title: Olfactory identification in LRRK2 G2019S mutation carriers: a relevant marker?
abstract: OBJECTIVE
  Olfactory impairment is a potential marker for impending phenoconversion to Parkinson disease (PD) that may precede the development of disease by several years. Because of low specificity, it may be of greater predictive value in those with genetic mutations and its potential as a marker for developing LRRK2 PD should be evaluated.
  
  
  METHODS
  We examined olfactory identification in 126 LRRK2 G2019S mutation carriers with PD, 125 mutation carriers not manifesting PD, 126 noncarriers with idiopathic PD, 106 noncarrier family members without PD, and 35 unrelated controls. We compared olfactory performance and performed mixture modeling to identify possible subgroups of olfactory performance in LRRK2 PD and nonmanifesting carriers.
  
  
  RESULTS
  Adjusting for sex, age, cognitive score, site, and smoking history, LRRK2 PD had better olfactory scores compared to idiopathic PD (mean olfaction difference: -3.7, P < 0.001), and both LRRK2 PD and idiopathic PD had worse olfaction than controls (-12.8, -9.1, both P < 0.001). LRRK2 PD were less likely to be hyposmic than idiopathic PD (54.8% vs. 80.2%, P < 0.001). Nonmanifesting carriers and noncarrier family members did not differ. Mixture model analysis identified three classes in the LRRK2 PD and nonmanifesting carriers, suggesting that there are subgroups with poor olfactory identification in both LRRK2 PD and nonmanifesting carriers.
  
  
  CONCLUSIONS
  Therefore, olfactory identification deficit is less likely to be an obligate feature in LRRK2 PD than idiopathic PD, and while a relevant marker in some, a subset of carriers who eventually phenoconvert may proceed directly to PD without prior impaired olfaction.
authors.affiliation: Department of Neurology, Mount Sinai Beth Israel Medical Center New York City, New York ; Department of Neurology, Icahn School of Medicine at Mount Sinai New York City, New York ; Department of Neurology, Albert Einstein College of Medicine Bronx, New York.
authors.forename: Rachel
authors.initials: R
authors.lastname: Saunders-Pullman
authors.affiliation: Movement Disorders Unit, Department of Neurology, Tel-Aviv Medical Center, Sackler School of Medicine, Sagol School of Neuroscience, Tel-Aviv University Tel-Aviv, Israel.
authors.forename: Anat
authors.initials: A
authors.lastname: Mirelman
authors.affiliation: Department of Epidemiology and Social Medicine, Albert Einstein College of Medicine Bronx, New York.
authors.forename: Cuiling
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Neurology, College of Physicians and Surgeons, Columbia University New York City, New York ; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University New York City, New York.
authors.forename: Roy N
authors.initials: RN
authors.lastname: Alcalay
authors.affiliation: Department of Neurology, University of California San Francisco San Francisco, California.
authors.forename: Marta
authors.initials: M
authors.lastname: San Luciano
authors.affiliation: Department of Neurology, Mount Sinai Beth Israel Medical Center New York City, New York.
authors.forename: Robert
authors.initials: R
authors.lastname: Ortega
authors.affiliation: Department of Neurology, Mount Sinai Beth Israel Medical Center New York City, New York.
authors.forename: Deborah
authors.initials: D
authors.lastname: Raymond
authors.affiliation: Department of Neurology, College of Physicians and Surgeons, Columbia University New York City, New York ; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University New York City, New York.
authors.forename: Helen
authors.initials: H
authors.lastname: Mejia-Santana
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai New York City, New York ; Department of Genetics, Icahn School of Medicine at Mount Sinai New York City, New York.
authors.forename: Laurie
authors.initials: L
authors.lastname: Ozelius
authors.affiliation: Department of Neurology, College of Physicians and Surgeons, Columbia University New York City, New York ; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University New York City, New York.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Clark
authors.affiliation: Genetic Institute, Tel-Aviv Medical Center, Sackler School of Medicine, Sagol School of Neuroscience, Tel-Aviv University Tel-Aviv, Israel.
authors.forename: Avi
authors.initials: A
authors.lastname: Orr-Utreger
authors.affiliation: Department of Neurology, College of Physicians and Surgeons, Columbia University New York City, New York ; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University New York City, New York ; Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University New York City, New York ; Department of Psychiatry, Columbia University Medical Center New York City, New York.
authors.forename: Karen
authors.initials: K
authors.lastname: Marder
authors.affiliation: Movement Disorders Unit, Department of Neurology, Tel-Aviv Medical Center, Sackler School of Medicine, Sagol School of Neuroscience, Tel-Aviv University Tel-Aviv, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Giladi
authors.affiliation: Department of Neurology, Mount Sinai Beth Israel Medical Center New York City, New York ; Department of Neurology, Icahn School of Medicine at Mount Sinai New York City, New York.
authors.forename: Susan B
authors.initials: SB
authors.lastname: Bressman