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Original Investigation |

Cognitive and Motor Function in Long-Duration PARKIN-Associated Parkinson Disease

Roy N. Alcalay, MD, MSc1,2; Elise Caccappolo, PhD1; Helen Mejia-Santana, MSc1; Ming Xin Tang, PhD1,2; Llency Rosado, MD1; Martha Orbe Reilly, MD1; Diana Ruiz, BSc1; Elan D. Louis, MD, MSc1,2,3,4; Cynthia L. Comella, MD5; Martha A. Nance, MD6; Susan B. Bressman, MD7,8; William K. Scott, PhD9; Caroline M. Tanner, MD, PhD10; Susan F. Mickel, MD11; Cheryl H. Waters, MD1; Stanley Fahn, MD1; Lucien J. Cote, MD1,3; Steven J. Frucht, MD1; Blair Ford, MD1; Michael Rezak, MD, PhD12; Kevin E. Novak, PhD13,14; Joseph H. Friedman, MD15,16; Ronald F. Pfeiffer, MD17; Laura Marsh, MD18; Bradley Hiner, MD19; Haydeh Payami, PhD20; Eric Molho, MD21; Stewart A. Factor, DO22; John G. Nutt, MD23; Carmen Serrano, MD24; Maritza Arroyo, MD24; Ruth Ottman, PhD1,3,4,25; Michael W. Pauciulo, MBA26; William C. Nichols, PhD26; Lorraine N. Clark, PhD2,27,28; Karen S. Marder, MD, MPH1,2,3,29
[+] Author Affiliations
1Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York
2Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York
3Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, New York
4Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York
5Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois
6Struthers Parkinson's Center, Park Nicollet Clinic, Golden Valley, Minnesota.
7The Alan and Barbara Mirken Department of Neurology, Beth Israel Medical Center, New York, New York
8Department of Neurology, Albert Einstein College of Medicine, Bronx, New York
9Dr John T. Macdonald Foundation, Department of Human Genetics, Miami Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, Florida
10Parkinson's Institute, Sunnyvale, and Department of Health Research and Policy, Stanford University, Palo Alto, California
11Marshfield Clinic, Department of Neurology, Marshfield, Wisconsin
12Central DuPage Hospital, Neurosciences Institute, Movement Disorders Center, Winfield, Illinois
13Department of Neurology, NorthShore University Health System, Evanston, Illinois
14Department of Neurology, University of Chicago, Pritzker School of Medicine, Chicago, Illinois
15Department of Neurology, Butler Hospital, Providence, Rhode Island
16Department of Neurology, Alpert Medical School, Brown University, Providence, Rhode Island
17Department of Neurology, College of Medicine, University of Tennessee Health Science Center, Memphis
18Morris K. Udall Parkinson's Disease Research Center of Excellence and Departments of Psychiatry and Behavioral Sciences and Neurology and Neurological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland
19Department of Neurology, Medical College of Wisconsin, Milwaukee
20New York State Department of Health Wadsworth Center, Albany, New York
21Parkinson's Disease and Movement Disorders Center of Albany Medical Center, Albany, New York
22Department of Neurology, Emory University, Atlanta, Georgia
23Portland VA Medical Center, Parkinson Disease Research, Education and Clinical Center, and Oregon Health and Science University, Portland
24Department of Neurology, University of Puerto Rico, San Juan
25Division of Epidemiology, New York State Psychiatric Institute, New York, New York
26Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, and Department of Pediatrics; University of Cincinnati College of Medicine, Ohio
27Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York
28Center for Human Genetics, College of Physicians and Surgeons, Columbia University, New York, New York
29Department of Psychiatry, Columbia University Medical Center, New York, New York
JAMA Neurol. 2014;71(1):62-67. doi:10.1001/jamaneurol.2013.4498.
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Importance  Data on the long-term cognitive outcomes of patients with PARKIN-associated Parkinson disease (PD) are unknown but may be useful when counseling these patients.

Objective  Among patients with early-onset PD of long duration, we assessed cognitive and motor performances, comparing homozygotes and compound heterozygotes who carry 2 PARKIN mutations with noncarriers.

Design, Setting, and Participants  Cross-sectional study of 44 participants at 17 different movement disorder centers who were in the Consortium on Risk for Early-Onset PD study with a duration of PD greater than the median duration (>14 years): 4 homozygotes and 17 compound heterozygotes (hereafter referred to as carriers) and 23 noncarriers.

Main Outcomes and Measures  Unified Parkinson Disease Rating Scale Part III (UPDRS-III) and Clinical Dementia Rating scores and neuropsychological performance. Linear regression models were applied to assess the association between PARKIN mutation status and cognitive domain scores and UPDRS-III scores. Models were adjusted for age, education, disease duration, language, and levodopa equivalent daily dose.

Results  Carriers had an earlier age at onset of PD (P < .001) and were younger (P = .004) at time of examination than noncarriers. They performed better than noncarriers on the Mini-Mental State Examination (P = .010) and were more likely to receive lower scores on the Clinical Dementia Rating (P = .003). In multivariate analyses, carriers performed better than noncarriers on the UPDRS-III (P = .02) and on tests of attention (P = .03), memory (P = .03), and visuospatial (P = .02) cognitive domains.

Conclusions and Relevance  In cross-sectional analyses, carriers demonstrated better cognitive and motor performance than did noncarriers with long disease duration, suggesting slower disease progression. A longitudinal follow-up study is required to confirm these findings.

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