PROJECT SUMMARY/ABSTRACT
During the aging process there is a loss of automaticity in balance and mobility, where the engagement of
cortical resources for balance control may interfere with older adults’ ability to perform cognitive and balance
behaviors simultaneously. Over the course of normal aging, there is a decline in cerebral blood flow that is
linked to impaired cognitive function in older adults. However, it remains unknown whether age-related
declines in cerebrovascular and nervous system function may interact to manifest as cognitive interference in
balance control that precipitate falls and clinical dementia. Further, older adults who carry the Apolipoprotein
E4 (APOE4) allele, the greatest known genetic risk factor for Alzheimer’s disease, show greater
cerebrovascular dysfunction compared to age-matched noncarriers, and display worse balance performance
under cognitive loading conditions, supporting the potential effect of individual genotype on the link between
cerebrovascular health and balance control with aging.
Using electroencephalography (EEG) to measure dynamic cortical activity during standing balance reactions,
the candidate’s recent fellowship findings provide an individualized framework of cortical engagement
strategies for balance control in older adults that is associated with distinct aspects of balance behavior and fall
risk, including cognitive interference in balance performance. Currently, a major scientific barrier to the clinical
translation of this research is the lack of understanding of the factors that influence individual-specific cortical
strategies for balance control with aging. Emerging evidence suggests cognitive impairment with aging may be
caused by dysfunctional cerebral blood flow, specifically characterized by impaired cerebrovascular regulation
under conditions of physiologic stress. Blunted cerebral blood flow response to an acute bout aerobic exercise,
an assessment method pioneered by Dr. Billinger (primary mentor) and her laboratory, appears to be an early
indicator of dysfunctional cerebrovascular regulation in preclinical older adult populations. The proposed
project will be the first to test the link between cerebrovascular regulation during an acute bout of aerobic
exercise, measured as cerebral blood flow velocity using transcranial Doppler ultrasound, and cortical
function during balance behavior with aging, measured with cognitive dual-task balance performance (Aim
1) and EEG measures of cortical activity during balance reactions (Aim 2). An Exploratory Aim will test whether
genetic APOE4 carrier status alters the relationship between cerebrovascular regulation and balance control in
older adults. The scientific knowledge gained from these studies would create an individualized framework for
understanding cardiovascular-nervous system interactions that may contribute to balance disability in older
adults. This framework would provide a foundation for the development of precision-medicine strategies for fall
prevention, particularly in individuals at high risk for Alzheimer’s disease and subsequent falls.
