TY - JOUR
T1 - Olfactory dysfunction in LRRK2 G2019S mutation carriers
AU - Saunders-Pullman, R.
AU - Stanley, K.
AU - Wang, C.
AU - Luciano, M. San
AU - Shanker, V.
AU - Hunt, A.
AU - Severt, L.
AU - Raymond, D.
AU - Ozelius, L. J.
AU - Lipton, R. B.
AU - Bressman, S. B.
N1 - Funding Information:
Study funding: Supported by the Michael J Fox Foundation (R.S.-P., S.B.B.), the NIH/NINDS (K23NS047256, R.S.-P.) , the Thomas Hartman Foundation for Parkinson's Research, and NIH/NIA (AG03949, R.B.L.) .
Funding Information:
Dr. Saunders-Pullman serves on the Scientific Advisory Board of the Dystonia Medical Research Foundation. She has received research support from the NIH/NINDS, the Michael J Fox Foundation for Parkinson's Research, the Thomas Hartman Foundation for Parkinson's Research, the Bachmann-Strauss Dystonia Parkinson's Foundation, and the Marcled Foundation. She has received an honorarium from GE Healthcare. K. Stanley reports no disclosures. Dr. Wang receives research support from Bristol-Myers Squibb. Dr. San Luciano has received research support from the American Academy of Neurology Foundation. Dr. Shanker serves as a consultant for Teva Pharmaceutical Industries Ltd. and ECRI. Dr. Hunt reports no disclosures. Dr. Severt has received speaker honoraria from Teva Pharmaceutical Industries Ltd., Novartis, Ipsen, and Allergan, Inc.; and receives research support from Teva Pharmaceutical Industries Ltd., Ceregene, and Chelsea Therapeutics. D. Raymond reports no disclosures. Dr. Ozelius serves on scientific advisory boards for the Dystonia Medical Research Foundation, the Bachmann-Strauss Dystonia & Parkinson Foundation, the Benign Essential Blepharospasm Research Foundation, and the National Spasmodic Dysphonia Association; is listed as an author on patents re: Torsin, Torsin genes and methods of use, and Nucleic acids, methods and kits for the diagnosis of DYT6 primary torsion dystonia; receives research support from the NIH, the Dystonia Medical Research Foundation, and the Bachmann Strauss Dystonia Parkinson Foundation; and receives royalties from Athena Diagnostics, Inc. for a patent re: Torsin, Torsin genes and methods of use. Dr. Lipton serves on scientific advisory boards for Allergan, Inc., Merck Serono, Neuralieve, Inc., and Pfizer Inc.; has received funding for travel from the American Headache Society, Cognimed, Diamond Headache Clinic Research, Market Force Communications, Merck Serono, Migraine Research Foundation, Scienta, and Talley Management; serves as Associate Editor of Cephalalgia and on the editorial boards of Neurology® and Headache; receives royalties from publishing Headache in Clinical Practice (Isis Medical Media, 2002), Headache in Primary Care (Isis Medical Media, 1999), Wolff's Headache (Oxford University Press, 2001, 2008), Managing Migraine: A Physician's Guide (BC Decker, 2008), and Managing Migraine: A Patient's Guide (BC Decker, 2008); has received speaker honoraria from the National Headache Foundation, the University of Oklahoma, the American Academy of Neurology, the Annenberg Foundation, Merck Serono, GlaxoSmithKline, and Coherex Medical; serves as a consultant for Allergan, Inc., Autonomic Technologies, MAP Pharmaceuticals, Inc., Neuralieve, Inc., and Novartis; receives/has received research support from AstraZeneca, Ortho McNeil, GlaxoSmithKline, Merck Serono, ProEthic Pharmaceutical, Inc., Advanced Bionics, the NIH/NIA, St. Jude Medical, the Migraine Research Foundation, and the National Headache Foundation; and holds stock options in Minster Pharmaceuticals plc. Dr. Bressman serves on scientific advisory boards for the Bachmann Strauss Dystonia and Parkinson's Foundation, the Michael J Fox Foundation for Parkinson's Research, and the Dystonia Medical Research Foundation; holds a patent re: THAP1 gene testing; and receives research support from the NIH and the Michael J Fox Foundation for Parkinson's Research.
