Effect of Intensive Blood Pressure Control on Subtypes of Mild Cognitive Impairment and Risk of Progression From SPRINT Study

Sarah A. Gaussoin MS; Nicholas M. Pajewski PhD; Gordon Chelune PhD; Maryjo L. Cleveland MD; Michael G. Crowe PhD; Lenore J. Launer PhD; Alan J. Lerner MD; Jennifer Martindale-Adams EdD; Linda O. Nichols PhD; Paula K. Ogrocki PhD; Bonnie C. Sachs PhD; Kaycee M. Sink MD; Mark A. Supiano MD; Virginia G. Wadley PhD; Valerie M. Wilson MD; Clinton B. Wright MD; Jeff D. Williamson MD; David M. Reboussin PhD; Stephen R. Rapp PhD


J Am Geriatr Soc. 2022;70(5):1384-1393. 

In This Article

Abstract and Introduction


Background: To examine the effect of intensive blood pressure control on the occurrence of subtypes of mild cognitive impairment (MCI) and determine the risk of progression to dementia or death.

Methods: Secondary analysis of a randomized trial of community-dwelling adults (≥50 years) with hypertension. Participants were randomized to a systolic blood pressure (SBP) goal of <120 mm Hg (intensive treatment; n = 4678) or <140 mm Hg (Standard treatment; n = 4683). Outcomes included adjudicated MCI, MCI subtype (amnestic, non-amnestic, multi-domain, single domain), and probable dementia. Multistate survival models were used to examine transitions in cognitive status accounting for the competing risk of death.

Results: Among 9361 randomized participants (mean age, 67.9 years; 3332 women [35.6%]), 640 participants met the protocol definition for MCI, with intensive treatment reducing the risk of MCI overall (hazard ratio [HR], 0.81 [95% confidence interval {CI}, 0.69–0.94]), as previously reported. This effect was largely reflected in amnestic subtypes (HR, 0.78 [95% CI, 0.66–0.92]) and multi-domain subtypes (HR, 0.78 [95% CI, 0.65–0.93]). An adjudication of MCI, as compared with normal cognitive function, substantially increased the probability of progressing to probable dementia (5.9% [95% CI: 4.5%–7.7%] vs. 0.6% [95% CI: 0.3%–0.9%]) and to death (10.0% [95% CI: 8.3%–11.9%] vs. 2.3% [95% CI: 2.0%–2.7%]) within 2 years.

Conclusions: Intensive treatment reduced the risk for amnestic and multi-domain subtypes of MCI. An adjudication of MCI was associated with increased risk of progression to dementia and death, highlighting the relevance of MCI as a primary outcome in clinical and research settings.


Mild cognitive impairment (MCI) represents a clinical state on the continuum of neurocognitive functioning between normal functioning and dementia.[1] MCI is a risk factor for dementia, with an overall annual conversion rate of approximately 7%.[2] Given the general lack of efficacy in treating dementia directly,[3,4] attention has turned toward identifying therapeutic strategies for the prevention and treatment of MCI. Phenotyping MCI has identified subtypes based on the presence or absence of memory deficits (amnestic vs. non-amnestic) and on the breadth of deficits (single vs. multiple cognitive domains).[5] A meta-analysis of 41 studies showed that individuals with amnestic MCI and multi-domain MCI have cumulative and annual conversion rates to dementia that are significantly higher than non-amnestic MCI, suggesting that MCI may represent several disease groups.[2] Thus, it becomes important to know if therapeutic interventions differentially affect MCI subtypes, which could lead to greater treatment precision.

Blood pressure lowering as a treatment for hypertension, a modifiable risk factor for MCI and dementia,[6] is the only pharmacologic strategy with randomized trial evidence demonstrating reductions in cognitive impairment.[7–9] The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated a significant reduction in the occurrence of MCI in adults with hypertension who were randomly assigned to intensive systolic blood pressure (BP) control (<120 mm Hg) compared with those assigned to standard BP control (<140 mm Hg).[10] Given the phenotypic heterogeneity inherent to MCI, questions remain about the possible differential effect of intensive BP treatment on subtypes of MCI, as well as the influence of treatment on the progression to more severe impairment. In the present work, we use data from SPRINT in a secondary analysis to examine these issues.