Age-Specific Incidence Rate For Dementia And Alzheimer’s Disease In NIA-LOAD/NCRAD and EFIGA Families (P2.148)

OBJECTIVE: To estimate age-specific incidence rate of dementia and Alzheimer9s Disease (AD) in large multiplex families BACKGROUND: The incidence rate of AD in large families is hypothesized to be higher than in the general population. We estimated age-specific incidence rates of dementia and LOAD in families recruited as a part of the NIA-LOAD/NCRAD study and Caribbean Hispanics in the EFIGA study. We also estimated the level of consanguinity in Caribbean Hispanics accounting for admixture in the population. DESIGN/METHODS: Restricting analyses to families with follow-up and complete phenotype information, 396 NIA-LOAD/NCRAD and 242 Caribbean Hispanic families were studied. Among the 943 at risk family members in the NIA-LOAD/NCRAD families, 126(13.4%) converted to dementia, of whom 109(86.5%) met criteria for LOAD. Among 683 at-risk family members in the Caribbean Hispanic families, 174 (25.3%) developed dementia, of whom 145 (83.3%) had LOAD. We estimated the amount of consanguinity in the Caribbean Hispanics by accounting for population admixture, using the algorithm implemented in REAP software. RESULTS: The annual incidence rates of dementia and LOAD in the NIA-LOAD/NCRAD families were 2.9% and 2.7% (65-74 years), 6.5% and 5.6% (75-84 years) and 7.9% and 7.1% (85 and above) respectively. Incidence rates in Caribbean Hispanic families were slightly higher 5.9% and 4.6% (65-74 years), 10.3% and 7.5% (75-84 years) and 10.1% and 7.2% (85 years and above). Contrasting the results here with the population-based estimates, the incidence was increased by three fold for NIA-LOAD/NCRAD families (Standardized Incidence Ratio=3.44) and was two-fold higher among the Caribbean Hispanic families compared to the NIA-LOAD/NCRAD families (SIR=1.70). The level of inbreeding in the Caribbean Hispanic subjects ranges from 0.018 (±0.04) to 0.002 (±0.018) which indicates excess sharing between unrelated subjects. CONCLUSIONS: : As hypothesized, the incidence rates for familial dementia and LOAD were significantly higher in than population based estimates. The higher incidence of disease could be due to enrichment of AD related variants due to high consanguinity in the Caribbean Hispanics Study Supported by: Disclosure: Dr. Vardarajan has nothing to disclose. Dr. Faber has nothing to disclose. Dr Bird has received licensing fee payments from Athena Diagnostics Inc. Dr. Bennett has received personal compensation for activities with Danone Inc., Dr. Wilmar Schwabe GmbH & Co., KG Pharmaceuticals, and Eli Lilly & Company. Dr. Bennett has received research support from Danone, Inc. Dr. Rosenberg has received personal compensation for activities with Janssen Pharmaceutica, and Novartis. Dr. Rosenberg has received personal compensation in an editorial capacity for the Journal of the American Medical Association, and the Journal of Neurological Sciences. Dr. Rosenberg has received license fee payments from Vitruvian Inc. Dr. Rosenberg has received research support from Janssen Pharmaceutica and Novartis. Dr. Boeve has received research support from Cephalon, Inc., Allon Therapeutics, and GE Healthcare. Dr. Graff-Radford has received personal compensation for activities with Codman as a member of a scientific advisory board. Dr. Graff-Radford has received personal compensation in an editorial capacity for The Neurologist. Dr. Graff-Radford has received research support from Janssen, Pfizer Inc., Medivation, Forest Laboratories Inc., and Allon. Dr. Goate has nothing to disclose. Dr. Farlow has received personal compensation for activities with Accera, Alltech, Avanir Pharmaceuticals, Eisai Inc., Helicon, Medavante, Medivation Inc., Merck & Co. Inc., Novartis, Pfizer Inc., Prana Biotech, Roche Diagnostics Corp., Sanofi-Aventis Pharmaceuticals Inc., Schering-Plough Corp., and Eli Lilly & Co. Dr. Farlow has received research support from Eli Lilly & Co., Novartis, Sanofi Aventis Pharmaceuticals, Inc., Roche Diagnostics Corporation, and Eisai Inc. Dr. Sweet has nothing to disclose. Dr. Lantigua has nothing to disclose. Dr. Medrano has nothing to disclose. Dr. Ottman has nothing to disclose. Dr. Schaid has nothing to disclose. Dr. Foroud has nothing to disclose. Dr. Mayeux has nothing to disclose.