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.
Original language | English (US) |
---|---|
Pages (from-to) | 319-326 |
Number of pages | 8 |
Journal | Neurology |
Volume | 76 |
Issue number | 4 |
DOIs | |
State | Published - Jan 25 2011 |
Externally published | Yes |
ASJC Scopus subject areas
- Clinical Neurology
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Olfaction in Parkin heterozygotes and compound heterozygotes : The CORE-PD study. / Alcalay, R. N.; Siderowf, A.; Ottman, R.; Caccappolo, E.; Mejia-Santana, H.; Tang, M. X.; Rosado, L.; Louis, E.; Ruiz, D.; Waters, C.; Fahn, S.; Cote, L.; Frucht, S.; Ford, B.; Orbe-Reilly, M.; Ross, B.; Verbitsky, M.; Kisselev, S.; Comella, C.; Colcher, A.; Jennings, D.; Nance, M.; Bressman, S.; Scott, W. K.; Tanner, C.; Mickel, S.; Rezak, M.; Novak, K. E.; Friedman, J. H.; Pfeiffer, R.; Marsh, L.; Hiner, B.; Clark, L. N.; Marder, K.
In: Neurology, Vol. 76, No. 4, 25.01.2011, p. 319-326.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Olfaction in Parkin heterozygotes and compound heterozygotes
T2 - The CORE-PD study
AU - Alcalay, R. N.
AU - Siderowf, A.
AU - Ottman, R.
AU - Caccappolo, E.
AU - Mejia-Santana, H.
AU - Tang, M. X.
AU - Rosado, L.
AU - Louis, E.
AU - Ruiz, D.
AU - Waters, C.
AU - Fahn, S.
AU - Cote, L.
AU - Frucht, S.
AU - Ford, B.
AU - Orbe-Reilly, M.
AU - Ross, B.
AU - Verbitsky, M.
AU - Kisselev, S.
AU - Comella, C.
AU - Colcher, A.
AU - Jennings, D.
AU - Nance, M.
AU - Bressman, S.
AU - Scott, W. K.
AU - Tanner, C.
AU - Mickel, S.
AU - Rezak, M.
AU - Novak, K. E.
AU - Friedman, J. H.
AU - Pfeiffer, R.
AU - Marsh, L.
AU - Hiner, B.
AU - Clark, L. N.
AU - Marder, K.
N1 - Funding Information: Supported by NIH NS36630, UL1 RR024156 (K.S.M.), NS050487, NS060113 (L.N.C.), the Parkinson's Disease Foundation (K.S.M., S.F., and L.N.C.), and P50 NS039764 (W.K.S.). R.N.A. was supported by a Parkinson's Disease Foundation H. Houston Merritt Fellowship in Movement Disorders. Funding Information: Dr. Alcalay has received publishing royalties for Early Onset Parkinson's Disease (Cyberounds, 2010) and receives research support from the Brookdale Foundation. Dr. Siderowf serves on scientific advisory boards for Teva Pharmaceutical Industries Ltd., NeuroSearch, and the Michael J. Fox Foundation; has received speaker honoraria from Teva Pharmaceutical Industries Ltd.; serves as a consultant for Merck Serono, Schering-Plough Corp., Teva Pharmaceutical Industries Ltd., Supernus Pharmaceuticals, Inc.; and has served as a consultant on manganese litigation. Dr. Ottman serves on the scientific advisory board for and holds stock options in Trigeminal Solutions, Inc; has received funding for travel from the International League Against Epilepsy, Fondazione Ettore Majorana E Centro, National Epifellows Forum, the National Institute for Mental Health, and Coriell Institute for Medical Research; serves as a consultant to Ortho-McNeil Janssen Scientific Affairs, LLC.; and has received research support from the NIH. Dr. Caccappolo, Ms. Mejia-Santana, Dr. Tang, and Dr. Rosado report no disclosures. Dr. Louis has served on a scientific advisory board for Pfizer Inc; and has received research support from the NIH (NINDS, NIA) and the Parkinson's Disease Foundation. Ms. Ruiz reports no disclosures. Dr. Waters receives publishing royalties for Diagnosis and Management of Parkinson's Disease (Oxford University Press, 2009); serves as a consultant for Teva Pharmaceutical Industries Ltd.; serves on speakers' bureaus for Teva Pharmaceutical Industries Ltd. and Boehringer Ingelheim; and receives research support from Solvay Pharmaceuticals, Inc., UCB, and Novartis. Dr. Fahn serves on scientific advisory boards