Trajectories and modifiable risk factors of brain, gait, and cognitive decline in aging and pre-dementia

PROJECT SUMMARY/ABSTRACT: Clinical gait abnormalities are present in about 35% of community-dwelling older adults in the US, and accelerated gait decline is associated with many adverse physical and cognitive outcomes - including falls, disability, cognitive decline, and dementia. Such outcomes not only reduces the quality of life of affected individuals, their families, and friends, but also leads to increased health care costs. In 2000 the direct costs of falls among older adults exceeded $19 billion, and the cost of health care following an emergency visit for an injurious fall among older adults totaled 6.8 billion in the US. In 2014, the estimated cost of formal care to people with Alzheimer's disease and related dementias was 214 billion in the US, plus another 220 billion in estimated costs for informal care provided by family members and other unpaid caregivers. Hence, a better understanding of trajectories, and modifiable risk factors, of brain, gait, and cognitive decline in aging can have a tremendous impact on individuals as well as to society. We aim to compare and contrast trajectories of functional and structural brain changes with gait decline and cognitive decline in cognitively-healthy older adults, and older adults in the early stages of cognitive decline. We hypothesize that functional and structural changes in the control pathway of human locomotion ? including supplementary motor, insular, and prefrontal cortex regions ? precede (or have earlier change points than) gait decline and cognitive decline (Hypothesis 1a), and that functional brain changes precede structural brain changes (Hypothesis 1b). We further hypothesize that functional and structural decline in these regions will be steeper or have earlier change points in older adults with the motoric cognitive risk (MCR) syndrome (Hypothesis 2) ? a pre-dementia syndrome characterized by slow gait and cognitive complaint ? as well as in older adults with few high-contact social relationships and poor social networks (Hypothesis 3). We will cross-enroll 200 LonGenity study participants with up to 10 years of annual gait and cognitive testing, and 2 planned MRI scans (3 years apart; 23 baseline MRIs completed). We propose to add a third MRI scan (3 years later) to permit examination of both linear and non-linear relationships, and to extend annual gait, cognitive and social network testing. This proposal is innovative because it simultaneously examines trajectories of both functional brain decline (task-based functional activation/deactivation, resting-state functional connectivity) and structural brain decline (gray matter volume, cortical thickness, structural connectivity), gait decline, and cognitive decline in older adults in general ? and as they relate to the MCR pre-dementia syndrome, and social networks in particular. This proposal has the potential to provide a better understanding of the interrelationships between gait, cognition and brain aging ? and inform the development of targeted, and appropriately sequenced, interventions for maintaining gait and cognition in aging, pre-dementia, early Alzheimer's disease and related dementias.