Identifying causal and modifiable mechanisms of gait and falls in older adults is crucial for risk assessment and early interventions. Herein, we propose a three-level theory-driven approach integrating Clinical Neuropsychology, Cognitive Neurosciences, and Genetics to explore mechanisms of gait and falls in non- demented subjects age 70 and older residing in the community. We showed that clinical neuropsychological measures of attention and executive function were strongly related to gait and falls at cross-section. Herein, we propose to examine prospectively how specific clinical neuropsychological tests capturing the domains of Attention Executive function, Verbal IQ and Memory predict gait performance (aim 1 hypothesis a) and falls (aim 2 hypothesis a) in a large cohort of older adults residing in the community. We further propose a complementary neuroscience approach using the Attention Networks Test (ANT) to examine how empirically defined components of attention (alerting, orienting, executive attention) are related to gait (aim 1 hypothesis b) and falls (aim 2 hypothesis b). These sub-components of attention have been related to separate brain networks and thus can advance research toward identifying mechanism as opposed to correlates of gait and falls. Among the Dopaminergic genes, Catechol O-methyltransferase (COMT) has been most consistently related to attention and executive functions. In light of the association between COMT and executive control, which has been implicated in impaired gait and falls, a novel genetic link of cognitive control of human locomotion in aging may be identified. Herein, we will examine whether COMT polymorphisms are related directly or via cognitive control to gait (aim 1 hypothesis c) and falls (aim 2 hypothesis c). Our long-term goal is to identify specific cognitive and genetic mechanisms pertinent to developing more efficient risk assessment and intervention programs of decline in gait and falls in older adults. Significance: It is of vital public health importance to identify causal and modifiable factors of gait impairment and falls as a prelude towards formulating more effective assessments and interventions. We believe that this theory driven application will provide valuable insights into risk assessment, as well as rehabilitative and pharmacological interventions for individuals at risk of decline in gait and falls.
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