Joint multi-omics profiling of brain and body health in aging

The human brain and peripheral systems undergo coordinated changes throughout the lifespan, yet studies of aging have traditionally examined these systems as separate entities. Here we ask how brain health relates to peripheral biomarkers of bodily health including body mass index, blood pressure, and blood biochemistry results. We use partial least squares analysis to identify generalizable patterns of covariance between multi-modal neuroimaging data (structural, functional, diffusion, and arterial spin labeling MRI), demographic, and peripheral physiological markers in two large-scale deeply phenotyped datasets: the Human Connectome Project-Aging and UK Biobank. This data-driven pattern learning approach identifies two principal axes of brain-body associations in both biological sex groups. The first axis is driven by the dominant contribution of age. Across multiple brain measures, aging is associated with loss of brain structural integrity and cerebral vascular dysfunction. The second axis is driven by metabolic features, characterized by low high-density lipoprotein cholesterol, elevated body mass index, blood pressure, glycosylated hemoglobin, insulin, glucose, and alanine aminotransferase, and reduced cerebral blood perfusion. Finally, we show that deviations from a healthy metabolic profile are linked to cognitive deficits, particularly in females. Our study contributes to development of comprehensive translatable biomarkers for brain health assessment, and highlights the importance of metabolic health as a determinant of brain health.