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Late-life systolic and diastolic blood pressure were separately associated with the number of brain infarcts at autopsy, as was faster decline in systolic blood pressure over time, a large, prospective study found.

While the odds of gross infarct and microinfarct were higher in older adults who had higher average systolic blood pressure, a more rapidly declining systolic pressure slope over time increased the odds of one or more infarcts, reported Zoe Arvanitakis, MD, of the Rush Alzheimer's Disease Center at Rush University Medical Center in Chicago, and colleagues in .

"We also found a relationship between higher average systolic blood pressure and one of the key pathological markers of Alzheimer's pathology, neurofibrillary tangles," Arvanitakis told 番茄社区.

Hypertension is a risk factor for stroke, but less is known about the whole range of late-life blood pressure, particularly changes in blood pressure, Arvanitakis noted.

The researchers studied 1,288 people who had enrolled in one of three ongoing, prospective, community-based cohort studies: the , the , and the . They followed participants until death, which occurred an average of 8 years later at a mean age of 88.6. Each participant had blood pressure measured yearly and brain autopsy after death.

Two-thirds of participants had a history of high blood pressure and 87% used an antihypertensive medication. Two-thirds also had at least one vascular risk factor at baseline, and nearly a third had a vascular disease.

Averaged across the years of the study, systolic blood pressure was 134±13 mm Hg in the group, declining 0.8 mm Hg per year on average. Diastolic blood pressure was 71±8 mm Hg averaged across the years; it declined, on average, 0.1 mm Hg per year. Blood pressure decline was nonlinear, with half of it occurring in the last 6 years before death.

Neuropathology data showed that nearly half (48%) of participants had one or more chronic infarcts of any size or location. For an increase by 1 standard deviation in the standardized person-specific mean systolic blood pressure -- from 134 to 147 mm Hg, for example -- the researchers found 46% increased odds of gross infarct and 36% increase odds of microinfarct.

The slope of, but not the mean, systolic pressure was associated with cortical infarcts and the mean, but not the slope, was associated with subcortical infarcts. The relationship of diastolic blood pressure to infarcts was weaker and less consistent.

Average systolic blood pressure was tied to higher severity grades of atherosclerosis (OR 1.95, 95% CI 1.66-2.29). Both average (OR 1.36, 95% CI 1.16-1.59) and declining slope of (OR 1.43, 95% CI 1.10-1.84) diastolic pressure also were associated with higher atherosclerosis severity.

Small vessel pathology showed that average systolic pressure also was linked to higher severity grades of arteriolosclerosis (OR 1.23, 95% CI 1.05-1.43). There was no association of the slope of systolic pressure with arteriolosclerosis, and no significant association between diastolic pressure and arteriolosclerosis.

Higher mean systolic pressure also was associated with higher numbers of tau protein tangles (P=0.038), but not with other measures of Alzheimer's pathology, including plaques. This link is difficult to interpret and needs more investigation, Arvanitakis said.

This research "confirms hypertension is bad for the brain and adds to a growing number of studies showing decline in blood pressure may be also detrimental," noted Lidia Glodzik, MD, PhD, of New York University Langone Health in New York City, who was not involved in the study.

"It has been previously reported that low or declining blood pressure was related to cognitive deterioration and brain atrophy," she told 番茄社区. "Some postulated that reduction in blood pressure precedes dementia. However, it is still uncertain whether this reduction is just a corollary of frailty often associated with dementia or a causative factor."

The fact that decline in systolic blood pressure was associated with increased chance of having an infarct in this study "speaks, in my opinion, in favor of causality," she added. "One possibility explaining the connection between decline in blood pressure and brain infarcts is hypoperfusion. Cerebral blood flow in hypertension and hypotension is a relatively old, but still not fully explored, avenue of research."

Study limitations included no data on midlife blood pressure measurements, and no data about blood pressure from time points between annual evaluations. Most participants were on blood pressure medication, limiting the ability to study a wider distribution of values. And "further work is needed to identify at-risk subgroups and associated mechanisms by which mean and slope of blood pressure are associated with neuropathology," the authors wrote.

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