Skip to main content Accessibility help
×
Home
Hostname: page-component-5c569c448b-q9r9l Total loading time: 0.326 Render date: 2022-07-06T08:32:42.067Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "useRatesEcommerce": false, "useNewApi": true } hasContentIssue true

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

Published online by Cambridge University Press:  24 November 2010

Elise Caccappolo
Affiliation:
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York
Roy N. Alcalay
Affiliation:
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York
Helen Mejia-Santana
Affiliation:
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York
Ming-X. Tang
Affiliation:
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York
Brian Rakitin
Affiliation:
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York
Llency Rosado
Affiliation:
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York
Elan D. Louis
Affiliation:
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, New York Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York
Cynthia L. Comella
Affiliation:
Department of Neurology/Movement Disorder Section, Chicago, Illinois
Amy Colcher
Affiliation:
Parkinson's Disease and Movement Disorders Center, Pennsylvania Hospital, Philadelphia, Pennsylvania
Danna Jennings
Affiliation:
The Institute for Neurodegenerative Disorders, New Haven, Connecticut
Martha A. Nance
Affiliation:
Struthers Parkinson's Center, Park Nicollet Clinic, Golden Valley, Minnesota
Susan Bressman
Affiliation:
The Alan and Barbara Mirken Department of Neurology, Beth Israel Medical Center, New York, New York Department of Neurology, Albert Einstein College of Medicine, Bronx, New York
William K. Scott
Affiliation:
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
Caroline M. Tanner
Affiliation:
Parkinson's Institute, Sunnyvale, California
Susan F. Mickel
Affiliation:
Marshfield Clinic, Department of Neurology, Marshfield, Wisconsin
Howard F. Andrews
Affiliation:
New York State Psychiatric Institute, Data Coordinating Center, New York, New York
Cheryl Waters
Affiliation:
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York
Stanley Fahn
Affiliation:
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York
Lucien J. Cote
Affiliation:
Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, New York
Steven Frucht
Affiliation:
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York
Blair Ford
Affiliation:
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York
Michael Rezak
Affiliation:
Department of Neurology, at North Shore University Health System, Evanston, Illinois Department of Neurology, at Northwestern University, Feinberg School of Medicine, Chicago, Illinois
Kevin Novak
Affiliation:
Department of Neurology, at North Shore University Health System, Evanston, Illinois Department of Neurology, at Northwestern University, Feinberg School of Medicine, Chicago, Illinois
Joseph H. Friedman
Affiliation:
Parkinson's Disease and Movement Disorders Center of NeuroHealth, Warwick, Rhode Island Department of Clinical Neurosciences, The Warren Alpert School of Medicine of Brown University, Providence, Rhode Island
Ronald F. Pfeiffer
Affiliation:
Department of Neurology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee
Laura Marsh
Affiliation:
Morris K. Udall Parkinson's Disease Research Center of Excellence, Johns Hopkins University School of Medicine, Baltimore, Maryland Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine, Baltimore, Maryland Department of Neurology and Neurological Sciences Johns Hopkins University School of Medicine, Baltimore, Maryland
Brad Hiner
Affiliation:
Medical College of Wisconsin, Milwaukee, Wisconsin
Andrew D. Siderowf
Affiliation:
Department of Neurology, University of Pennsylvania Health System, Philadelphia, Pennsylvania
Barbara M. Ross
Affiliation:
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York
Miguel Verbitsky
Affiliation:
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York
Sergey Kisselev
Affiliation:
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York
Ruth Ottman
Affiliation:
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, New York Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York Division of Epidemiology, New York State Psychiatric Institute, New York, NY
Lorraine N. Clark
Affiliation:
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York
Karen S. Marder*
Affiliation:
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, New York Department of Psychiatry, Columbia University Medical Center, New York, New York
*
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

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)

