Visit-to-visit blood pressure variability, brain MRI measures, and cognition in non-demented older adults

Blood pressure variability (BPV) may be a potentially modifiable risk factor for dementia. However, longitudinal studies investigating the associations between BPV, cerebrovascular disease (CeVD), and brain atrophy remain limited. Importantly, it is unclear whether these brain structural changes mediate the relationship between BPV and cognition, and whether such mediation effects are independent of preexisting brain pathology. This study included 362 non-demented individuals who underwent at least two neuropsychological assessments or brain magnetic resonance imaging (MRI). BPV was calculated as variation independent of mean. MRI markers of CeVD (i.e., white matter hyperintensity [WMH], lacunes, cerebral microbleeds [CMBs], intracranial stenosis, and cortical infarcts) and brain atrophy (i.e., white matter volume [WMV], gray matter volume [GMV], and lateral ventricular volume [VV]), were evaluated. Plasma p-tau181 was measured as a marker of amyloid pathology. Higher systolic BPV (SBPV) was associated with worse cognitive outcomes. SBPV was associated with WMH, cortical infarcts, and VV at the final brain MRI. These results were consistent in longitudinal analyses. The association between SBPV and cognition was partially mediated by CeVD and brain atrophy, with mediation proportion ranging from 17 to 24% for CeVD and 14 to 35% for brain atrophy. Preexisting CeVD and amyloid pathology had minimal influence on these mediation effects. SBPV showed stronger effects than other BPV indices on cognition, CeVD, and brain atrophy.