Association of early life cardiovascular risk factors with grey matter structure in young adults in the United Kingdom: the ALSPAC study.

Background: Cumulative exposures to obesity, hypertension, and physical inactivity from midlife (40-65 years) onwards are three known cardiovascular risk factors for dementia and associated cerebral structural damage. Exactly how early in the lifespan sensitive periods for exposure to these risk factors begin is yet to be established, specifically with respect to onset of cerebral structural changes. We aimed to investigate whether cardiovascular risk across childhood and adolescence is already associated with cerebral structure in regions previously linked with dementia, during young adulthood.

Methods: Participants were selected from the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK-based prospective cohort of young people, if they had participated in a neuroimaging sub-study (N = 862). We entered data from repeated clinical assessments into mixed-effects models to estimate baseline and rate of change in body mass index (BMI) and mean arterial pressure (MAP) between ages 7-17 years, and physical activity (PA) between 11-15 years. Linear models assessed whether cardiovascular risk factors were associated with grey matter macrostructural indices (cortical thickness, surface area, volume) in young adulthood (∼20 years).

Findings: BMI was found to be associated with grey matter macrostructure in nodes of Default Mode Network previously found to show atrophy in dementia. Baseline BMI was associated with thickness of precuneus cortex and entorhinal surface area, whilst rate of change in BMI across childhood and adolescence was associated with thickness of parahippocampal and middle temporal gyri and inferior parietal cortex in addition to entorhinal and parahippocampal surface area. Further, we identified associations between baseline MAP and PA and entorhinal surface area. Exploratory whole-brain analyses revealed associations between baseline and rate of change in these cardiovascular risk factors and the cortical thickness, surface area, and volume of broader groups of cortical and subcortical regions.

Interpretation: Findings provide preliminary evidence that cerebral structural differences in regions linked to dementia in old age may be legacy of developmental differences associated with cardiovascular risk exposure during early life. This has relevance for lifespan models of dementia risk and timing of preventative interventions. Further work is required to generalise findings beyond this predominantly white, male, and middle-class sample to more diverse cohorts.

Funding: NIHR Oxford Health BRC (NIHR203316), Wellcome Trust (203139/Z/16/Z).