The majority of studies of cognitive aging focus on memory decline and Alzheimer's disease (AD). However, the preclinical stage of AD and other dementias may also begin with impairment in non-memory cognitive domains. We have preliminary clinical and neuropathological data suggesting that isolated executive impairment, a non-memory cognitive deficit, may be a risk for the development of functional decline and/or dementia. The overall goal of this project is to test the hypothesis that an isolated impairment of frontalexecutive function in non-demented elderly will predict future cognitive decline / dementia, functional impairment, and brain atrophy. To test this hypothesis, we will obtain longitudinal cognitive, functional, and neuroimaging measurements of 48 elderly subjects with isolated executive impairment and compare with 48 subjects with amnestic mild cognitive impairment (MCI) and matched controls. Specifically, we predict that lower baseline performance on tests of executive function will be associated with 1) lower performance on functional measures (i.e., activities of daily living) at two- and four-year follow-up intervals and 2) a decline in cognitive performance at two- and four-year follow-up intervals when compared with matched controls. We also hypothesize that subjects with isolated executive impairment will have a greater degree of prefrontal cortex atrophy on MRI at baseline and show a faster rate of prefrontal cortex atrophy at the two-year follow-up interval. Across all subjects, we predict that there will a relationship between scores on tests of executive function and the degree of frontal cortex atrophy. This project will increase awareness of non-memory cognitive impairment as a significant risk for functional and cognitive decline and/or dementia, 2) provide clinical and neuroimaging tools for the identification of individuals with non-memory cognitive impairment for possible inclusion in future primary prevention and treatment trials, and 3) expand differential diagnosis with individuals who present with isolated executive impairment to include AD in addition to frontotemporal dementia, vascular dementia, etc. ? ?
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