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Original Investigation
March 8, 2021

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

Author Affiliations
  • 1Department of Radiology, University of Pennsylvania, Philadelphia
  • 2Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, North Carolina
  • 3Intramural Stroke Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland
  • 4Intramural Research Program, National Institute on Aging, Baltimore, Maryland
  • 5Department of Neurology, University of Pennsylvania, Philadelphia
  • 6Section of Gerontology and Geriatric Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina
  • 7Department of Diagnostic Medicine, Dell Medical School, University of Texas at Austin, Austin
JAMA Neurol. 2021;78(5):568-577. doi:10.1001/jamaneurol.2021.0178
Key Points

Question  Is intensive systolic blood pressure control associated with changes in the progression of Alzheimer disease–related magnetic resonance imaging biomarkers compared with standard blood pressure control?

Findings  In this secondary analysis of a randomized clinical trial that included 454 adults with hypertension with follow-up magnetic resonance imaging, intensive treatment was associated with small but statistically significant larger decreases in hippocampal volume but was not associated with any other biomarker of Alzheimer disease neurodegeneration.

Meaning  There is no consistent or clinically meaningful difference in magnetic resonance imaging biomarkers of Alzheimer disease between intensive and standard blood pressure treatment.


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  ClinicalTrials.gov Identifier: NCT01206062

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