Journal of the International Neuropsychological Society

Research Articles

Neuropsychological Profile of Parkin Mutation Carriers with and without Parkinson Disease: The CORE-PD Study

Elise Caccappoloa1a2, Roy N. Alcalaya1, Helen Mejia-Santanaa1, Ming-X. Tanga1a2, Brian Rakitina1a2, Llency Rosadoa1, Elan D. Louisa1a2a3a4, Cynthia L. Comellaa5, Amy Colchera6, Danna Jenningsa7, Martha A. Nancea8, Susan Bressmana9a10, William K. Scotta11, Caroline M. Tannera12, Susan F. Mickela13, Howard F. Andrewsa14, Cheryl Watersa1, Stanley Fahna1, Lucien J. Cotea3, Steven Fruchta1, Blair Forda1, Michael Rezaka15a16, Kevin Novaka15a16, Joseph H. Friedmana17a18, Ronald F. Pfeiffera19, Laura Marsha20a21a22, Brad Hinera23, Andrew D. Siderowfa24, Barbara M. Rossa2, Miguel Verbitskya2, Sergey Kisseleva2, Ruth Ottmana1a3a4a25, Lorraine N. Clarka2a26 and Karen S. Mardera1a2a3a27 c1

a1 Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York

a2 Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York

a3 Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, New York

a4 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York

a5 Department of Neurology/Movement Disorder Section, Chicago, Illinois

a6 Parkinson's Disease and Movement Disorders Center, Pennsylvania Hospital, Philadelphia, Pennsylvania

a7 The Institute for Neurodegenerative Disorders, New Haven, Connecticut

a8 Struthers Parkinson's Center, Park Nicollet Clinic, Golden Valley, Minnesota

a9 The Alan and Barbara Mirken Department of Neurology, Beth Israel Medical Center, New York, New York

a10 Department of Neurology, Albert Einstein College of Medicine, Bronx, New York

a11 Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, Florida

a12 Parkinson's Institute, Sunnyvale, California

a13 Marshfield Clinic, Department of Neurology, Marshfield, Wisconsin

a14 New York State Psychiatric Institute, Data Coordinating Center, New York, New York

a15 Department of Neurology, at North Shore University Health System, Evanston, Illinois

a16 Department of Neurology, at Northwestern University, Feinberg School of Medicine, Chicago, Illinois

a17 Parkinson's Disease and Movement Disorders Center of NeuroHealth, Warwick, Rhode Island

a18 Department of Clinical Neurosciences, The Warren Alpert School of Medicine of Brown University, Providence, Rhode Island

a19 Department of Neurology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee

a20 Morris K. Udall Parkinson's Disease Research Center of Excellence, Johns Hopkins University School of Medicine, Baltimore, Maryland

a21 Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine, Baltimore, Maryland

a22 Department of Neurology and Neurological Sciences Johns Hopkins University School of Medicine, Baltimore, Maryland

a23 Medical College of Wisconsin, Milwaukee, Wisconsin

a24 Department of Neurology, University of Pennsylvania Health System, Philadelphia, Pennsylvania

a25 Division of Epidemiology, New York State Psychiatric Institute, New York, NY

a26 Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York

a27 Department of Psychiatry, Columbia University Medical Center, New York, New York

Abstract

The cognitive profile of early onset Parkinson’s disease (EOPD) has not been clearly defined. Mutations in the parkin gene are the most common genetic risk factor for EOPD and may offer information about the neuropsychological pattern of performance in both symptomatic and asymptomatic mutation carriers. EOPD probands and their first-degree relatives who did not have Parkinson’s disease (PD) were genotyped for mutations in the parkin gene and administered a comprehensive neuropsychological battery. Performance was compared between EOPD probands with (N = 43) and without (N = 52) parkin mutations. The same neuropsychological battery was administered to 217 first-degree relatives to assess neuropsychological function in individuals who carry parkin mutations but do not have PD. No significant differences in neuropsychological test performance were found between parkin carrier and noncarrier probands. Performance also did not differ between EOPD noncarriers and carrier subgroups (i.e., heterozygotes, compound heterozygotes/homozygotes). Similarly, no differences were found among unaffected family members across genotypes. Mean neuropsychological test performance was within normal range in all probands and relatives. Carriers of parkin mutations, whether or not they have PD, do not perform differently on neuropsychological measures as compared to noncarriers. The cognitive functioning of parkin carriers over time warrants further study. (JINS, 2011, 17, 1–10)

(Received February 20 2010)

(Revised September 03 2010)

(Accepted September 07 2010)

(Online publication November 24 2010)

Correspondence:

c1 Correspondence and reprint request to: Karen Marder, MD, MPH, 630 W 168th St., Unit 16, New York New York 10032. E-mail: ksm1@columbia.edu

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