Patients with probable Alzheimer's disease (AD) have semantic memory difficulty. In the previous funding period, we demonstrated that this is due to several factors, including degraded knowledge of the features that contribute to concepts;and an impairment in the processes within semantic memory that use these features, such as categorization. We mapped these difficulties onto a large-scale neural network that supports semantic memory, including modality-specific association cortex where feature knowledge may be stored;and multimodal association cortex that helps support categorization. In this renewal, we propose new directions in our analysis of the cognitive and neural mechanisms that support semantic memory, and their impairment in AD. We also study amnestic Mild Cognitive Impairment (aMCI) because these patients have milder episodic memory difficulty and less hippocampal atrophy than AD.
Specific Aim 1 focuses on the role that encoding frequently co-occurring features, or feature-binding, plays in category learning. We examine feature-binding during the acquisition of geometric shape categories and natural categories that are unimodal or multimodal. We hypothesize that explicit category learning is limited in AD and aMCI due in part to difficulty with feature- binding, and structural and functional MRI studies will relate this deficit to the amount of hippocampal disease. However, feature-binding will be more successful in AD and aMCI under implicit conditions, and this will be related to a relatively preserved cortically-mediated mechanism in the temporal lobe for implicit perceptual and semantic memory. Much of this work will be guided by a mathematical/computational model of category learning.
In Specific Aim 2, we test the hypothesis that partially degraded knowledge of the features of familiar concepts also contributes to semantic memory difficulty in AD and aMCI. We will examine object concepts that vary in their reliance on a variety of visual-perceptual features. We will also assess the role of working memory and relational knowledge in the comprehension of action concepts that vary in their motor component. Imaging studies will relate these aspects of feature knowledge to visual and frontal association cortex. This work will improve our understanding of the cognitive and neural basis for semantic memory, lead to improved diagnostic accuracy in AD, and suggest several potential avenues for improving the quality of life in these patients.

Public Health Relevance

This project investigates the cognitive and neural basis for impaired semantic memory in Alzheimer's disease (AD). We continue our previous work by examining the role of cortical and hippocampal mechanisms that support feature-binding during categorization, and we assess degraded knowledge of object concepts and verb thematic matrix relations. This work will help facilitate communication in the day-to-day care of patients with AD, and advance our understanding of a fundamental aspect of cognition.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Cognition and Perception Study Section (CP)
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Silverberg, Nina B
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University of Pennsylvania
Schools of Medicine
United States
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