DUET-AD: Dual-task Evaluation Tool for early Alzheimer’s Disease.
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Project Summary. Alzheimer's disease (AD) is a major public health burden in the United States as it is the 5th leading cause of death in the United States, resulting in $305 billion in treatment costs in 2020, a number expected to triple by 2060. People with amnestic mild cognitive impairment (aMCI) are much more likely to develop AD, and the AD-related decline in cognition has a direct relationship with motor impairments, such as an increased risk of falling, which results in more significant healthcare costs. Improved early detection of AD is paramount to intervene before the degeneration of neurons, the point at which recent clinical trial interventions have shown little to no effect. Early support indicates that cognitive-motor dual-tasks (CMDT) may have promise for detecting AD pathophysiological changes even before a clinical diagnosis of AD, such as accumulation of amyloid beta (Aβ) plaques. Current CMDTs provided mixed results in the ability to identify aMCI and AD amongst other subtypes of MCI and dementia. This proposal will use a game-like, lower- extremity visuomotor CMDT (vCMDT) to explore performance as an indicator of cognitive status and AD- associated fluid biomarkers. A visuomotor task may be an ideal motor indicator of early AD because visuomotor tasks increase the demand on the posterior parietal cortex (PPC), a pivotal node in the more extensive fronto-parietal network that demonstrates structural changes and accumulates Aβ plaques in early AD. The central hypothesis is that greater vCMDT error will differentiate cognitive states of unimpaired (CU), non-aMCI, and aMCI, a population that has a high likelihood of developing AD. Further, we hypothesize the differences in vCMDT performance will be related to AD biomarker positivity, a method of assessing AD-risk growing in accessibility. Such a tool would allow for simultaneous assessment of biological and clinical risk for AD. This proposal will leverage the rich resources from the Vanderbilt Memory and Alzheimer’s Center (VMAC), including well-characterized Clinical Core participants from the Vanderbilt exploratory Alzheimer’s Disease Research Center. We will use our database and community outreach to recruit individuals who are CU and have aMCI and naMCI. Our multi-disciplinary team is ideally positioned to answer the proposed research questions through the aims of determining the difference in vCMDT performance between CU and different subtypes of MCI (Aim 1) and the association between vCMDT performance with fluid biomarkers of AD pathology (Aim 2). This work will provide a foundation for future R01 applications to refine the diagnostic and prognostic ability of a visuomotor dual-task challenge as a predictor of preclinical Alzheimer’s disease and understand the mechanistic underpinnings of dual cognitive and motor decline using a longitudinal study design. This study may also inform targets for interventions involving altered motor function. Such interventions may slow or halt the progression of more significant cognitive-motor deficits that may lead to eventual burdensome loss of ability to perform activities of daily living.
