High cognitive reserve mitigates the risk of dementia related to cardiometabolic diseases

Abstract

Introduction: Cardiometabolic diseases (CMDs) including type 2 diabetes, heart disease, and stroke have been linked to increased dementia risk. We examined whether high levels of cognitive (CR) can counteract the risk of dementia related to CMDs and explored the potential underlying mechanisms. Methods: Within the UK Biobank, 216,185 dementia-free participants aged ≥60 years were followed for up to 15 years to detect incident dementia cases. Dementia was identified through linkage to medical records. At baseline, each CMD was ascertained from medical records and self- reported medical history. Latent class analysis was used to generate an indicator of cognitive reserve (CR; low, moderate, and high) based on education, occupational attainment, confiding inothers, social connection, leisure activities, and television watching time. A subsample (n=13,664) underwent brain magnetic resonance imaging (MRI) scans 9 years after baseline. Volumes of total brain (TBV), white matter (WMV), gray matter (GMV), hippocampus (HV), and white matter hyperintensities (WMHV) were measured. Data were analyzed using Cox regression and linear regression. Results: At baseline, 43,403 (20.1%) participants had at least one CMD. There were 6,600 incident dementia cases over the follow-up (median 11.7 years [interquartile range 10.9-12.5 years]). In multi-adjusted Cox models, the hazard ratio (HR, 95% confidence interval) of dementia was 1.57 (1.48, 1.67) for participants with CMDs. In joint effect analysis, the HR of dementia was 2.13 (1.97, 2.30) for those with CMDs and low CR and 1.78 (1.66, 1.91) for those with CMDs and moderate to high CR (reference: CMD-free, moderate to high CR). In MRI data analysis, among people with CMDs, those with moderate to high CR had significantly higher TBV, GMV, WMV, and HV (p<0.001 for all) than those with low CR. Discussion: Moderate to high CR appears to mitigate the risk of dementia associated with CMDs by about one third. Lower levels of neurodegenerative and vascular pathologies might underlie this mitigating effect.