Type
Research Articles
Copyright
Copyright © The International Neuropsychological Society 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Alcalay, R.N., Mejia-Santana, H., Tang, M.X., Rakitin, B., Rosado, L., Ross, B., Caccappolo, E. (2010). Self-report of cognitive impairment and mini-mental state examination performance in PRKN, LRRK2, and GBA carriers with early onset Parkinson’s disease. Journal of Clinical and Experimental Neuropsychiatry, 32(7), 775779. doi:10.1080/13803390903521018CrossRefGoogle ScholarPubMed
Artioli i Fortuny, L., Romo, D.H., Heaton, R.K., Pardee, R.E. (1999). Manuel de Normas Procedimientos para la Bateria Neuropsicologica en Espanol. Tucson, AZ: M Press.Google Scholar
Beck, A.T., Ward, C., Mendelson, M., Mock, J., Erbaugh, J. (1961). An inventory for measuring depression. Archives of General Psychiatry, 4, 561571. Retrieved from http://archpsyc.ama-assn.org/CrossRefGoogle ScholarPubMed
Benton, A.L. (1974). Revised visual retention test (4th ed.). New York: The Psychological Corporation.Google Scholar
Benton, A.L., Sivan, A.B., Hamsher, K., Varney, N.R., Spreen, O. (1994). Contributions to neuropsychological assessment. New York: Oxford University Press.Google Scholar
Clark, L.N., Afridi, S., Karlins, E., Wang, Y., Mejia-Santana, H., Harris, J., Marder, K. (2006). Case-control study of the parkin gene in early-onset Parkinson disease. Archives of Neurology, 63(4), 548552. Retrieved from http://archneur.ama-assn.org/CrossRefGoogle Scholar
Clark, L.N., Haamer, E., Mejia-Santana, H., Harris, J., Lesage, S., Durr, A., Marder, K. (2007). Construction and validation of a Parkinson’s disease mutation genotyping array for the Parkin gene. Movement Disorders, 22(7), 932937. doi:10.1002/mds.21419CrossRefGoogle ScholarPubMed
Dujardin, D.K., Duhamel, A., Becquet, E., Grunberg, C., Defebvre, L., Destee, L. (1999). Neuropsychological abnormalities in first degree relatives of patients with Parkinson’s disease. Journal of Neurology, Neurosurgery, and Psychiatry, 67(3), 323328. Retrieved from http://jnnp.bmj.com/CrossRefGoogle Scholar
Fahn, S.R., Elton, R.L., & Members of the UPDRS Development Committee (1987). The Unified Parkinson’s Disease Rating Scale. In S. Fahn, C.D. Marsden, D.B. Calne & M. Goldstein (Eds.), Recent developments in Parkinson’s disease (Vol. 2, pp. 153163, 293–304). Florham Park, NJ: Macmillan Healthcare Information.Google Scholar
Folstein, M.F., Folstein, S.E., McHugh, P.R. (1975). Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12(3), 189198. Retrieved from http://www.elsevier.com/wps/find/journaldescription.cws_home/241/descriptiondescriptionCrossRefGoogle Scholar
Foroud, T., Uniacke, S.K., Liu, L., Pankratz, N., Rudolph, A., Halter, C., Nichols, W.C. (2003). Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease. Neurology, 60(5), 796801. Retrieved from http://www.neurology.org/CrossRefGoogle Scholar
Golden, C. (1978). The Stroop Color and Word Test: A manual for clinical and experimental uses. Chicago, IL: Stoelting.Google Scholar
Hedrich, K., Kann, M., Lanthaler, A.J., Dalski, A., Eskelson, C., Landt, O., Klein, C. (2001). The importance of gene dosage studies: Mutational analysis of the parkin gene in early-onset parkinsonism. Human Molecular Genetics, 10(16), 16491656. Retrieved from http://hmg.oxfordjournals.org/current.dtlCrossRefGoogle Scholar
Hughes, A.J., Daniel, S.E., Kilford, L., Lees, A.J. (1992). Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: A clinico-pathological study of 100 cases. Journal of Neurology, Neurosurgery, and Psychiatry, 55(3), 181184. Retrieved from http://jnnp.bmj.com/CrossRefGoogle ScholarPubMed
Khan, N.L., Graham, E., Critchley, P., Schrag, A.E., Wood, N.W., Lees, A.J., Quinn, N. (2003). Parkin disease: A phenotypic study of a large case series. Brain, 126(Pt. 6), 12791292. doi:10.1093/brain/awg142CrossRefGoogle Scholar
