Cognitive and motor function in long-duration PARKIN-associated Parkinson disease

Roy N Alcalay¹, Elise Caccappolo², Helen Mejia-Santana², Ming Xin Tang¹, Llency Rosado², Martha Orbe Reilly², Diana Ruiz², Elan D Louis³, Cynthia L Comella⁴, Martha A Nance⁵, Susan B Bressman⁶, William K Scott⁷, Caroline M Tanner⁸, Susan F Mickel⁹, Cheryl H Waters², Stanley Fahn², Lucien J Cote¹⁰, Steven J Frucht², Blair Ford², Michael Rezak¹¹, Kevin E Novak¹², Joseph H Friedman¹³, Ronald F Pfeiffer¹⁴, Laura Marsh¹⁵, Bradley Hiner¹⁶, Haydeh Payami¹⁷, Eric Molho¹⁸, Stewart A Factor¹⁹, John G Nutt²⁰, Carmen Serrano²¹, Maritza Arroyo²¹, Ruth Ottman²², Michael W Pauciulo²³, William C Nichols²³, Lorraine N Clark²⁴, Karen S Marder³

Affiliations

¹ Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York2Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York.
² Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York.
³ Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York2Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York3Gertru.
⁴ Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois.
⁵ Struthers Parkinson's Center, Park Nicollet Clinic, Golden Valley, Minnesota.
⁶ The Alan and Barbara Mirken Department of Neurology, Beth Israel Medical Center, New York, New York8Department of Neurology, Albert Einstein College of Medicine, Bronx, New York.
⁷ Dr John T. Macdonald Foundation, Department of Human Genetics, Miami Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, Florida.
⁸ Parkinson's Institute, Sunnyvale, and Department of Health Research and Policy, Stanford University, Palo Alto, California.
⁹ Marshfield Clinic, Department of Neurology, Marshfield, Wisconsin.
¹⁰ Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York3Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, New York.
¹¹ Central DuPage Hospital, Neurosciences Institute, Movement Disorders Center, Winfield, Illinois.
¹² Department of Neurology, NorthShore University Health System, Evanston, Illinois14Department of Neurology, University of Chicago, Pritzker School of Medicine, Chicago, Illinois.
¹³ Department of Neurology, Butler Hospital, Providence, Rhode Island16Department of Neurology, Alpert Medical School, Brown University, Providence, Rhode Island.
¹⁴ Department of Neurology, College of Medicine, University of Tennessee Health Science Center, Memphis.
¹⁵ Morris 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.
¹⁶ Department of Neurology, Medical College of Wisconsin, Milwaukee.
¹⁷ New York State Department of Health Wadsworth Center, Albany, New York.
¹⁸ Parkinson's Disease and Movement Disorders Center of Albany Medical Center, Albany, New York.
¹⁹ Department of Neurology, Emory University, Atlanta, Georgia.
²⁰ Portland VA Medical Center, Parkinson Disease Research, Education and Clinical Center, and Oregon Health and Science University, Portland.
²¹ Department of Neurology, University of Puerto Rico, San Juan.
²² Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York3Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, New York4Department of Epidemiology, Mailman School of P.
²³ Division of Human Genetics, Cincinnati Children's Hospital Medical Center, and Department of Pediatrics; University of Cincinnati College of Medicine, Ohio.
²⁴ Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York27Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New Yor.

PMID: 24190026
PMCID: PMC3947132
DOI: 10.1001/jamaneurol.2013.4498

Multicenter Study

Cognitive and motor function in long-duration PARKIN-associated Parkinson disease

Roy N Alcalay et al. JAMA Neurol. 2014 Jan.

. 2014 Jan;71(1):62-7.

doi: 10.1001/jamaneurol.2013.4498.

Authors

Affiliations

¹ Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York2Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York.
² Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York.
³ Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York2Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York3Gertru.
⁴ Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois.
⁵ Struthers Parkinson's Center, Park Nicollet Clinic, Golden Valley, Minnesota.
⁶ The Alan and Barbara Mirken Department of Neurology, Beth Israel Medical Center, New York, New York8Department of Neurology, Albert Einstein College of Medicine, Bronx, New York.
⁷ Dr John T. Macdonald Foundation, Department of Human Genetics, Miami Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, Florida.
⁸ Parkinson's Institute, Sunnyvale, and Department of Health Research and Policy, Stanford University, Palo Alto, California.
⁹ Marshfield Clinic, Department of Neurology, Marshfield, Wisconsin.
¹⁰ Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York3Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, New York.
¹¹ Central DuPage Hospital, Neurosciences Institute, Movement Disorders Center, Winfield, Illinois.
¹² Department of Neurology, NorthShore University Health System, Evanston, Illinois14Department of Neurology, University of Chicago, Pritzker School of Medicine, Chicago, Illinois.
¹³ Department of Neurology, Butler Hospital, Providence, Rhode Island16Department of Neurology, Alpert Medical School, Brown University, Providence, Rhode Island.
¹⁴ Department of Neurology, College of Medicine, University of Tennessee Health Science Center, Memphis.
¹⁵ Morris 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.
¹⁶ Department of Neurology, Medical College of Wisconsin, Milwaukee.
¹⁷ New York State Department of Health Wadsworth Center, Albany, New York.
¹⁸ Parkinson's Disease and Movement Disorders Center of Albany Medical Center, Albany, New York.
¹⁹ Department of Neurology, Emory University, Atlanta, Georgia.
²⁰ Portland VA Medical Center, Parkinson Disease Research, Education and Clinical Center, and Oregon Health and Science University, Portland.
²¹ Department of Neurology, University of Puerto Rico, San Juan.
²² Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York3Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, New York4Department of Epidemiology, Mailman School of P.
²³ Division of Human Genetics, Cincinnati Children's Hospital Medical Center, and Department of Pediatrics; University of Cincinnati College of Medicine, Ohio.
²⁴ Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York27Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New Yor.

PMID: 24190026
PMCID: PMC3947132
DOI: 10.1001/jamaneurol.2013.4498

Abstract

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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Conflict of interest statement

Disclosure: The authors report no conflicts of interest.

References

1. Lucking CB, Durr A, Bonifati V, et al. Association between early-onset Parkinson’s disease and mutations in the parkin gene. N Engl J Med. 2000;342:1560–1567. - PubMed
1. Caccappolo E, Alcalay RN, Mejia-Santana H, et al. Neuropsychological Profile of Parkin Mutation Carriers with and without Parkinson Disease: The CORE-PD Study. J Int Neuropsychol Soc. 2011;17:91–100. - PMC - PubMed
1. Lohmann E, Thobois S, Lesage S, et al. A multidisciplinary study of patients with early-onset PD with and without parkin mutations. Neurology. 2009;72:110–116. - PMC - PubMed
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1. Alcalay RN, Caccappolo E, Mejia-Santana H, et al. Frequency of known mutations in early-onset Parkinson disease: implication for genetic counseling: the consortium on risk for early onset Parkinson disease study. Arch Neurol. 2010;67:1116–1122. - PMC - PubMed

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Cognitive and motor function in long-duration PARKIN-associated Parkinson disease

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Cognitive and motor function in long-duration PARKIN-associated Parkinson disease

Authors

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Abstract

Conflict of interest statement

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