Impaired Generalization Of Acquired Memory Pairings In Preclinical Familial Alzheimer'S Disease (Fad) Mutation Carriers

OBJECTIVE: To determine if generalization of memory pairings is affected in preclinical FAD. BACKGROUND: Generalization of arbitrary memory pairings is impaired in persons with medial temporal lobe damage. We hypothesized that this skill would be impaired early in the course of FAD due to fully-penetrant mutations. DESIGN/METHODS: 31 persons at-risk for inheriting FAD mutations underwent comprehensive evaluations including a lap-top based acquired equivalence task. During a training phase, subjects were implicitly trained on pairings between types of persons (e.g. male vs. female, child vs. adult) and fish of a specific color. Subjects learned the ways in which persons were associated with fish (e.g. females with blue fish, males with green fish) and were then trained on an examplar of a new pairing (a female child with a red fish as opposed to a purple fish). This was followed by a testing phase in which subjects were shown novel combinations (e.g. a female adult and red and purple fish) and were asked to choose the correct pairing (e.g. adult female and red fish). The number of errors was recorded and compared between mutation carriers (MCs) and non-carriers (NCs) using mixed ANOVAs. RESULTS: 22 subjects were FAD MCs and 9 were NCs. They did not differ with regard to age, gender, or MMSE score (mean score of MCs 29.2, range 25-30). 9 MCs had CDR scores of 0.5, suggesting mild impairment, and the rest were asymptomatic. MCs made significantly more errors on generalization trials during the testing phase than NCs (F(1,29) = 9.3, p = 0.005) though the interaction between group and type of trial was only marginally significant (F(1,29)= 2.9, p = 0.099). CONCLUSIONS: Generalization of arbitrary memory pairings tested using this acquired equivalence paradigm is impaired in medial temporal lobe damage, including in preclinical FAD mutation carriers. Supported by: Easton Consortium for Alzheimer9s Disease Drug Discovery and Biomarker Development, NIA K08 AG-22228, the Dominantly Inherited Alzheimer Network (DIAN, U01 AG032438), the UCLA Alzheimer9s Disease Research Center Grant (P50 AG16570), and the UCLA Clinical Translational Research Institute 1UL1-RR033176. Disclosure: Dr. Myers has nothing to disclose. Dr. Simon has nothing to disclose. Dr. Wharton has nothing to disclose. Dr. Medina has nothing to disclose. Dr. Alvarez-Retuerto has nothing to disclose. Dr. Coppola has nothing to disclose. Dr. Gluck has nothing to disclose. Dr. Ringman has received personal compensation for activities with Takeda Pharmaceuticals and StemCells, Inc. as an advisory board member. Dr. Ringman has received research support from Janssen, Pfizer Inc, Accera, Bristol-Myers Squibb, Inc., and Wyeth Pharmaceuticals.