Year: 2010
Type: article
Study design: Observational Study
Abstract: BACKGROUND: While Parkinson disease (PD) is consistently associated with impaired olfaction, one study reported better olfaction among Parkin mutation carriers than noncarriers. Whether olfaction differs between Parkin mutation heterozygotes and carriers of 2 Parkin mutations (compound heterozygotes) is unknown. OBJECTIVE: To assess the relationship between Parkin genotype and olfaction in PD probands and their unaffected relatives. METHODS: We administered the University of Pennsylvania Smell Identification Test (UPSIT) to 44 probands in the Consortium on Risk for Early-Onset Parkinson Disease study with PD onset ≤50 years (10 Parkin mutation heterozygotes, 9 compound heterozygotes, 25 noncarriers) and 80 of their family members (18 heterozygotes, 2 compound heterozygotes, 60 noncarriers). In the probands, linear regression was used to assess the association between UPSIT score (outcome) and Parkin genotype (predictor), adjusting for covariates. Among family members without PD, we compared UPSIT performance in heterozygotes vs noncarriers using generalized estimating equations, adjusting for family membership, age, gender, and smoking. RESULTS: Among probands with PD, compound heterozygotes had higher UPSIT scores (31.9) than heterozygotes (20.1) or noncarriers (19.9) (p < 0.001). These differences persisted after adjustment for age, gender, disease duration, and smoking. Among relatives without PD, UPSIT performance was similar in heterozygotes (32.5) vs noncarriers (32.4), and better than in heterozygotes with PD (p = 0.001). CONCLUSION: Olfaction is significantly reduced among Parkin mutation heterozygotes with PD but not among their heterozygous relatives without PD. Compound heterozygotes with PD have olfaction within the normal range. Further research is required to assess whether these findings reflect different neuropathology in Parkin mutation heterozygotes and compound heterozygotes.
Source: Neurology
Authors: R.N. Alcalay, A. Siderowf, R. Ottman, E. Caccappolo, H. Mejia-Santana, M.-X. Tang, L. Rosado, E. Louis, D. Ruiz, C. Waters, S. Fahn, L. Cote, S. Frucht, B. Ford, M. Orbe-Reilly, B. Ross, M. Verbitsky, S. Kisselev, C. Comella, A. Colcher, D. Jennings, M. Nance, S. Bressman, W.K. Scott, C. Tanner, S. Mickel, M. Rezak, K.E. Novak, J.H. Friedman, R. Pfeiffer, L. Marsh, B. Hiner, L.N. Clark, K. Marder
Institutions: Columbia University, University of Pennsylvania, Institute for Neurodegenerative Disorders, Park Nicollet Health Services, Yeshiva University, University of Miami, Marshfield Clinic, Marshfield Clinic, Marshfield Clinic, Endeavor Health, University of Chicago, University of Tennessee Health Science Center, Brown University, Johns Hopkins University, Medical College of Wisconsin, Rush University
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: U.S. Department of Defense, Michael J. Fox Foundation for Parkinson's Research, National Parkinson Foundation, Parkinson's Disease Foundation, Park Nicollet Foundation, Eli Lilly and Company, Pfizer, AstraZeneca, GlaxoSmithKline, Biogen, Teva Pharmaceutical Industries, Brown University, University of Miami, University of Pennsylvania, Northwestern University, University of Chicago, Rush University, Brin Wojcicki Foundation, Dr. John T. MacDonald Foundation, Valeant Pharmaceuticals International, NorthShore University HealthSystem, Parkinson Alliance, Parkinson Study Group, Amarin Corporation, ACADIA Pharmaceuticals, Spastic Paraplegia Foundation, University of Warwick, University of Oxford, Eisai, Merz Pharmaceuticals, H. Lundbeck A/S, Ipsen, National Institutes of Health, Agency for Healthcare Research and Quality, Genentech, EMD Serono, Forest Laboratories, Health Science Center, University of Tennessee, Weill Cornell Medical College, Allergan, Pritzker School of Medicine, Parkinsonfonden, Leonard M. Miller School of Medicine, Leonard M. Miller School of Medicine, University of Miami, National Human Genome Research Institute, National Center for Complementary and Alternative Medicine, National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences, National Center for Research Resources, Mailman School of Public Health, Columbia University
OpenAlex ID: W2095002145