Impact of life-course growth and cumulative burden of cardiovascular disease risk factors on mid-life cognition in the Vellore birth cohort

Introduction Mid-life cognitive function contributes to a wide range of health and social outcomes. However, there are knowledge gaps in understanding the associations of life-course growth and longitudinal cardiovascular disease (CVD) risk marker profile which are major determinants of mid-life cognition. Our study, therefore, aims to examine the relationships of size at birth, growth during infancy, childhood, and adolescence, and the cumulative burden of CVD risk factors during adulthood with mid-life cognitive performance (brain reserve and structure). Methods and analysis The study will include 1400 participants aged between 49 and 54 from the Vellore Birth Cohort (VBC). Exposures include data collected previously on serial growth measurements (height and weight) from birth to the age of 45 years, IQ measured using the Binet-Kamat battery in childhood, and CVD risk factor profile (blood pressure, plasma glucose, insulin concentrations, lipid profile), modifiable lifestyle characteristics (diet, physical activity, smoking, and alcohol use) and socio-economic status (SES) measured at mean ages 28, 41.5and 45 years. The NIMHANS Neuropsychology Battery (NNB) and Weschler Memory Scale III – Indian Edition (WMS) will be used to assess cognitive performance across multiple domains as outcomes. Anthropometry, modifiable lifestyle characteristics, and SES will be updated for the current study. A subset of 150 participants will undergo functional neuroimaging [fMRI] to quantify brain volume, white matter hyperintensities, and resting state functional connectivity. Conditional regression methods and latent trajectory models will be used to quantify changes in growth and adult cumulative CVD risk factor burden. Factor analysis will be used to reduce the dimensions of multi-domain cognitive battery tests. Ethics and dissemination The institutional ethics committees of CMC, Vellore, India, have approved the study. Findings will be shared through scientific meetings and peer-reviewed journal publications.