Olfaction in Parkin heterozygotes and compound heterozygotes: The CORE-PD study

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. ColcherD. Jennings, M. Nance, S. Bressman, W. K. Scott, C. Tanner, S. Mickel, M. Rezak, K. E. Novak, J. H. Friedman, Ronald Pfeiffer, L. Marsh, B. Hiner, L. N. Clark, K. Marder

Research output: Contribution to journalArticle

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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 languageEnglish (US)
Pages (from-to)319-326
Number of pages8
JournalNeurology
Volume76
Issue number4
DOIs
StatePublished - Jan 25 2011
Externally publishedYes

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Smell
Heterozygote
Parkinson Disease
Mutation
Smoking
Genotype

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Alcalay, R. N., Siderowf, A., Ottman, R., Caccappolo, E., Mejia-Santana, H., Tang, M. X., ... Marder, K. (2011). Olfaction in Parkin heterozygotes and compound heterozygotes: The CORE-PD study. Neurology, 76(4), 319-326. https://doi.org/10.1212/WNL.0b013e31820882aa

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, Ronald; 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 journalArticle

Alcalay, RN, Siderowf, A, Ottman, R, Caccappolo, E, Mejia-Santana, H, Tang, MX, 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, WK, Tanner, C, Mickel, S, Rezak, M, Novak, KE, Friedman, JH, Pfeiffer, R, Marsh, L, Hiner, B, Clark, LN & Marder, K 2011, 'Olfaction in Parkin heterozygotes and compound heterozygotes: The CORE-PD study', Neurology, vol. 76, no. 4, pp. 319-326. https://doi.org/10.1212/WNL.0b013e31820882aa
Alcalay RN, Siderowf A, Ottman R, Caccappolo E, Mejia-Santana H, Tang MX et al. Olfaction in Parkin heterozygotes and compound heterozygotes: The CORE-PD study. Neurology. 2011 Jan 25;76(4):319-326. https://doi.org/10.1212/WNL.0b013e31820882aa
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, Ronald ; Marsh, L. ; Hiner, B. ; Clark, L. N. ; Marder, K. / Olfaction in Parkin heterozygotes and compound heterozygotes : The CORE-PD study. In: Neurology. 2011 ; Vol. 76, No. 4. pp. 319-326.
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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.",
author = "Alcalay, {R. N.} and A. Siderowf and R. Ottman and E. Caccappolo and H. Mejia-Santana and Tang, {M. X.} and L. Rosado and E. Louis and D. Ruiz and C. Waters and S. Fahn and L. Cote and S. Frucht and B. Ford and M. Orbe-Reilly and B. Ross and M. Verbitsky and S. Kisselev and C. Comella and A. Colcher and D. Jennings and M. Nance and S. Bressman and Scott, {W. K.} and C. Tanner and S. Mickel and M. Rezak and Novak, {K. E.} and Friedman, {J. H.} and Ronald Pfeiffer and L. Marsh and B. Hiner and Clark, {L. N.} and K. Marder",
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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, Ronald

AU - Marsh, L.

AU - Hiner, B.

AU - Clark, L. N.

AU - Marder, K.

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.

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