Often the first and most debilitating symptom in Alzheimer's disease (AD) is difficulty in learning and retaining new information. AD patients are impaired on all tests of explicit memory (e.g., recall and recognition of events, facts, and, in the laboratory, study-fist materials). The memory failure is thought to reflect the combined effects of damage to limbic and to neocortical neural systems, but it has been difficult to know which specific aspects of AD memory failure are due to the limbic versus the neocortical lesions. The overall goal of the present proposal is to decompose the memory failure of AD into limbic versus neocortical memory system dysfunctions through two logical analyses. First, we plan to compare the performance of AD patients with that of patients with pure global amnesia (GA). The two groups are similar in that they both have limbic system damage, but dissimilar in that the GA patients have little or no neocortical damage. By this logic, differences in explicit memory failures between AD and GA patients may be attributed to the neocortical damage in AD. We also propose to study implicit memory, which is intact in GA and thought to reflect neocortical memory systems. AD patients are impaired on some measures of implicit memory but intact on others. Comparison of AD and GA patients on implicit memory tests ought to suggest which neocortical memory systems are functionally spared and which are compromised in early AD. Second, we propose to use a within-task logic of dissociation that has seldom been applied to the study of memory failure in AD. The within-task logic, in contrast to the more often used between-task logic, ought to reveal the functional natures of spared and compromised memory systems in AD. In a multi-institutional collaboration, we propose 9 experiments with 120 early-stage AD patients, 20 CA patients, and 140 control subjects that test 5 hypotheses: (1) AD patients are impaired on both recollection-based and familiarity-based components of explicit memory; (2) GA patients are impaired on the recollection-based component of explicit memory but they are intact on the familiarity-based component of explicit memory; (3) AD and GA patients base a disproportionate amount of explicit recognition memory judgment on partially (AD) or fully (GA) preserved familiarity in the near absence of recollection; (4) AD patients have a specific deficit in conceptual implicit memory processes, with perceptual implicit memory processes remaining intact; and (5) AD patients have a specific deficit in retrieval-demanding tests of implicit memory, with identification-demanding tests of implicit memory remaining intact. The development of neural-system specific memory tests ought to be of particular value in the construction of biologically valid measures of cognition for studies examining putative treatments for AD and for other neurological diseases that affect learning as well as more benign processes, such as healthy aging, in which some aspects of memory often decline.
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