Cognitive Function Domains Not Improved With Lowered Systolic Blood Pressure

Author(s):

The researchers concluded that the effect of lowered blood pressure might not be evident in specific domains of cognitive function, but instead distributed across multiple domains.

Stephen R. Rapp, PhD

Results from a substudy of the Systolic Blood Pressure Intervention Trial (SPRINT; NCT01206062) revealed that intensive treatment to lower systolic blood pressure did not result in a clinically relevant difference on memory or processing speed compared with standard treatment.¹

Study author Stephen R. Rapp, PhD, clinical psychologist, Wake Forest School of Medicine, and colleagues found that after a median follow-up of 4.1 years (interquartile range [IQR], 3.7–5.8), there was no between-group difference in memory, with an annual decline in mean standardized domain score of –0.005 (95% CI, –0.010 to 0.001) in the intensive treatment group and –0.001 (95% CI, –0.006 to 0.005) in the standard treatment group (P = 0.33).

"The strengths of this substudy include the large sample size, the length of treatment and follow-up, the use of a comprehensive battery of validated cognitive measures, and the inclusion of multiple major domains of cognitive function, each with multiple component measures,” Rapp and colleagues concluded.

Patients were evaluated on composite scores for memory, including Logical Memory I and II, Modified Rey-Osterrieth Complex Figure, and Hopkins Verbal Learning Test-Revised. Processing speeds measured by the Trail Making Test and Digit Symbol Coding were also used as primary outcomes.

Rapp and co-investigators noted that the mean standardized processing speed domain scores declined more in the intensive treatment group (between-group difference, –0.010; 95% CI, –0.017 to –0.002; P = .02), with an annual decline of –0.025 (95% CI, –0.030 to –0.019) for the intensive treatment group and –0.015 (95% CI, –0.021 to 0.009) for the standard treatment group.

There was no evidence of a differential treatment effect with respect to the incidence of cardiovascular events, all cause-mortality, and declines in kidney function between the cognitive function subgroup and those not in the cognitive function subgroup.

The open-label, randomized, controlled study featured a subset of 2921 participants (mean age, 68.4 years [standard deviation (SD), 8.6], 1080 [37%] women), 1448 of which received intensive treatment and 1473 who received standard treatment. Intensive treatment was defined as a systolic blood pressure goal of less than 120 mm Hg whereas standard treatment was 140 mm Hg.

Secondary analyses of the individual cognitive tests within the processing speed domain indicated that only the Trail Making Test showed significant differences between the groups. Untransformed mean times increased on the Trail Making Test, indicating poorer performance, by 0.43 seconds per year (95% CI, 0.30–0.57) in the intensive treatment group compared to 0.12 seconds per year (95% CI, 0.12–0.26) in the standard treatment group.

Exploratory outcomes such as language (P = .84), executive function (P = .40), and global cognitive function (P = .089), showed small declines but were not found to be significant between the standard and intensive treatment groups.

Due to the benefit observed in the overall SPRINT primary outcome, the composite of cardiovascular events, the main study was terminated early. As such, Rapp and his colleagues also conducted a post-hoc analysis that examined whether early cessation of the SPRINT study intervention affected findings, but results were largely unchanged with the exclusion of extended follow-up visits.

Other notable data within the study included the similar rate of mild cognitive impairment (MCI) in those randomly assigned to the intensive treatment (107 [8%]) compared to those on standard treatment (105 [7.7%]; hazard ratio [HR], 1.08; 95% CI, 0.82–1.42). In contrast, participants not included in the substudy had fewer cases of MCI with intensive treatment (180 [6.1%] vs 248 [8.5] cases; HR, 0.72; 95% CI, 0.59–0.87; P = .031).

Previously published data from the SPRINT-MIND trial, a related parent study, showed that intensive control of systolic blood pressure significantly reduced the occurrence of MCI, but not probable dementia. Data indicated that in the intensive treatment group (n = 4678), there were 7.2 cases of probable dementia per 1000 person-years (149 cases), compared to 8.6 cases per 1000 person-years (176 cases) in the standard treatment group (n = 4683), over the total median follow-up of 5.11 years (HR, 0.83; 95% CI, 0.67–1.04). In total, 9361 participants with a mean age of 67.9 years were randomized to either the intensive group or the standard treatment group.²

REFERENCES

1. Rapp SR, Gaussoin SA, Sachs BC, et al. Effects of intensive versus standard blood pressure control on domain-specific cognitive function: a substudy of the SPRINT randomized controlled trial. Published online November 1, 2020. Lancet Neurol. doi: 10.1016/S1474-4422(20)30319-7

2. Williamson Jd, Pajewski NM, Auchus AP, et al. Effect of intensive vs standard blood pressure control on probable dementia: a randomized clinical trial. JAMA. Published online January 28, 2019. doi:10.1001/jama.2018.21442.