While hypertension is a known risk factor for stroke, less is known about the association of late-life blood pressure (BP)—in particular change in BP— with brain disease, including the main underling pathology of stroke (brain infarcts). Additionally, brain infarcts are known to be common and often silent in aging (clinically undetected).Even when neuroimaging is conducted, infarcts may be missed, especially when small.

Few studies have examined BP and other common brain diseases in aging, such as Alzheimer’s disease (AD), and while suggestions of an association are present, these studies are largely limited to fluid-based surrogate biomarkers.

Despite the promise of emerging neuroimaging and biotechnological advances, research using direct assessWment of cerebrovascular and AD pathology remains necessary to examine the association of BP with two common pathologies of aging in the brain, some features of which can only be demonstrated by neuropathologic examination.


Assessing the Relationships

For a study published in Neurology, Zoe Arvanitakis, MD, MS, and colleagues at the Rush Alzheimer’s Disease Center in Chicago, examined the relationship of average systolic and diastolic BP, and changes in BP, over time with postmortem neuropathologic changes found at autopsy. The research team evaluated common brain pathologies of aging including cerebrovascular disease and neurodegenerative disease (AD).

The investigators used longitudinal data from nearly 1,300 older, community-dwelling women and men who were evaluated yearly, for an average of 8 years, as part of an ongoing epidemiologic research study. Using regression analyses, they examined associations of average and decline in late-life SBP, and separately in DBP, with neuropathology.

Among study participants (mean age at death, 88.6 years; 65% women), the mean standardized, person-specific SBP across the study was 134 mmHg, while the DBP was 71 mmHg. Odds of brain infarcts were increased for participants with a higher mean SBP. Specifically, participants with a 1 SD SBP above the mean (147 vs 134 mm Hg) had a 46% increased odds of having one or more infarcts, as well as an increased odds of gross infarcts (46%) and microinfarcts separately (36%).

Additionally, a more rapidly declining SBP over time (steeper slope of change) increased the odds of one or more infarcts. Mean DBP, not slope, was related to brain infarcts. AD pathology analyses showed an association of a higher mean SBP with higher number of tangles but not plaques or other pathology (Table). Changes in BP (slope) were not significantly related to AD pathology.

“Results with cerebrovascular outcomes showed that a higher late-life systolic BP, and separately diastolic BP, were each associated with more brain infarcts, both large and small,” says Dr. Arvanitakis. “We also found relations of BP with increased vessel pathology, including more severe atherosclerosis. Results for neurodegenerative outcomes showed that a higher average systolic BP over the years was associated with more tangle pathology, one of the hallmarks of Alzheimer’s disease. There was no association with neuritic plaques.”

In addition to controlling for age in all models, Dr. Arvanitakis and colleagues specifically examined for effect modification by age. They found that, in the total group, the effect of the mean SBP over time on infarcts (of any size) was decreased with an increasing age at death (significant interaction of age with mean SBP). By contrast, older age did not affect the analyses using slope of SBP, or mean and slope of DBP, on infarcts or AD pathology.

Further, the relationship of DBP to infarcts was weaker and less consistent when compared with that of SBP. An increase in SD from the mean DBP value (eg, from 71 to 79 mm Hg) was associated with a 28% increased odds of any infarct, but the slope in DBP was not associated with infarcts.

“These results add to our understanding of the relation of level and change in systolic and diastolic BP across a range of values with brain pathology in aging,” says Dr. Arvanitakis. “In addition to expanding our knowledge of how BP relates to cerebrovascular disease, we also found some evidence for a relation with Alzheimer’s disease pathology.”


Looking Ahead

Dr. Arvanitakis adds that more research is needed to examine how late-life BP increases brain pathology, and how BP may contribute to brain dysfunction, including cognitive impairment and dementia. Because BP changes with aging and disease, the potential role of age on the relationship of BP with neuropathology needs further evaluation, she adds.