PY - 2011/7/26
Y1 - 2011/7/26
N2 - Background: Olfactory dysfunction is an established nonmotor feature of idiopathic Parkinson disease (PD), which may precede disease onset. Olfaction is likely disturbed in patients with PD with leucine-rich repeat kinase (LRRK2) G2019S mutations, although the degree of impairment is debated. It is also unclear whether mutation carriers who have not yet manifested with PD have olfactory disturbances. Methods: Thirty-one subjects with LRRK2 G2019S mutation-related PD (PD-manifesting carriers [PD-MC]), 30 subjects with PD without mutations (PD noncarriers [PD-NC]), 28 mutation carrier family members (nonmanifesting carriers [NMC]), and 46 controls completed the University of Pennsylvania Smell Identification Test (UPSIT). Generalized estimating equations were applied to determine whether olfactory score was associated with PD and LRRK2 mutation status. Results: As expected, having PD was associated with impaired olfaction regardless of LRRK2 mutation status. More importantly, however, impaired olfaction was increased overall in LRRK2 carriers both with and without PD, though the impairment was only present in a subset of NMCs. Compared to controls, the mean score was lower among NMC (difference=-3.518, p = 0.006), MC (difference=-7.677, p < 0.0001), and idiopathic PD (PD-NC) (difference=-13.810, p < 0.0001). Olfaction was better among MC (PD-MC) than non-LRRK2 PD (PD-NC) (difference = 6.13, p = 0.0012). Group differences from the continuous analysis were maintained in dichotomous analysis stratifying at 15th percentile for age and gender. Conclusion: Olfaction is impaired in LRRK2 G2019S-mutation related PD, although less overall than other PD. Further, olfaction is impaired in a subset of LRRK2 NMC, suggesting that olfaction may be a marker for development of PD in this group, and that longitudinal studies are warranted.
AB - Background: Olfactory dysfunction is an established nonmotor feature of idiopathic Parkinson disease (PD), which may precede disease onset. Olfaction is likely disturbed in patients with PD with leucine-rich repeat kinase (LRRK2) G2019S mutations, although the degree of impairment is debated. It is also unclear whether mutation carriers who have not yet manifested with PD have olfactory disturbances. Methods: Thirty-one subjects with LRRK2 G2019S mutation-related PD (PD-manifesting carriers [PD-MC]), 30 subjects with PD without mutations (PD noncarriers [PD-NC]), 28 mutation carrier family members (nonmanifesting carriers [NMC]), and 46 controls completed the University of Pennsylvania Smell Identification Test (UPSIT). Generalized estimating equations were applied to determine whether olfactory score was associated with PD and LRRK2 mutation status. Results: As expected, having PD was associated with impaired olfaction regardless of LRRK2 mutation status. More importantly, however, impaired olfaction was increased overall in LRRK2 carriers both with and without PD, though the impairment was only present in a subset of NMCs. Compared to controls, the mean score was lower among NMC (difference=-3.518, p = 0.006), MC (difference=-7.677, p < 0.0001), and idiopathic PD (PD-NC) (difference=-13.810, p < 0.0001). Olfaction was better among MC (PD-MC) than non-LRRK2 PD (PD-NC) (difference = 6.13, p = 0.0012). Group differences from the continuous analysis were maintained in dichotomous analysis stratifying at 15th percentile for age and gender. Conclusion: Olfaction is impaired in LRRK2 G2019S-mutation related PD, although less overall than other PD. Further, olfaction is impaired in a subset of LRRK2 NMC, suggesting that olfaction may be a marker for development of PD in this group, and that longitudinal studies are warranted.
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U2 - 10.1212/WNL.0b013e318227041c
DO - 10.1212/WNL.0b013e318227041c
M3 - Article
C2 - 21753159
AN - SCOPUS:80051513364
VL - 77
SP - 319
EP - 324
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 4
ER -