Association Between Pulse Pressure and Structural Brain Changes in Aging: A Systematic Review and Meta-Analysis of...

The aim of this study was to investigate the associations between pulse pressure (PP) and age-related structural brain changes including brain volumes, white matter hyperintensities (WMH), fractional anisotropy, silent brain lesions, microbleeds, cerebral blood flow and metabolism, and beta-amyloid accumulation.

Systematic review of PubMed (MEDLINE), Scopus, and Ovid Embase (from inception to January 2023) and references of included studies among adult populations was conducted. Findings were summarized narratively and by performing a fixed-effects meta-analysis. Publication bias was tested by a funnel plot and Egger's regression asymmetry test.

Forty-seven studies (7 longitudinal) were included (>20 000 participants). In cross-sectional studies, PP consistently positively associated with gray matter volume and white matter hyperintensities with pooled standardized regression coefficients of 0.02 (95% CI, 0.007-0.038) and 0.06 (95% CI, 0.021-0.093), SD increase in PP per 1 SD increase in gray matter volume and white matter hyperintensities, higher odds of having a silent brain lesions pooled odds ratio of 1.11 (95% CI, 1.03-1.20) for 1 SD increase in PP, and cortical beta-amyloid (pooled estimate not available). There was limited evidence of an association with hippocampal volume, fractional anisotropy and mean diffusivity, cerebral microbleeds, cerebral blood flow and velocity, and cerebral metabolism. Longitudinal studies reported a negative association between PP and change in hippocampal volume and positive association with cortical beta-amyloid accumulation, but inconsistent findings were reported for total brain volume and white matter hyperintensities. Longitudinal studies were not available for gray matter volume, fractional anisotropy, silent brain lesions, cerebral microbleeds, and metabolism. Meta-regression provided no evidence that mean study-level arterial pressure modified the relationship between PP and associated brain metric.

Cross-sectional studies suggest a significant positive association between PP to gray matter volume, WMH, silent brain lesions, and cortical beta-amyloid that warrants further investigation by sufficiently powered longitudinal studies.