The Effect Of Parkin Mutation Status On Cognitive Functioning In Eopd Patients With Long Disease Duration: The Core-Pd Study

Objective: To compare the cognitive performance carriers and non-carriers of parkin mutations with long disease duration. Background We and others have reported that early-onset Parkinson disease (EOPD) individuals who are parkin mutation carriers have similar neuropsychological performance to non-carriers; however, it is unknown whether the risk for cognitive impairment among carriers and non-carriers remains similar as the disease advances. Design/Methods: We recruited 1103 individuals through the CORE-PD study through 16 centers, of which 155 probands underwent detailed neuropsychological testing. Carriers of LRRK2 and GBA mutation were excluded. Participants were divided by disease duration (range 1-47 years) median split. Neuropsychological performance among participants with longer duration (>14years) was examined. Neuropsychological domains included psychomotor speed, attention, memory, visuospatial function, and executive function. Domain scores were compared for parkin heterozygotes (n=9), compound heterozygotes/homozygotes combined (n=17) and non-carriers (n=22). Linear regression models were applied to assess the association between parkin mutation status (independent variable) and domain scores (dependent), adjusted for age, education and age at onset (AAO). Models were repeated to compare: 1.) homozygotes/compound heterozygotes to non-carriers excluding heterozygotes, and 2.) all mutation carriers to non-carriers. Results: Parkin mutation status was associated with younger age (heterozyogtes=53.4years, homozygotes/compound heterozygotes=53.3years, non-carriers=61.4years, p=0.012) and younger AAO (heterozygotes=30.4, homozygotes/compound heterozygotes=27.4, non-carrier=40.2 p parkin homozygotes/compound heterozygotes mutation status was associated with better performance after adjustment for age, AAO and education for memory (p=0.029) and attention (p=0.004). When all parkin carriers were compared with non-carriers the differences were noted in the executive domain (p=0.013) as well as memory and attention. Conclusions: EOPD individuals with long disease duration who are parkin mutation carriers perform better on tests of memory, attention and executive functioning than non-carriers. Supported by: NS36630, ULI RR024156 (Karen Marder). Disclosure: Dr. Caccappolo has nothing to disclose. Dr. Alcalay has nothing to disclose. Dr. Marder has received personal compensation in an editorial capacity for Current Neuroscience. Dr. Marder has received research support from the NIH, Michael J. Fox Parkinson Disease Foundation, CHDI, and the Huntington9s Disease Society of America. Dr. Tang has nothing to disclose. Dr. Rosado has nothing to disclose. Dr. Mejia-Santana has nothing to disclose. Dr. Ruiz has nothing to disclose. Dr. Orbe-Reilly has nothing to disclose. Dr. Ross has nothing to disclose. Dr. Verbitsky has nothing to disclose. Dr. Kisselev has nothing to disclose. Dr. Louis has nothing to disclose. Dr. Colcher has nothing to disclose. Dr. Comella has received personal compensation for activities with Ipsen, Merz Pharma, Allergan, Inc., and NuPathe. Dr. Comella has received research support from Ipsen, Merz Pharma, Allergan, Inc., the National Institutes of Health, and the Dystonia Study Group. Dr. Siderowf has received personal compensation for activities with Teva Neuroscience, Supernus Pharmaceuticals, Schering-Plough, and Merck Serono. Dr. Siderowf has received research support from the NINDS, the Department of Health of the Commonwealth of Pennsylvania, and Avid Radiopharmaceuticals. Dr. Jennings has received personal compensation for activities with Lundbeck Research USA as a speaker. Dr. Nance has received research support from Medivation, Santhera, Juvantia, Neurosearch Sweden, Pfizer Inc, Neuraltus, Impax, and Schwarz Biosciences. Dr. Bressman has received license fee payments from Beth Israel/Mount Sinai/Athena. Dr. Scott has nothing to disclose. Dr. Tanner has received personal compensation for activities with Impax Pharmaceuticals, Allergan, Inc. & Genentech, Inc. as a consultant. Dr. Tanner has received research support from Michael J. Fox Foundation, Department of Defense, Parkinson9s Disease Foundation, Parkinson9s Institute, Unity Walk and Brin Foundation. Dr. Mickel has nothing to disclose. Dr. Waters has received personal compensation for activities with Boehringer Ingelheim Pharmaceuticals, Inc., Novartis, and Teva Neuroscience as a speaker. Dr. Fahn has received personal compensation for activities with Intec Pharma, Merz Pharma, Oxford Biomedica, RJG Foundation, IMPAX Pharmaceuticals, and Lundbeck as a consultant. Dr. Fahn has received personal compensation in an editorial capacity for Elsevier and Springer. Dr. Cote has nothing to disclose. Dr. Frucht has received personal compensation for activities with UCB Pharma. Dr. Ford has received personal compensation for activities with Novartis and Medtronic, Inc. Dr. Rezak has received personal compensation for activities with Medtronic, Teva, Novartis, Allergan, Smih-Klein, Boehringer-Ingleheim, and UBC as a speaker. Dr. Friedman has received personal compensation for activities with Teva Neuroscience, Boehringer Ingelheim Pharmaceuticals, Inc., Genzyme Corporation, Adix, Roche Diagnostics Corporation. Dr. Friedman has received research support from Teva Neuroscience, Merck & Co., Inc., EMD Serono, Schering-Plough Corporation, National Institutes of Health, Michael J. Fox Foundation, GE Healthcare and Acadia. Dr. Marsh has nothing to disclose. Dr. Hiner has received personal compensation for activities with Teva Neuroscience. Dr. Payami has nothing to disclose. Dr. Molho has received personal compensation for activities with Allergan, Teva, Merz, Ipsen, and Boehringer Ingelheim. Dr. Molho has received research support from Teva, Allergan, Merz, IPsen, Parkinson9s Study Group, and Huntington9s Study Group. Dr. Ottman has received personal compensation for activities with Ortho-McNeil Janssen Scientific Affairs, LLC. Dr. Clark has nothing to disclose.