Many patients with mild Alzheimer's disease (AD) and the pre-Alzheimer's state of amnestic mild cognitive impairment (aMCI) live alone in the community. Memory dysfunction is the hallmark of AD and aMCI, and when their memory is sufficiently impaired, patients with these disorders will need to be provided with additional services, live with family, or move to an assisted living facility. Although memory dysfunction has been related with AD for over a century, the specific memory impairment observed in aMCI and mild AD has only recently been investigated. Building upon our prior work, the present proposal will systematically manipulate and evaluate different components of memory (e.g., familiarity, recollection, monitoring, source memory, the distinctiveness heuristic) that may be differentially affected by AD pathology. By understanding which components of memory are preferentially impaired, and which are relatively preserved, future interventions can be designed to help these patients live more independently.
Aim 1 will test the hypothesis that patients with aMCI and mild AD are over-reliant upon familiarity. Experiments 1 and 2 combine subjective reports, behavioral measures, and event-related potentials (ERPs) to understand the changes that occur in memory with a study-test delay (Expt. 1), or with several manipulations to alter the familiarity of items, includng fluency, repetition of items at various lags, and different exemplars of items (Expt. 2). Experiment 3 will attempt to lower familiarity-based false recognition and raise true recognition using deep encoding. Experiment 4 will examine whether metacognitive instructions can facilitate use of the distinctiveness of pictures to improve memory in a supermarket scenario.
Aim 2 will test the hypothesis that memory is impaired in patients with aMCI and mild AD in part due to their poor ability to monitor their responses. Experiment 5 manipulates the underlying ratio of studied to unstudied items at test and queries subjects regarding their perception of how many old and new items they have seen. Experiment 6 evaluates whether informing patients of the underlying ratio of studied versus unstudied items can reduce false recognition and improve overall memory when there are fewer studied than unstudied items.
Aim 3 will test the hypothesis that false memories of imagined activities in patients with aMCI and AD are increased by poor source memory and over- dependence upon familiarity, and reduced by conditions that diminish source memory confusion. Experiment 7 evaluates true and false memories of actions simply heard and not imagined. Experiment 8 evaluates whether warnings at study and test can reduce false memories associated with the imagined activities, thereby improving overall memory. Taken together, the laboratory findings generated from experiments in this proposal provide the necessary translational steps to develop strategies that may enhance memory and improve the lives of patients with aMCI and mild AD.

Public Health Relevance

Patients with Alzheimer's disease show progressive memory loss, impairing their function. The disease will develop in 5% to 11% of people over the age of 65, and it will affect as many as 50% of those over the age of 85. Amnestic mild cognitive impairment is the pre-Alzheimer's condition present when memory problems are just beginning, and it is also common, affecting up to 16% of those over the age of 65. Given these statistics, by 2013 it is estimated that there will be up to 1 million Veterans with Alzheimer's disease and up to 1.5 million with amnestic mild cognitive impairment. Because efforts to develop new medications to alter the course of Alzheimer's have not yet been successful, additional strategies are needed to improve the lives of those with the disorder. The studies in this proposal are an important step on the path toward developing these strategies to help patients with memory impairments live healthier, more independent lives.

National Institute of Health (NIH)
Veterans Affairs (VA)
Non-HHS Research Projects (I01)
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Mental Health and Behavioral Science B (MHBB)
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VA Boston Health Care System
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