DEVELOPMENT OF THE NON-DECLARATIVE MEMORY PRIMING DEFICIT OVER THE COURSE OF ALZHEIMER’S DISEASE

Abstract

Word-stem completion priming is a form of non-declarative memory that is impaired in patients with Alzheimer's disease (AD) but not in patients with circumscribed amnesia due to hippocampal damage. It may, therefore, have theoretical and diagnostic importance related to neocortical network deterioration in AD. However, little is known about the development of the priming deficit over the course of AD (e.g., is it an early or late feature?). To address this question, we cross-sectionally examined priming performance at different time points prior to death in individuals with autopsy-confirmed AD. 54 individuals with autopsy-confirmed AD had been tested on a word-stem completion priming test, and several other cognitive tests, .10 to 26.3 years prior to death. In the priming task, subjects were first exposed to 10 target words (e.g., MOTEL, ABSTAIN) and asked to rate each word in terms of its “likability.” Following two presentations and ratings of the list, subjects were shown three-letter stems (e.g., MOT, ABS) of words that were and were not on the target list and asked to complete them with the “first word that comes to mind.” Half of the stems could be completed with previously presented words, while the other half allowed assessment of baseline guessing rates. There was a significant association, best described as a quadratic function, between word-stem completion priming score (i.e., difference between target completion and baseline guessing rates) and the interval between testing and death (R2=.29; p<.001), even after controlling for final level of plaque (partial r=.49; p<.001) and tangle (partial r=.51; p<.001) pathology. Priming ability declined steadily until approximately 12 years prior to death and then flattened out at an impaired level until time of death. Systematic decline in word-stem completion priming ability may begin more than 20 years prior to death in individuals with AD. Thus, the word-stem completion priming test could be an early neurocognitive marker of the disease. Although the neurobiological basis of the priming deficit in AD remains unknown, the results may reflect an early decline in network associations between lexical, semantic and word-form information processing that occurs in distinct neocortical regions.