Nearly 25% of Americans age 65+ report serious mobility problems. Mobility impairments decrease quality of life and predict increased risk of falls, disability, and mortality. However, the contribution of age-related brain changes to mobility impairments is not well understood. F99 work will examine how cortical inhibitory function relates to gait and balance declines with aging. K00 work will examine the same questions in mild cognitive impairment (MCI) and test exercise as an intervention to improve cortical inhibitory function. The sponsor's (Dr. Rachael Seidler) past work supports the novel hypothesis that declines in cortical inhibitory processes at least partially underlie motor impairments with aging.
For Aim 1 (F99), the candidate is collecting two measures of lower limb cortical inhibition in 30 young and 30 older adults: 1) gamma-aminobutyric acid (GABA)-edited magnetic resonance spectroscopy (MRS) and 2) transcranial magnetic stimulation-induced cortical silent period. GABA-edited MRS provides a measure of GABA neurotransmitter concentration, while cortical silent periods provide a measure of functional cortical inhibition during muscle activity. The F99 work addresses whether these two measures of cortical inhibition are reduced in older age (Aim 1a) and whether cortical inhibition relates to individual differences in gait (Aim 1b) and balance (Aim 1c). Mobility is often more impaired in MCI than in healthy aging. Motor symptoms typically arise much earlier than cognitive symptoms, and presence of motor symptoms relates to higher risk of Alzheimer's disease. Past work suggests that cortical inhibitory function is impaired in MCI and dementia, supporting that changes in cortical inhibition could be a component of MCI. Thus, for Aim 2 (K00), the candidate will work with Dr. Kirk Erickson to test whether cortical inhibition is reduced in MCI compared to healthy aging (Aim 2a) and if cortical inhibition relates to gait and balance in MCI (Aim 2b). Given relationships between cortical inhibition and motor control in healthy adults, it is feasible that cortical inhibition changes could also relate to mobility declines in MCI. Understanding neurotransmitter systems involved in mobility declines is important for development of interventions. Thus, the candidate will test whether aerobic exercise influences cortical inhibition in aging and MCI (Aim 2c). Past work demonstrated effects of exercise on cortical inhibition in young adults, but this has yet to be tested in aging or MCI. This work directly contributes to the NIA's major goals of preserving mobility in aging and studying brain changes with MCI. To successfully complete these aims, the candidate will receive extensive training from an expert mentorship team in biomechanics, brain imaging, brain stimulation, MCI, and exercise intervention work. This training will provide the candidate with a comprehensive toolkit to succeed as an aging researcher, with my future independent research program focused on: 1) determining the brain changes that contribute to motor declines in older age and MCI, and 2) identifying interventions to preserve motor function in older age and MCI.
Nearly a quarter of all Americans age 65+ report serious mobility problems, and mobility problems predict greater risk of dementia; thus, preserving mobility in older age is an NIA priority. Our past work suggests that the cortical inhibitory system contributes to motor declines with aging. This proposal will test if cortical inhibition relates to individual differences in walking and balance in older age (F99) and mild cognitive impairment (K00), and whether aerobic exercise affects cortical inhibition (K00). The findings from this work could lead to the development of novel interventions to preserve mobility and prevent disability in aging and mild cognitive impairment.