for Intech Pharma Pvt. Ltd., IMPAX Laboratories, Inc., Boehringer Ingelheim, Vernalis plc Merz Pharmaceuticals, LLC, Oxford BioMedica Plc, GE Healthcare, RJG Foundation, and Lundbeck, Inc.; has received funding for travel from Boerhinger Ingelheim and Sun Pharmaceutical Industries Ltd.; serves on the editorial board of Current Neurology and Neurosurgery Report; receives publishing royalties for Principles and Practice of Movement Disorders (Elsevier, 2007); has served as a consultant in medico-legal cases; and receives research support from the Parkinson's Disease Foundation and the Smart Family Foundation. Dr. Cote has serves as a consultant for Teva Pharmaceutical Industries Ltd. Dr. Frucht has received funding for travel from Jazz Pharmaceuticals, Lundbeck Inc., and Merz Pharmaceuticals, LLC; receives publishing royalties for Movement Disorders Emergencies (Humana Press, 2005); and has served as a consultant for UCB, Jazz Pharmaceuticals, Merz Pharmaceuticals, LLC, Lundbeck, Inc., GE Healthcare, and Allergan, Inc. Dr. Ford serves on a scientific advisory board for Medtronic, Inc. Dr. Orbe-Reilly, Ms. Ross, Dr. Verbitsky, and Mr. Kisselev report no disclosures. Dr. Comella serves on the editorial board of Sleep Medicine; receives publishing royalties from UpToDate; and serves as a consultant for Allergan, Inc., Ipsen, Eisai Inc., Merz Pharmaceuticals, LLC, and UCB. Dr. Colcher has received speaker honoraria from the Robert Wood Johnson, Plan 365, Healthlogix, and Advanced health Media; and serves on speakers' bureaus for Lundbeck, Inc., Teva Pharmaceutical Industries Ltd., and Ipsen. Dr. Jennings serves on a scientific advisory board for Genzyme Corporation and serves on the speakers' bureaus of Lundbeck Inc. and Teva Pharmaceutical Industries Ltd. Dr. Nance serves on scientific advisory boards for the Spastic Paraplegia Foundation and Parkinson Study Group; receives publishing royalties for Juvenile Huntington's Disease and Other Trinucleotide Repeat Disorders (Oxford University Press, 2009); receives research support from Schwarz Biosciences Inc., NeuroSearch, IMPAX Laboratories, Inc., Medivation, Inc., Neuraltus Pharmaceuticals, Inc., Teva Pharmaceutical Industries Ltd., Juvantia Pharma Ltd., the NIH (NINDS, NHGRI, NCCAM), the National Parkinson Foundation, the Huntington Disease Society of America, the Michael J. Fox Foundation, and Northwestern Dixon Foundation; and her spouse serves on speakers' bureaus for Genentech, Inc. and Schering-Plough Corp. Dr. Bressman serves on scientific advisory boards for the Bachmann-Strauss Dystonia & Parkinson Foundation and the Michael J. Fox Foundation; receives royalties from publication of Clinical Diagnosis and Management of Dystonia (Informa UK Ltd, 2007); and receives research support from the NIH/NINDS, the Michael J. Fox Foundation, and the Bachmann-Strauss Dystonia & Parkinson Foundation. Dr. Scott is co-inventor of a patent re: use of genetic data for risk assessment in age-related macular degeneration, licensed by ArcticDx. Dr. Tanner has served on scientific advisory boards for Allergan, Inc., the Michael J. Fox Foundation, and the Spasmodic Dysphonia Association; has served as a consultant for Stanford University, Pacific Health Research Institute, Sun Health Research Institute, IMPAX Laboratories, Inc., Lundbeck, Inc., and Solstice Neurosciences, Inc.; and has received research support from the Welding Products Manufacturer's Group, the NIH (NINDS, NIEHS), DOD, AHRQ, Parkinson's Institute, Parkinson's Disease Foundation, Michael J. Fox Foundation, Brin Foundation, Stanford University/John Blume Foundation, and Parkinson Alliance (Unity Walk). Dr. Mickel reports no disclosures. Dr. Rezak