Link Between Abnormal Blood Pressure, Dementia Risk Poses Treatment Conundrum

Over the last 20 years, several large studies have shown that high blood pressure in middle age has a negative impact on cognition later in life and may be a risk factor for developing dementia. Researchers have begun to drill down into the data, and two analyses in JAMA have revealed clues about the interplay between blood pressure, cognition, and brain health.

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Researchers in the first study analyzed data from a substudy of the Systolic Blood Pressure Intervention Trial (SPRINT). SPRINT was a five-year study that sought to determine whether aggressively lowering blood pressure would decrease stroke, heart disease, the progression of chronic kidney disease, and age-related cognitive decline. In the substudy, 449 patients aged 50 years or older with high blood pressure were randomized to either intensive blood pressure management with a target systolic measurement of less than 120 mm Hg or standard blood pressure management with a target systolic measurement of less than 140 mm Hg.

“While there is general evidence that high blood pressure is related to cognitive impairment and dementia, there are few clinical trials directly showing that treating hypertension decreases subsequent risk of dementia and brain damage,” said researcher R. Nick Bryan, M.D., Ph.D., chair of the Department of Diagnostic Medicine at the University of Texas at Austin Dell Medical School. “There is also controversy as to how aggressively one should treat high blood pressure in order to decrease secondary damage to the brain.”

Each participant received brain magnetic resonance imaging (MRI) at the beginning of the study and four years later. The scans measured white matter lesions deep in the brain that can occur naturally with age but that are thought to raise the risk of cognitive decline and dementia. The scans also measured total brain volume, which is linked to cognitive function.

Over four years of follow-up, the mean systolic blood pressure in the intensive treatment group was 14 mm Hg lower than that of the standard treatment group. Although white matter lesions increased in both groups, they increased more slowly in the intensive treatment group. However, those in the intensive treatment group lost more total brain volume than those in the standard treatment group, a potential negative in terms of cognitive risk.

Bryan noted that while it is possible that the slower increase in white matter lesions could offset the potential negative impact of lower brain volume on cognition, “that relationship is less well understood and needs more investigation.”

In the second study, researchers looked at data from the Atherosclerosis Risk in Communities study, which obtained blood pressure for 4,761 participants at five visits spread out over 24 years and included neurocognitive evaluations at visits 5 and 6. Compared with participants who maintained normal blood pressure throughout midlife and late-life, the risk of developing dementia was 49% greater in participants who had chronic hypertension during midlife (ages 54 to 63 years) and late-life. The risk of developing dementia was 62% higher in those who had chronic high blood pressure during midlife followed by late-life low blood pressure, which the researchers defined as 90/60 mm Hg or lower.

Most of the participants who had late-life low blood pressure were taking blood pressure medications, but that does not mean the medications were to blame, either for the low blood pressure or the increased dementia risk, said lead author Keenan A. Walker, Ph.D., an assistant professor of neurology at Johns Hopkins Medicine.

“Conditions like arterial stiffening can lead to late-life declines in blood pressure, especially diastolic blood pressure. It is unclear whether arterial stiffening is a driver of dementia risk, rather than low blood pressure itself. It’s also entirely possible that late-life drops in blood pressure could be caused by neurodegenerative changes, which themselves raise the risk for dementia,” Walker said.

Although the evidence points to an association between blood pressure and dementia risk, care should be individualized, Walker added.

“It’s likely that each person will have a different sweet spot in terms of the best blood pressure to maintain cognitive health,” he said.

Bryan said that patients with mental illness may need extra support in their efforts to maintain a healthy blood pressure. “Unfortunately, blood pressure control often becomes more difficult with increasing age, cognitive impairment, and mental illness,” Bryan said. “While optimal blood pressure control in those with mental illness may be more challenging, it is achievable and perhaps even more important for these patients.”

Both studies were funded by the National Institutes of Health. ■