ARIC and SPRINT studies are supported by the National Institutes of Health. Several authors reported relationships with industry but no conflicts of interest relevant to this study.

SOURCES: Walker KA et al. JAMA. 2019;322(6):535-45; SPRINT MIND investigators. JAMA. 2019;322(6):524-34; Prabhakaran S. JAMA. 2019;322(6):512-3