The determinants of healthy brain aging in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Abstract

Brain aging is highly heterogeneous. "SuperAgers" are an example of individuals over the age of 80 years who have memories as sharp as healthy people 20 to 30 decades younger. General changes that occur during the aging process in brain volume, cortical density, white matter and neurotransmitter systems can play a role in cognitive and psychiatric symptoms, which have a huge impact in global health of older people. However, it is unclear what determines the individual differences in brain aging. Main objective: To investigate determinants of healthy brain aging, defined as the absence of cerebrovascular and neurodegenerative disease, interrelating brain structures by Magnetic Resonance imaging (MRI), lifetime presence of cardiovascular risk factors, psychiatric symptoms, cognitive and functioning performance and social support. Additionally, we want to identify predictive markers of healthy brain aging, including genetic factors. In this context, the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil study), a large prospective cohort, presents high-quality and multidimensional data for the investigation of brain aging with more than 10 years of follow-up for clinical outcomes. Methods: An estimated sample of 1,393 subjects from the São Paulo center ELSA-Brasil will be invited to update their neuropsychiatric status (cognition, depression and mood disorders), sleep patterns, cardiovascular (CV), functional status, as well as, frailty evaluation. At same time, it will be performed a 3T MRI. Besides, a smaller sample of 296 participants: 148 individuals classified as SuperAgers (70 years or older at 2021 with cognitive global score higher than P85%) and its controls matched by sex (70 years or older at 2021, cognitive global score P15%-P85%) will be submitted an extensive brain evaluation with 7T MR scan. An additional analysis of cerebral small vessel disease (CSVD) will be performed in an asymptomatic individual with moderate-high cardiovascular risk submitted to both 3T and 7T MR. All of these factors mentioned above and their relationship to the structural and functional neuroimaging pattern of MRI will be extensively investigated at baseline (cross-sectional analyses) and during the follow-up (longitudinal analyses). Additionally, some aspects of ageing such as cognition, influence of genetic factors and longevity will be assessed by machine learning technique, as well as, survival analysis, including all-cause and specific mortality (cardiovascular and dementia), according to the neuroimaging findings. (AU)