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 |
Fingerprint
ASJC Scopus subject areas
- Clinical Neurology
Cite this
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 journal › Article
}
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, 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.
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 -