Long-Term Effect of Intensive vs Standard Blood Pressure Control on Mild Cognitive Impairment and Probable Dementia in SPRINT

BACKGROUND AND OBJECTIVES: The Systolic Blood Pressure Intervention Trial suggested that intensive lowering of systolic blood pressure (SBP) decreases the risk of developing dementia. However, an insufficient number of probable dementia cases stemming from the trial's early termination made results inconclusive. The goal of this study was to estimate the effect of intensive vs standard SBP lowering on the longer term incidence of cognitive impairment leveraging extended follow-up for cognitive status. METHODS: This is a prespecified secondary analysis of a randomized clinical trial. Between 2010 and 2013, patients aged 50 years and older with hypertension and increased cardiovascular risk excluding those with diabetes mellitus or history of stroke were recruited from 102 clinics in the United States and Puerto Rico. Participants were randomized to a SBP goal of <120 mm Hg (intensive treatment) or <140 mm Hg (standard treatment) and received treatment for 3.3 years. In-person cognitive assessment follow-up occurred through July 2018. Continued ascertainment of cognitive status by telephone began in December 2019 for participants who had not withdrawn consent or been previously adjudicated with probable dementia, but provided consent for future research. Data were analyzed using survival analyses. RESULTS: Of 9,361 randomized participants, 7,221 (77%) were eligible to be re-contacted. Cognitive status of 4,232 (59%) was ascertained (mean age 67 years, 36% female). We accrued a total of 216 new cases of probable dementia, less than our target of 326. Over a median follow-up of 7 years, 248 participants of the intensive treatment group (8.5 per 1,000 person-years) were adjudicated with probable dementia, compared with 293 participants (10.2 per 1,000 person-years) in the standard treatment group (hazard ratio HR, 0.86; 95% CI, 0.72-1.02). Consistent with earlier results from the trial, the rate of both mild cognitive impairment (MCI; HR, 0.87 95% CI, 0.76-1.00) and a composite of MCI or probable dementia was lower with intensive treatment (HR, 0.89; 95% CI, 0.79, 0.99). DISCUSSION: Among ambulatory adults with hypertension and high cardiovascular risk, intensive treatment vs standard treatment of SBP for 3.3 years resulted in a lower risk of MCI and cognitive impairment including MCI or probable dementia, but not for probable dementia alone. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that intensively reducing SBP (target <120 mm Hg) decreases the risk of cognitive impairment in individuals aged 50 years and older with hypertension. CLINICAL TRIAL INFORMATION: Clinical trial number NCT01206062.