Potential Cognitive Benefits of Intensive Blood Pressure Lowering
By Heather Nelson Cortes, PhD and Kevin C Maki, PhD
Currently there are no well-established clinical interventions for the prevention of mild cognitive impairment (MCI) or dementia. Alzheimer’s disease and dementia are expected to affect 115 million people worldwide by the year 20501. More than 75% of people over the age of 65 have hypertension, a modifiable risk factor that has been associated with the risk for developing MCI and dementia2-4. Vascular damage is commonly found in Alzheimer’s disease, along with the β-amyloid and tau pathology5-7, yet research has been inconclusive on the role of blood pressure (BP) reduction and risk for MCI and dementia.
Recently, results from the Systolic Blood Pressure Intervention Trial (SPRINT) Memory and Cognition in Decreased Hypertension (MIND) study were published from the parent SPRINT study8. SPRINT-MIND was designed to assess the effect of intensive blood pressure treatment/control on the risk for dementia. The primary outcome was the occurrence of adjudicated probable dementia. Secondary outcomes included adjudicated MCI and a composite outcome of MCI or probable dementia.
The parent SPRINT study was designed to test the effect of more intensive BP control on cardiovascular (primary end point), renal and cognitive outcomes in subjects with systolic blood pressure (SBP) greater than 130 mm Hg who had an increased cardiovascular risk but did not have diabetes or preexisting stroke9. In SPRINT, 9361 persons were randomized to either a standard treatment (SBP goal, <140 mm Hg; n = 4683) or to an intensive treatment (SBP goal, <120 mm Hg; n = 4678). After a median follow up of 3.26 years, SPRINT was stopped early because of the observed benefits in the primary outcome of cardiovascular disease events as well as reduced all-cause mortality9.
Of the 9361 subjects randomized in SPRINT, 91.5% (n = 8562) completed at least 1 follow-up cognitive assessment as part of SPRINT-MIND. The median intervention period was 3.34 years with a total median follow-up of 5.11 years, including time after the intervention ended. In the intensive treatment group, the primary outcome, adjudicated probable dementia, occurred in 149 subjects compared to 176 subjects in the standard treatment group (7.2 vs. 8.6 cases per 1000 person-years; hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.67-1.04, p = 0.10). Intensive BP control did significantly reduce the risk of MCI (14.6 vs. 18.3 cases per 1000 person-years; HR, 0.81; 95% CI, 0.69-0.95, p = 0.007) and the combined rate of MCI or probable dementia (20.2 vs. 24.1 cases per 1000 person-years; HR, 0.85; 95% CI, 0.74-0.97, p = 0.01)8.
Comment. SPRINT-MIND did not demonstrate a statistically significant effect on the primary outcome of adjudicated probable dementia, possibly due to the early termination of SPRINT and the resulting loss of statistical power. The study did, however, show reductions in the secondary outcomes of incident MCI (19% lower risk) and the combined outcome of MCI or probable dementia (15% lower risk). While it is disappointing that the primary outcome showed no significant benefit (a non-significant 17% lower incidence in the intensive BP control group), the reduction in risk for the secondary outcomes is encouraging and suggests a plausible link between intensive BP treatment and prevention of MCI and dementia. These results support the need for additional research to confirm and extend the SPRINT-MIND findings. Because dementia and MCI have several risk factors in common with cardiometabolic diseases such as heart disease, stroke and type 2 diabetes, the SPRINT-MIND findings also suggest that there might be potential for reductions in cardiometabolic risk factors beyond BP to play a role in maintaining optimal brain health10.
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