Slight processing speed worsening seen, but not clinically relevant

Higher versus lower blood pressure goals made no difference in memory testing, and a slight processing speed worsening in people with more intensive blood pressure treatment was not clinically relevant, a pre-planned analysis of SPRINT trial data found.

“Intensive anti-hypertensive treatment to lower systolic blood pressure (goal of less than 120 mm Hg) did not result in a clinically relevant difference in individual cognitive domains compared with standard treatment (goal of less than 140 mm Hg),” wrote Stephen Rapp, PhD, of Wake Forest University in Winston-Salem, North Carolina, and coauthors in Lancet Neurology.

“This finding suggests that hypertension probably affects multiple regions and systems in the brain and therefore produces heterogeneous cognitive effects,” they noted.

SPRINT was an open-label, randomized controlled trial comparing systolic blood pressure targets of less than 140 mm H versus less than 120 mm Hg in patients over 50 with systolic blood pressure over 130 mm Hg. The study terminated early due to the benefit observed on primary cardiovascular outcomes in the intensive treatment group.

A sub-study (SPRINT MIND) suggested that intensive control of systolic blood pressure did not reduce its primary outcome of adjudicated probable dementia, but did reduce risk for the secondary outcome of mild cognitive impairment (HR 0.81, 95% CI 0.69-0.95).

The present analysis looked at domain-specific composite cognitive test scores in the standard vs intensive treatment groups.

After a median 4.1 years follow-up, no difference between intensive vs standard treatment groups was seen in memory; both had a similar annual decline in the mean standardized composite score with a between-group difference of 0.004 points (95% CI –0.012 to 0.004; P=0.33). In processing speed, the intensive treatment group declined more than the standard treatment group with a between-group difference on mean standardized composite score of –0.010 (95% CI –0.017 to –0.002; P=0.02).

Additional evaluations for language, executive function, and global cognitive function also did not show significant between-group differences.

“Results from the SPRINT sub-study suggest that a healthy skepticism is needed about the use of intensive treatment to lower systolic blood pressure in older adults to prevent cognitive decline and dementia,” wrote Philip Gorelick, MD, and Farzaneh Sorond, MD, both of Northwestern University in Chicago, in an accompanying editorial. “There are several trials of drugs to lower blood pressure, although most have shown inconsistent results in relation to reduction of cognitive disorders or other key cognition-specific outcomes.”

“Trials that do not show a protective effect might be difficult to reconcile with results from the few trials that showed a benefit on the basis of disparate study methods, but they do serve as a note of caution for future research,” they continued. “Encouraging results from observational studies that have focused on lowering blood pressure in people in early life and midlife and from meta-analyses of trials on intensive lowering of systolic blood pressure (e.g., by ≥10 mm Hg), should motivate future study design in terms of preserving cognition.”

An optimal level of blood pressure control for overall health is not known, or whether management should focus on numerical reduction goals like 10 mm Hg, for example. Any one choice may in principle bring benefits in one domain and harm in another: a lower target may reduce cardiovascular events (including stroke) but lead to hyperperfusion of the brain with short- or long-term consequences, including syncope and impaired cognition. Findings with respect to cognition have been mixed.

In addition to the SPRINT MIND findings noted for probable dementia and MCI, a subset of patients also had MRI at baseline and 4-year follow-up. Another analysis found small differences that favored intensive treatment (smaller increase in cerebral white matter lesion volume) but also standard treatment (less decrease in total brain volume).

Another important question is whether blood pressure control in earlier life (young adulthood or middle age) is capable of preventing cognitive impairment, while similar targets in later life may not be. The 2020 Lancet Commission report on dementia prevention, intervention, and care noted a goal to maintain systolic BP of 130 mm Hg or less in midlife from around age 40 years, saying “anti-hypertensive treatment for hypertension is the only known effective preventive medication for dementia.”

In the present study, Rapp and colleagues studied a subset of SPRINT participants enrolled from November 2010 to December 2012 (n=2,921; median age 68.4 and 37% women), with 1,448 receiving intensive treatment and 1,473 standard treatment.

Baseline and biennial evaluations to 4-year follow-up included collection of data for a composite memory score (Logical Memory I and II, Modified Rey-Osterrieth Complex Figure immediate recall, and Hopkins Verbal Learning Test-Revised delayed recall) and a composite processing speed score (Trail Making Test and Digit Symbol Coding).

Memory score mean annual decline was –0.005 points, 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. Processing score mean annual decline was –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.

Limitations of the study include the early termination of the intervention based on favorable interactions in the intensive treatment group, which may have affected power to detect other outcomes studied in SPRINT and sub-studies.

  1. Higher versus lower blood pressure goals made no difference in memory testing, and a slight processing speed worsening in people with more intensive blood pressure treatment was not clinically relevant, a pre-planned analysis of SPRINT trial data found.

  2. The finding suggests hypertension probably affects multiple regions and systems in the brain and produces heterogeneous cognitive effects, the researchers said.

Paul Smyth, MD, Contributing Writer, BreakingMED™

Funding came from the National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Aging, National Institute of Neurological Disorders and Stroke, and the Alzheimer’s Association.

Rapp received support from NIH and from the Alzheimer’s Association.

Gorelick serves on a data safety and monitoring board for Novartis for a study of LCZ 696 administration for the preservation of cognition in heart failure, for which his primary employer receives honoraria. Sorond declares no competing interests.

Cat ID: 130

Topic ID: 82,130,400,404,494,130,361,192,255,916,925