Association of Intensive vs Standard Blood Pressure Control With Magnetic Resonance Imaging Biomarkers of Alzheimer Disease: Secondary Analysis of the SPRINT MIND Randomized Trial

JAMA Neurol. 2021 May 1;78(5):568-577. doi: 10.1001/jamaneurol.2021.0178.


Importance: Meta-analyses of randomized clinical trials have indicated that improved hypertension control reduces the risk for cognitive impairment and dementia. However, it is unclear to what extent pathways reflective of Alzheimer disease (AD) pathology are affected by hypertension control.

Objective: To evaluate the association of intensive blood pressure control on AD-related brain biomarkers.

Design, setting, and participants: This is a substudy of the Systolic Blood Pressure Intervention Trial (SPRINT MIND), a multicenter randomized clinical trial that compared the efficacy of 2 different blood pressure-lowering strategies. Potential participants (n = 1267) 50 years or older with hypertension and without a history of diabetes or stroke were approached for a brain magnetic resonance imaging (MRI) study. Of these, 205 participants were deemed ineligible and 269 did not agree to participate; 673 and 454 participants completed brain MRI at baseline and at 4-year follow-up, respectively; the final follow-up date was July 1, 2016. Analysis began September 2019 and ended November 2020.

Interventions: Participants were randomized to either a systolic blood pressure goal of less than 120 mm Hg (intensive treatment: n = 356) or less than 140 mm Hg (standard treatment: n = 317).

Main outcomes and measures: Changes in hippocampal volume, measures of AD regional atrophy, posterior cingulate cerebral blood flow, and mean fractional anisotropy in the cingulum bundle.

Results: Among 673 recruited patients who had baseline MRI (mean [SD] age, 67.3 [8.2] years; 271 women [40.3%]), 454 completed the follow-up MRI at a median (interquartile range) of 3.98 (3.7-4.1) years after randomization. In the intensive treatment group, mean hippocampal volume decreased from 7.45 cm3 to 7.39 cm3 (difference, -0.06 cm3; 95% CI, -0.08 to -0.04) vs a decrease from 7.48 cm3 to 7.46 cm3 (difference, -0.02 cm3; 95% CI, -0.05 to -0.003) in the standard treatment group (between-group difference in change, -0.033 cm3; 95% CI, -0.062 to -0.003; P = .03). There were no significant treatment group differences for measures of AD regional atrophy, cerebral blood flow, or mean fractional anisotropy.

Conclusions and relevance: Intensive treatment was associated with a small but statistically significant greater decrease in hippocampal volume compared with standard treatment, consistent with the observation that intensive treatment is associated with greater decreases in total brain volume. However, intensive treatment was not associated with changes in any of the other MRI biomarkers of AD compared with standard treatment.

Trial registration: Identifier: NCT01206062.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / pathology*
  • Alzheimer Disease / physiopathology*
  • Antihypertensive Agents / therapeutic use
  • Biomarkers / analysis
  • Blood Pressure / drug effects
  • Blood Pressure / physiology*
  • Brain / drug effects
  • Brain / pathology
  • Brain / physiopathology
  • Cognitive Dysfunction / complications
  • Cognitive Dysfunction / drug therapy
  • Cognitive Dysfunction / pathology*
  • Female
  • Humans
  • Hypertension / drug therapy
  • Magnetic Resonance Imaging* / methods
  • Male
  • Middle Aged
  • Risk Factors


  • Antihypertensive Agents
  • Biomarkers

Associated data