Functional decline in patients with mild cognitive impairment (MCI) is an important issue in dementia research. MCI has been defined primarily as a cognitive syndrome;diagnostic criteria stipulate that little or no impairment in Instrumental Activities of Daily Living (IADLs) be present. Yet MCI is also a dynamic transitional state between cognitive aging and dementia in which IADL decline clearly occurs and drives clinical judgments of conversion to AD and other dementias. Delineating the course of functional change in MCI remains essential for characterizing this construct and for scientific and clinical differentiation of cognitive aging, MCI and AD. The existing R01/R56 project (Functional Change in MCI) has systematically studied two key IADLs--medical decision-making capacity (MDC) and financial capacity (FC). These are "real world" activities that depend on integration of multiple component abilities and due to their complexity are vulnerable to the early cognitive declines found in MCI. Study findings to date have provided substantial new information regarding the nature, extent and rate of functional decline in MCI. These findings include: at baseline, patients with MCI already have significant deficits in MDC and FC relative to controls;initial measurable functional declines in FC and MDC occur over a 1 to 3 year period in MCI;significant declines in FC emerge in the year prior to MCI patient conversion to AD;following conversion to AD, functional decline in MCI accelerates;and FC is a strong predictor of both clinical progression and conversion to AD. Since our original application in 2004, the topic of MCI has undergone extensive scientific study and diagnostic revision. In addition, neuroimaging has emerged as a biomarker to identify patients with MCI progressing to AD. As a result, exciting new opportunities for investigating functional change in MCI now exist. One opportunity is to explicate the neuroanatomical basis of IADL decline in MCI. The field needs new models of IADL decline that integrate neural networks implicated in MCI and AD, and associated neuroanatomical (volumetric) and cognitive changes. A second opportunity concerns development of brief, performance based IADL measures sensitive to prodromal AD. For example, a brief, performance measure of FC sensitive to progression in MCI and conversion to AD would significantly advance clinical practice and research. This resubmission of our R01 competing renewal application pursues three related aims: -Aim 1 (Neuroimaging): To investigate longitudinally how MRI volumetric changes in cortical regions linked to the default mode network, and related cognitive changes, predict declining FC in patients with MCI -Aim 2 (Translational): To develop and validate a brief, performance based measure of FC sensitive to progression and conversion in prodromal AD -Aim 3 (Long Term Follow-Up): To conduct long-term follow-up of the existing study cohort to track progression and sequence of IADL decline in patients with MCI.
This proposed renewal project seeks to extend current work on functional change in patients with mild cognitive impairment (MCI). The existing project has shown that medical decision-making and financial abilities are impaired in patients with MCI as a result of early declines in cognitive abilities such as verbal memory and written arithmetic. This renewal project builds on these findings, and seeks to (1) understand how changes in brain volume and related cognitive deficits lead to impairments in financial abilities in patients with MCI, (2) develop a brief, readily usable, performance based instrument for detecting declining financial abilities in patients with MCI and AD, and (3) develop a more complete understanding of functional change over time in MCI by continuing follow-up of the existing study participants for another five years.
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