Background: Long-term blood pressure variability (BPV) has been proposed as a potential risk factor for dementia and cerebral small vessel disease progression. In this study, we investigate the association between BPV, brain injury, and cognitive decline in probable cerebral amyloid angiopathy (CAA).

Methods: Using a prospective memory clinic cohort, we enrolled 102 participants, including 52 with probable CAA and mild cognitive symptoms. BPV was assessed using a coefficient of variation derived from outpatient BP measurements (median 12) over 5 years before imaging with 3-tesla research magnetic resonance imaging. We measured peak width of skeletonized mean diffusivity and neuroimaging markers of CAA, including lacunes and cortical cerebral microinfarcts. Using regression models, we evaluated the association of BPV with white matter integrity and whether CAA modified this association. We also examined the association of BPV with longitudinal cognitive decline.

Results: Systolic BPV had a dose-dependent association with peak width of skeletonized mean diffusivity (standardized β=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 peak width of skeletonized mean diffusivity (β=9.33, 95% CI: 1.32-17.34, P for interaction=0.023). Higher BPV correlated with the presence of lobar lacunes, cortical cerebral microinfarcts, and a decline in global cognition and processing speed.

Conclusions: Long-term BPV had a dose-dependent association with altered white matter integrity, ischemic brain injury, and cognitive decline. Controlling BPV might be a potential novel therapeutic target to prevent cognitive decline in memory clinic patients with probable CAA and mild cognitive symptoms.