Khan, N.L., Horta, W., Eunson, L., Graham, E., Johnson, J.O., Chang, S., Lees, A.J. (2005). Parkin disease in a Brazilian kindred: Manifesting heterozygotes and clinical follow-up over 10 years. Movement Disorders, 20(4), 479484. doi:10.1002/mds.20335CrossRefGoogle Scholar
Kitada, T., Asakawa, S., Hattori, N., Matsumine, H., Yamamura, Y., Minoshima, S., Shimizu, N. (1998). Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature, 392(6676), 605608. Retrieved from http://www.nature.com/nature/journal/v392/n6676/Google Scholar
Lesage, S., Lohmann, E., Tison, F., Durit, F., Durr, A., Brice, A. (2008). Rare heterozygous parkin variants in French early-onset Parkinson disease patients and controls. Journal of Medical Genetics, 45(1), 4346. doi:10.1136/jmg.2007.051854CrossRefGoogle Scholar
Levin, B.E., Llabre, M.M., Weiner, W.J. (1989). Cognitive impairments associated with early Parkinson’s disease. Neurology, 39, 557561. Retrieved from http://www.neurology.org/CrossRefGoogle ScholarPubMed
Lewis, F.M., Lapointe, L.L., Murdoch, B.E. (1998). Language impairment in Parkinson’s disease. Aphasiology, 12, 193206.CrossRefGoogle Scholar
Lincoln, S.J., Wiley, J., Lynch, T., Langston, J.W., Chen, R., Lang, A., Farrer, M. (2003). Parkin-proven disease: Common founders but divergent phenotypes. Neurology, 60(10), 16051610. Retrieved from http://www.neurology.org/CrossRefGoogle ScholarPubMed
Lohmann, E., Thobois, S., Lesage, S., Broussolle, E., du Montcel, S.T., Ribeiro, M.J., Brice, A. (2009). A multidisciplinary study of patients with early-onset PD with and without parkin mutations. Neurology, 72(2), 110116. doi:01.wnl.0000327098.86861.d4CrossRefGoogle ScholarPubMed
Lucking, C.B., Durr, A., Bonifati, V., Vaughan, J., De Michele, G., Gasser, T., Brice, A. (2000). Association between early-onset Parkinson’s disease and mutations in the parkin gene. New England Journal of Medicine, 342(21), 15601567. Retrieved from http://www.nejm.org/CrossRefGoogle ScholarPubMed
Luteijn, F.B., Barelds, D.P.H. (2004). Groningen Intelligence Test 2 (GIT2 Manual). Amsterdam, The Netherlands: Harcourt.Google Scholar
Marder, K., Levy, G., Louis, E.D., Mejia-Santana, H., Cote, L., Andrews, H., Ottman, R. (2003a). Familial aggregation of early- and late-onset Parkinson’s disease. Annals of Neurology, 54(4), 507513. doi:10.1002/ana.10711CrossRefGoogle Scholar
Marder, K., Levy, G., Louis, E.D., Mejia-Santana, H., Cote, L., Andrews, H., Ottman, R. (2003b). Accuracy of family history data on Parkinson’s disease. Neurology, 6(1), 1823. Retrieved from http://www.neurology.org/CrossRefGoogle Scholar
Marder, K.T., Tang, M.X., Mejia-Santana, H., Rosado, L., Louis, E.D., Comella, C., Clark, L.N. (2009). Predictors of Parkin Mutations in Early Onset Parkinson disease: The CORE-PD Study. Archives of Neurology, 67(6), 731738. Retrieved from http://archneur.ama-assn.org/Google Scholar
Moro, E., Volkmann, J., Konig, I.R., Winkler, S., Hiller, A., Hassin-Baer, S., Klein, C. (2008). Bilateral subthalamic stimulation in Parkin and PINK1 parkinsonism. Neurology, 70(14), 11861191. Retrieved from http://www.neurology.org/CrossRefGoogle ScholarPubMed
Muslimovic, D., Post, B., Speelman, J.D., DeHaan, R.J., Schmand, B. (2005). Cognitive profile of patients with newly diagnosed Parkinson disease. Neurology, 65(8), 12391245. Retrieved from http://www.neurology.org/CrossRefGoogle ScholarPubMed
Muslimovic, D., Post, B., Speelman, J.D., DeHaan, R.J., Schmand, B. (2009). Cognitive decline in Parkinson’s disease: A prospective longitudinal study. Journal of the International Neuropsychological Society, 15(3), 426437. doi:10.1017/S1355617709090614CrossRefGoogle ScholarPubMed
