Association of Long-Term Blood Pressure Variability with Cerebral Amyloid Angiopathy-related Brain Injury and Cognitive Decline

IntroductionLong-term systolic blood pressure variability (BPV) has been proposed as a novel risk factor for dementia, but the underlying mechanisms are largely unknown. We aimed to investigate the association between long-term blood pressure variability (BPV), brain injury, and cognitive decline in patients with mild cognitive symptoms and cerebral amyloid angiopathy (CAA), a well-characterized small-vessel disease that causes cognitive decline in older adults. MethodsUsing a prospective memory clinic cohort, we enrolled 102 participants, of whom 52 with probable CAA. All underwent a 3-tesla research MRI at baseline and annual neuropsychological evaluation over 2 years, for which standardized z-scores for four cognitive domains were calculated. BPV was assessed using a coefficient of variation derived from serial outpatient BP measurements (median 12) over five years. We measured the peak width of skeletonized mean diffusivity (PSMD) as a marker of white matter integrity, and other neuroimaging markers of CAA, including lacunes and cortical cerebral microinfarcts. Using regression models, we evaluated the association of BPV with microstructural brain injury and whether CAA modified this association. We also examined the association of BPV with subsequent cognitive decline. ResultsSystolic BPV was dose-dependently associated with PSMD (estimate=0.22, 95% CI: 0.06, 0.39, p=0.010), independent of age, sex, mean BP, common vascular risk factors, brain atrophy, and CAA severity. The presence of probable CAA strengthened the association between BPV and PSMD (estimate=9.33, 95% CI: 1.32, 17.34, p for interaction = 0.023). Higher BPV correlated with greater ischemic injury (lobar lacunes and cortical cerebral microinfarcts) and a decline in global cognition and processing speed (estimate=-0.30, 95% CI: -0.55, -0.04, p=0.022). DiscussionLong-term BPV has a dose-dependent association with alterations in white matter integrity, lobar lacunes, and cortical cerebral microinfarcts, and predicts cognitive decline. Controlling BPV is a potential strategic approach to prevent cognitive decline, especially in early-stage CAA. "TAKE-HOME POINTS" FOR SOCIAL MEDIAO_LITwitter handle: @LSveikata C_LIO_LIWhat is the current knowledge on the topic? Long-term blood pressure variability (BPV) has been proposed as a novel risk factor for dementia, but the underlying mechanisms are largely unknown. Brains affected by cerebral amyloid angiopathy (CAA), a well-characterized small-vessel disease, may be at risk of developing BPV-related brain injury. C_LIO_LIWhat question did this study address? Is long-term blood pressure variability (BPV) associated with brain injury and cognitive decline in patients with cerebral amyloid angiopathy (CAA)? C_LIO_LIWhat does this study add to our knowledge? This prospective memory clinic cohort study demonstrated a dose-dependent relationship between systolic BPV and altered white matter integrity, independent of demographic and vascular risk factors and more pronounced in individuals with evidence of CAA. Higher BPV was also associated with greater ischemic brain injury and cognitive decline. C_LIO_LIHow might this potentially impact on the practice of neurology? These findings suggest that BPV may be a modifiable risk factor for brain injury and cognitive decline, particularly in individuals with CAA, and could be targeted in preventative strategies. C_LI