[P‐151]: Associative and item memory as outcome measures for Alzheimer's disease clinical trials: A pilot study

There is increasing evidence that episodic memory involves two separable processes, and that these processes may depend on different neuroanatomical and neurophysiological systems. Currently, clinical trials of medications to improve memory in patients with Alzheimer's disease (AD) are unable to measure these separable memory processes. One method of investigating such processes is to compare memory for the association between two items (associative memory) with memory for the items themselves (item memory). We have previously investigated associative and item memory in patients with AD and found that while both were impaired relative to healthy older adult controls, associative memory was more impaired than item memory. In this pilot study we have used an experimental memory test that allows for measurement of associative and item memory as an outcome measure in a randomized, double-blind, placebo controlled drug trial in patients with AD. Four equivalent stimulus sets were developed and used at six-week intervals throughout the trial. Subjects studied pairs of unrelated words on a notebook computer and were later asked to distinguish between these same studied pairs (intact) and new pairs that contained either rearranged studied words (rearranged) or nonstudied words (nonstudied). Intact minus nonstudied pairs provided an index of item memory, and intact minus rearranged pairs provided an index of associative memory. In this study we have demonstrated that using such a test is feasible within the setting of a clinical trial. Because medications to improve cognition in AD may preferentially improve associative or item memory, using this type of memory test may allow more sensitive detection of drug effects than standard memory tests.