Intensive blood-pressure control slowed white matter disease in adults age 75 and older
Intensive lowering of systolic blood pressure slowed white matter disease in adults age 75 and older with high blood pressure after three years of treatment, according to an NIA-funded clinical trial recently published in Circulation.
Several studies have suggested that people with high blood pressure have a greater chance of accumulating white matter lesions and experiencing later-in-life cognitive impairment and dementia.
The clinical trial, called Intensive Versus Standard Ambulatory Blood Pressure Lowering to Prevent Functional Decline In the Elderly (INFINITY), compared intensive systolic blood pressure control (130 mmHg or lower) with standard control (145 mmHg or lower) in 199 adults age 75 or older who had high blood pressure and white matter lesions that were visible on magnetic resonance imaging. Blood pressure was managed with one or more medications and monitored over 24 hours using a small digital device that took readings while participants went about their daily activities. Compared with clinic-based measurements, these “ambulatory” blood pressure readings provided for closer monitoring of blood-pressure fluctuations and more refined medication adjustments to help participants achieve their assigned blood pressure target.
The researchers found that, after three years of treatment, further accumulation of white matter lesions was reduced by 40% in the intensive-control group compared with the standard-control group. The intensive-control group also had fewer nonfatal cardiovascular events such as heart attack, heart failure and stroke.
However, there were no differences between the two groups in cognitive performance or mobility as measured by gait speed, balance tests and other measures. According to the researchers, this result could be due to the study’s short three-year duration. White matter deterioration progresses slowly over decades before functional impairments appear.
The results from the study provide further insights into the importance of blood pressure control as a way to prevent progression of white matter disease — damage to small blood vessels in the brain — and dementia, according to an accompanying editorial by Rebecca F. Gottesman, M.D., Ph.D., of the Johns Hopkins University School of Medicine. The results also suggest that intensive blood pressure control is safe in people with pre-existing white matter disease.
INFINITY builds on the results of a large, randomized clinical trial called the Systolic Blood Pressure Intervention Trial (SPRINT) and a substudy called SPRINT Memory and Cognition in Decreased Hypertension (SPRINT-MIND). SPRINT found that in adults 50 years and older with high blood pressure, intensive systolic blood pressure management to less than 120 mmHg, compared with a standard target of less than 140 mmHg, reduced risk of cardiovascular events and overall risk of death. SPRINT-MIND found that intensive control reduced incidence of mild cognitive impairment, a common precursor to dementia, but did not prevent dementia itself. A second SPRINT-MIND substudy found that intensive control slowed accumulation of white matter lesions in participants.
INFINITY and SPRINT differed in several ways. INFINITY was a much smaller trial than SPRINT, its participants were about 12 years older (mean ages, 80.5 and 67.9 years, respectively), and its blood pressure targets for both the standard and intensive control groups were less strict. Furthermore, INFINITY specifically recruited participants with pre-existing white matter lesions who, overall, had more white matter disease at the study start than SPRINT participants. Also, INFINITY used ambulatory blood pressure monitoring while SPRINT used clinic-based monitoring.
Despite these differences, INFINITY “further supports a similar approach in this population [age 75 and older] as in the rest of the population, with lower blood pressure being more ideal,” the editorial states. Future studies could focus on the ideal time of life to control blood pressure to maximize its benefits and the mechanisms by which blood-pressure control might forestall cognitive decline and dementia.
The study was funded by NIA grant R01AG022092.
These activities relate to NIA’s AD+ADRD Research Implementation Milestones:
- 2.A: "Create new research programs that use data-driven, systems-based approaches to integrate the study of fundamental biology of aging with neurobiology of aging and research on neurodegeneration, AD, and AD-related dementias to better understand the mechanism(s) of vulnerability and resilience in AD across all levels of biologic complexity (from cellular to population level) and to gain a deeper understanding of the complex biology and integrative physiology of healthy and pathologic brain aging."
- 8.B: "Increase investment in clinical trials that robustly test a variety of lifestyle interventions."
White WB, et al. Effects of intensive versus standard ambulatory blood pressure control on cerebrovascular outcomes in older people (INFINITY). Circulation. 2019;140(20):1626-1635. doi: 10.1161/CIRCULATIONAHA.119.041603.
Gottesman, RF. To INFINITY and beyond: What have we learned and what is still unknown about blood pressure lowering and cognition? Circulation. 2019;140(20): 1636-1638. doi: 10.1161/CIRCULATIONAHA.119.042827.