Dementia Risk Tied to Blood Pressure Fluctuations

Higher systolic blood pressure variability (BPV) over time raised dementia risk later in life, an observational study showed.

At 3, 6, 9, and 12 years, higher systolic BPV was tied to a higher subsequent risk of dementia, with HRs ranging from 1.02 (95% CI 1.01-1.04) to 1.10 (95% CI 1.05-1.16), reported Simin Mahinrad, MD, PhD, of Northwestern University’s Feinberg School of Medicine in Chicago, and co-authors.

The relationship between systolic BPV and dementia risk was stronger in people not taking calcium channel blockers (P for interaction <0.05), the researchers noted in Alzheimer’s & Dementia.

“Research tells us that elevated blood pressure in midlife has been associated with increased risk of cognitive decline as we age, and possibly with dementia,” said Heather Snyder, PhD, of the Alzheimer’s Association, who wasn’t involved with the study.

“Studies to date have produced mixed results regarding the impact of anti-hypertensive treatments on the underlying biology of Alzheimer’s or other dementia and cognitive decline, and whether the treatments can have an impact on disease risk or progression,” Snyder told MedPage Today. “It may be that cardiovascular-related interventions are specific to population or timing of the intervention.”

“Increasingly, studies are looking more broadly at interventions that address blood pressure — and less about the specific intervention — to determine their impact on cognitive decline and dementia,” she added.

One example is the Sprint MIND clinical trial. “In this study, aggressive treatment of systolic blood pressure resulted in nearly 20% fewer individuals progressing from healthy cognition to mild cognitive impairment,” Snyder said. “The study is ongoing and will evaluate the impact of a variety of interventions on progression to mild cognitive impairment and dementia.”

Independently of average blood pressure levels, BPV is emerging as a risk factor for dementia and Alzheimer’s disease in older adults. Evidence has suggested elevated BPV over both the longer term (visit-to-visit BPV) and shorter term (over minutes or days) is associated with cognitive decline and dementia.

“However, the majority of these prior studies did not censor dementia cases that developed during the BPV measurement period, raising concerns about reverse causation bias,” Mahinrad and co-authors pointed out. “Furthermore, these studies assessed BPV during periods spanning up to 6 years, while the effect of more prolonged exposure to BP fluctuations on dementia risk had not been explored.”

Mahinrad and colleagues evaluated long-term, visit-to-visit BPV in two ongoing cohorts of community-dwelling older adults: the Rush Memory and Aging Project (MAP) and the Religious Orders Study (ROS). Both are prospective studies enrolling older adults without known dementia who agreed to annual clinical evaluation and brain autopsy at death.

Blood pressure was measured with a sphygmomanometer by a trained research assistant at each annual visit. Visit-to-visit BPV was quantified over 3, 6, 9, and 12 years. Cognitive status was determined at every annual visit.

The researchers evaluated 2,234 participants who entered the study at age 65 or older. Most (74%) were women, and 94% were white. A total of 1,371 people were taking anti-hypertensive medications, including 466 people on calcium channel blockers.

Mean systolic BP over the first 3, 6, 9, and 12 years was 134, 133, 132, and 131 mm Hg, respectively. Mean systolic BPV was 8.3%, 9.2%, 10%, and 10%, respectively.

During a median follow-up of 10 years, 668 participants developed dementia, including 641 cases classified as Alzheimer’s disease. After full adjustment, systolic BPV of 10% or more was associated with an increased risk of dementia, and the highest HRs for systolic BPV were over 12 years (HR 1.75, 95% CI 1.16-2.66). Each unit increase in systolic BPV over 3, 6, 9, and 12 years was associated with 1.02-, 1.04-, 1.06-, and 1.10-fold increased risk of dementia (P<0.05).

The researchers observed a significant moderating effect of calcium channel blockers on the relationship between systolic BPV and dementia risk. “Specifically, the period-specific association between systolic BPV and dementia risk was stronger among those who were not taking calcium channel blockers during the first 3 or 9 years,” they wrote. “Adjustment for use of other anti-hypertensive medications (β-blockers, RAS [renin-angiotensin system] modulators, and diuretics) did not change the results.”

The study had several limitations, Mahinrad and co-authors noted. The sample primarily consisted of older white adults, and results may not apply to other groups. In addition, visit-to-visit BPV was measured annually; the effect of shorter variations in BP was not assessed.