serves on speakers' bureaus for and has received speaker honoraria from Teva Pharmaceutical Industries Ltd., Allergan Inc., Medtronic, Inc., Novartis, and GlaxoSmithKline; and serves as a consultant for Teva Pharmaceutical Industries Ltd. Dr. Novak receives research support from Cyberonics, Inc., GE Healthcare, the NIH, and the Parkinson's Disease Research Society. Dr. Friedman serves on scientific advisory boards or as a consultant for Teva Pharmaceutical Industries Ltd., EMD Serono, Inc., Biogen Idec, and ACADIA Pharmaceuticals; has received speaker honoraria from Teva Pharmaceutical Industries Ltd., Boehringer Ingelheim, GlaxoSmithKline, United Biosource Corporation, and AstraZeneca; serves as Editor-in-Chief of Medicine & Health/Rhode Island and on the editorial boards of Parkinsonism & Related Disorders and Neurology Reviews; receives publishing royalties for Making the Connection between Brain and Behavior: Coping with Parkinson's Disease (Demos Health, 2007); serves on speakers' bureaus for Teva Pharmaceutical Industries Ltd., Boehringer Ingelheim, GlaxoSmithKline; and receives research support from Teva Pharmaceutical Industries Ltd., Boehringer Ingelheim, GlaxoSmithKline, Pfizer Inc, Cephalon, Inc., ACADIA Pharmaceuticals, EpiVax, Inc., Valeant Pharmaceuticals International, the NIH, and the Michael J. Fox Foundation. Dr. Pfeiffer serves on a scientific advisory board for the National Parkinson Foundation; serves on the editorial board of Parkinsonism and Related Disorders; receives publishing royalties for Parkinson's Disease (Taylor & Francis, 2008), Parkinson's Disease and Nonmotor Dysfunction (Humana, 2008), and Neuro-Gastroenterology (Butterworth-Heinemann, 2008); serves as a consultant for Solvay Pharmaceuticals, Inc., Theravance, Inc., Genactis, Inc., and Schlesinger Associates; serves on speakers' bureaus for and has received speaker honoraria from Boehringer Ingelheim, Novartis, and Teva Pharmaceutical Industries Ltd.; receives research support from Novartis, Boehringer Ingelheim, UCB/ SCHWARZ PHARMA, Santhera Pharmaceuticals, and Molecular Biometrics, Inc., Columbia University, Weill Cornell Medical College, Northwestern University, Indiana University, Parkinson Study Group, and the Michael J. Fox Foundation; and has served as a consultant in medico-legal cases. Dr. Marsh serves on scientific advisory boards for the National Parkinson Foundation, American Parkinson's Disease Association, and the Parkinson Study Group; receives publishing royalties for Psychiatric Issues in Parkinson's Disease: A Practical Guide (Taylor & Francis, Informa, 2005); serves as a consultant for Merck Serono, Boehringe Ingelheim, ACADIA Pharmaceuticals, and Lundbeck, Inc. (Ovation Pharmaceuticals); and receives research support from Forest Laboratories, Inc., Eli Lilly and Company, Boehringer Ingelheim, the NIH, Baylor College of Medicine, and the Michael J. Fox Foundation. Dr. Hiner has received speaker honoraria from Teva Pharmaceutical Industries Ltd. Dr. Clark reports no disclosures. Dr. Marder serves on the editorial board of Neurology; and receives research support from Amarin Corporation, Boehringer Ingelheim, NeuroSearch, the NIH, the Parkinson Disease Foundation, the Huntington's Disease Society of America, Parkinson Study Group, and the Michael J. Fox Foundation.
PY - 2011/1/25
Y1 - 2011/1/25
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79251592293&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79251592293&partnerID=8YFLogxK
U2 - 10.1212/WNL.0b013e31820882aa
DO - 10.1212/WNL.0b013e31820882aa
M3 - Article
C2 - 21205674
AN - SCOPUS:79251592293
VL - 76
SP - 319
EP - 326
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 4
ER -