Cardiometabolic disease, cognitive decline, and structural brain differences in mid‐ and late‐life: a large population‐based cohort study

Abstract

AbstractBackgroundThe impact of cardiometabolic diseases (CMDs; including type 2 diabetes [T2D], heart disease [HD], and stroke) on cognitive trajectories and brain structural changes across the life course is unclear. We aimed to explore the association of patterns of co‐morbid CMDs with cognitive decline and structural brain MRI measures in mid‐ vs. late‐ life.MethodWithin the UK Biobank, 46,562 dementia‐free participants aged 40‐70 were followed for 9 years. Baseline CMDs were ascertained medical records. A battery of 5 cognitive tests was administered at baseline and follow‐up and used to derive global and domain‐specific cognitive function scores. A subsample (n = 39,353) underwent brain magnetic resonance imaging (MRI) scans at the follow‐up examination. Volumes of total brain, white matter, grey matter, hippocampus, and white matter hyperintensities (TBV, WMV, GMV, HV, and WMHV) were assessed. Data were analyzed using multivariate adjusted mixed‐effects models and linear regression.ResultAt baseline, 3,437 (7.4%) participants had 1 CMD and 297 (0.6%) had ≥2. In mixed‐effects models, the presence of any CMD was related to a steeper decline in global cognitive function (β [95% confidence interval]: ‐0.005 [‐0.008, ‐0.003]) as well as working memory (‐0.024 [‐0.033, ‐0.014]), visual declarative memory (‐0.004 [‐0.007, ‐0.001]), and processing speed (‐0.002 [‐0.002, ‐0.001]), especially for those with CMD profiles involving T2D and/or HD. In stratified analysis by age (mid‐ [<60] vs. late‐ [≥60] life), CMDs were related to a decline in only processing speed in mid‐life, while in late‐life, CMDs were additionally related to a decline in verbal/numeric reasoning. In linear regression, people with CMDs had significantly lower TBV (‐0.15 [‐0.18, ‐0.12]), GMV (‐0.17 [‐0.20, ‐0.14]), WMV (‐0.11 [‐0.14, ‐0.08]), HV (‐0.14 [‐0.18, ‐0.11]) and significantly higher WMH (0.05 [0.02, 0.09]), and this was exacerbated among people with ≥2 CMDs compared to 1 CMD. Similar results were observed in both mid‐ and late‐life.ConclusionThe presence of CMDs is associated global/domain‐specific cognitive decline and brain MRI measures involving neurodegenerative and vascular markers in both mid‐ and late‐ life. Our findings highlight the need for the effective management of CMDs in mid‐life for the prevention of dementing disorders in late‐life.