Molecular Layer Atrophy Mediates the Association of Cumulative Blood Pressure Exposure With Cognitive Decline

High blood pressure (BP) is a known risk factor for cognitive decline and dementia, but the underlying mechanisms are largely unknown. We investigated the associations of cumulative BP exposure with hippocampal subfield volume and cognitive function and determined whether hippocampal subfield atrophy mediates the association between cumulative BP exposure and cognitive decline.

Between December 2020 and March 2023, participants were prospectively included from the Kailuan study. The cumulative BP was calculated as the area under the curve (mm Hg×years) using measurements from 2006 to 2023. A brain magnetic resonance imaging and the Montreal Cognitive Assessment was conducted beginning in 2020. The hippocampus was automatically segmented into 12 subfields via FreeSurfer 7.4.1 software (http://surfer.nmr.mgh.harvard.edu/).

A total of 1035 participants were included in this study. Increased cumulative systolic BP was associated with decreased volumes in the parasubiculum, presubiculum, subiculum, CA4, dentate gyrus, and molecular layer, and higher cumulative diastolic BP was associated with a lower volume in the presubiculum. Higher cumulative systolic BP and diastolic BP were associated with lower Montreal Cognitive Assessment scores. Decreased volumes in the subiculum; cornu ammonis (CA) 1, 2-3, and 4; dentate gyrus; molecular layer; fimbria; and hippocampal tail were associated with lower Montreal Cognitive Assessment scores. The molecular layer volume mediated negative associations of cumulative systolic BP and diastolic BP exposure with Montreal Cognitive Assessment scores, with mediating effect proportions of 5.61% and 8.68%, respectively.

Increased cumulative BP was associated with hippocampal subfield atrophy and cognitive decline, and the molecular layer volume mediated the negative association between cumulative BP and cognitive decline.