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

  • Elise Caccappolo (a1) (a2), Roy N. Alcalay (a1), Helen Mejia-Santana (a1), Ming-X. Tang (a1) (a2), Brian Rakitin (a1) (a2), Llency Rosado (a1), Elan D. Louis (a1) (a2) (a3) (a4), Cynthia L. Comella (a5), Amy Colcher (a6), Danna Jennings (a7), Martha A. Nance (a8), Susan Bressman (a9) (a10), William K. Scott (a11), Caroline M. Tanner (a12), Susan F. Mickel (a13), Howard F. Andrews (a14), Cheryl Waters (a1), Stanley Fahn (a1), Lucien J. Cote (a3), Steven Frucht (a1), Blair Ford (a1), Michael Rezak (a15) (a16), Kevin Novak (a15) (a16), Joseph H. Friedman (a17) (a18), Ronald F. Pfeiffer (a19), Laura Marsh (a20) (a21) (a22), Brad Hiner (a23), Andrew D. Siderowf (a24), Barbara M. Ross (a2), Miguel Verbitsky (a2), Sergey Kisselev (a2), Ruth Ottman (a1) (a3) (a4) (a25), Lorraine N. Clark (a2) (a26) and Karen S. Marder (a1) (a2) (a3) (a27)...


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)


Corresponding author

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


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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:10.1080/13803390903521018
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.
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
Benton, A.L. (1974). Revised visual retention test (4th ed.). New York: The Psychological Corporation.
Benton, A.L., Sivan, A.B., Hamsher, K., Varney, N.R., Spreen, O. (1994). Contributions to neuropsychological assessment. New York: Oxford University Press.
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
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.21419
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
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.
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
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
Golden, C. (1978). The Stroop Color and Word Test: A manual for clinical and experimental uses. Chicago, IL: Stoelting.
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
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
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/awg142
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.20335
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
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.2007.051854
Levin, B.E., Llabre, M.M., Weiner, W.J. (1989). Cognitive impairments associated with early Parkinson’s disease. Neurology, 39, 557561. Retrieved from
Lewis, F.M., Lapointe, L.L., Murdoch, B.E. (1998). Language impairment in Parkinson’s disease. Aphasiology, 12, 193206.
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
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.d4
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
Luteijn, F.B., Barelds, D.P.H. (2004). Groningen Intelligence Test 2 (GIT2 Manual). Amsterdam, The Netherlands: Harcourt.
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.10711
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
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
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
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
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/S1355617709090614
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.10524
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
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/awg136
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.20587
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)
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)70411-2
Spreen, O., Strauss, E. (1991). A compendium of neuropsychological tests: Administration, norms, and commentary. New York: Oxford University Press.
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
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
Wechsler, D. (1987). The Wechsler memory scale-revised. New York: The Psychological Corporation.
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.2006.06.002
Zeger, S.L., Liang, K.Y. (1986). Longitudinal data analysis for discrete and continuous outcomes. Biometrics, 42(1), 121130.
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.
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