Oliveira, S.A., Scott, W.K., Martin, E.R., Nance, M.A., Watts, R.L., Hobble, J.P., Vance, J.M. (2003). Parkin mutations and susceptibility alleles in late-onset Parkinson’s disease. Annals of Neurology, 53(5), 624629. doi:10.1002/ana.10524CrossRefGoogle Scholar
Perez, F.A., Palmiter, R.D. (2005). Parkin-deficient mice are not a robust model of parkinsonism. Proceedings of the National Academy of Science of the United States of America, 102(6), 21742179. Retrieved from http://www.pnas.org/CrossRefGoogle Scholar
Periquet, M., Latouche, M., Lohmann, E., Rawal, N., DeMichele, G., Ricard, S., Brice, A. (2003). Parkin mutations are frequent in patients with isolated early-onset parkinsonism. Brain, 126(Pt. 6), 12711278. doi:10.1093/brain/awg136CrossRefGoogle ScholarPubMed
Pramstaller, P.P., Schlossmacher, M.G., Jacques, T.S., Scaravilli, F., Eskelson, C., Pepivani, I., Klein, C. (2005). Lewy body Parkinson’s disease in a large pedigree with 77 Parkin mutation carriers. Annals of Neurology, 58(3), 411422. doi:10.1002/ana.20587CrossRefGoogle Scholar
Reitan, R.M., Wolfson, D. (1992). Conventional intelligence measurements and neuropsychological concepts of adaptive abilities. Journal of Clinical Psychology, 48(4), 521529. doi:10.1002/1097-4679(199207)3.0.CO;2-C>CrossRefGoogle ScholarPubMed
Schrag, A., Schott, J.M. (2006). Epidemiological, clinical, and genetic characteristics of early-onset parkinsonism. Lancet Neurology, 5(4), 355363. doi:10.1016/S1474-4422(06)70411-2CrossRefGoogle ScholarPubMed
Spreen, O., Strauss, E. (1991). A compendium of neuropsychological tests: Administration, norms, and commentary. New York: Oxford University Press.Google Scholar
van Nuenen, B.F., Weiss, M.M., Bloem, B.R., Reetz, K., van Eimeren, T., Lohmann, K., Siebner, H.R. (2009). Heterozygous carriers of a Parkin or PINK1 mutation share a common functional endophenotype. Neurology, 72(12), 10411047. Retrieved from http://www.neurology.org/CrossRefGoogle Scholar
Wang, Y., Clark, L.N., Louis, E.D., Mejia-Santana, H., Harris, J., Cote, L.C., Marder, K. (2008). Risk of Parkinson disease in carriers of parkin mutations: Estimation using the kin-cohort method. Archives of Neurology, 65(4), 467474. Retrieved from http://archneur.ama-assn.org/CrossRefGoogle Scholar
Wechsler, D. (1987). The Wechsler memory scale-revised. New York: The Psychological Corporation.Google Scholar
Woods, S.P., Delis, D.C., Scott, J.C., Kramer, J.H., Holdnack, J.A. (2006). The California Verbal Learning Test--second edition: Test-retest reliability, practice effects, and reliable change indices for the standard and alternate forms. Archives of Clinical Neuropsychology, 21(5), 413420. doi:10.1016/j.acn.2006.06.002CrossRefGoogle ScholarPubMed
Zeger, S.L., Liang, K.Y. (1986). Longitudinal data analysis for discrete and continuous outcomes. Biometrics, 42(1), 121130.CrossRefGoogle Scholar
Zhu, X.R., Maskri, L., Herold, C., Bader, V., Stichel, C.G., Gunturkun, O., Lubbert, H. (2007). Non-motor behavioural impairments in parkin-deficient mice. European Journal of Neuroscience, 26(7), 19021911.CrossRefGoogle ScholarPubMed
Supplementary material: File

Caccappolo supplementary material

Table 3.doc

Download Caccappolo supplementary material(File)
File 351 KB
17
Cited by

Save article to Kindle

To save this article to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

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

Save article to Dropbox

To save this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about saving content to Dropbox.

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

Save article to Google Drive

To save this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about saving content to Google Drive.

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

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *