Longitudinal impact of midlife cerebrovascular pulsatility on brain tissue integrity and cognitive aging

PROJECT SUMMARY Normal aging is associated with a gradual decline in cognitive abilities across the lifespan, which is accelerated by midlife vascular risk factors, including stiffening of the large elastic arteries. The purpose of this project is to determine whether arterial stiffness is an early contributor to cognitive aging through the transmission of damaging pulsatile energy into the brain. Magnetic resonance elastography (MRE) is a non-invasive imaging modality that detects the viscoelastic properties of tissue and serves as a sensitive biomarker of brain tissue health and microstructural integrity. MRE has shown that brain tissue softening occurs with normal aging and likely precedes gross tissue atrophy. This 3-year longitudinal study seeks to determine the underlying mechanisms linking midlife vascular risk factors with the early loss of brain tissue structure and function. We will (1) determine the early mechanisms leading to age-related increases in cerebrovascular pulsatility, (2) determine whether changes in cerebrovascular pulsatility and brain tissue viscoelasticity are spatially and temporally correlated, and (3) determine whether cerebrovascular pulsatility mediates the loss of cognitive performance through the disruption of specific neuronal substrates important for memory performance (i.e., the hippocampus). Ultimately, this project will identify the earliest underlying mechanisms by which vascular aging contributes to the loss of brain tissue integrity and cognitive performance leading to new targets for interventions aimed at preventing age-related cognitive impairment.