Longitudinal Systolic Blood Pressure Characteristics and Integrity of White Matter Tracts in a Cohort of Very Old Black and White Adults

Hypertension and long-term exposure to higher systolic blood pressure (SBP) are risk factors for dementia and disability among older adults living in the community.1–3 Although the beneficial effects of antihypertensive treatments have been shown for major cardiovascular events,4 the effects of antihypertensive strategies to reduce the excess risk of dementia attributable to higher SBP have yielded mixed results.5–8 Moreover, several studies have shown lower blood pressure (BP), but not high BP, relates to cognitive impairment.9,10 The strongest evidence that lowering SBP can reduce cerebral small vessel disease is for selected cohorts of stroke patients or for adults aged 80 years who are otherwise without a remarkable cardiovascular history would have neuroprotective effects.7,8,11 We have limited knowledge of which SBP characteristics may be most detrimental to the central nervous system. Similarly, the brain areas and parenchyma that are most vulnerable to higher SBP in older age are not entirely identified. Although several cross-sectional studies of older adults report that higher SBP is associated with generalized white matter hyperintensities and gray matter atrophy,6,12–15 there are few longitudinal studies of repeated SBP measures combined with neuroimaging, and associations with specific brain networks are not consistent across reports.14–18 Longitudinal variations in SBP, in addition to higher absolute levels, are emerging as risk factors for brain structural abnormalities, but evidence is derived largely from studies of patients with clinically overt vascular conditions16,19,20 rather than older adults living in the community. Quantifying the associations between longitudinal measures of SBP and the spatial distribution of brain abnormalities can help understand the mechanisms underlying the effects of SBP on risk of dementia and disability. Careful characterization and estimates of these associations can also provide biomarkers of brain health to monitor the possible neuroprotective effects of SBP management. This knowledge could lend insight and help in designing intervention trials targeting very old adults, a topic that is especially timely in light of the growing number of adults surviving past age 80 years. We hypothesized that, if higher SBP is related to higher risk of dementia and disability, as prior works suggest, then that the harmful SBP-related effects on the central nervous system should be primarily localized in brain areas most related to memory and executive function—that is, medial temporal, prefronto-parietal, and basal ganglia. Because of their watershed vascularization, these areas are also most vulnerable to the perfusion changes and small vessel disease that accompany higher SBP.21 In this study, careful characterization of SBP and antihypertensive medications over 10 years were examined in relationship to neuroimaging markers of brain integrity at the macro- and microstructural level in multiple regions and tracts. The relationship between higher variability of SBP over time and neuroimaging markers was also explored using coefficient of variation and trajectories analyses.