title: Olfactory dysfunction in LRRK2 G2019S mutation carriers.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, Beth Israel Medical Center, 10 Union Square East, Suite 5J, New York, NY 10003, USA. rsaunder@bethisraelny.org
authors.forename: R
authors.initials: R
authors.lastname: Saunders-Pullman
authors.forename: K
authors.initials: K
authors.lastname: Stanley
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: San Luciano
authors.forename: V
authors.initials: V
authors.lastname: Shanker
authors.forename: A
authors.initials: A
authors.lastname: Hunt
authors.forename: L
authors.initials: L
authors.lastname: Severt
authors.forename: D
authors.initials: D
authors.lastname: Raymond
authors.forename: L J
authors.initials: LJ
authors.lastname: Ozelius
authors.forename: R B
authors.initials: RB
authors.lastname: Lipton
authors.forename: S B
authors.initials: SB
authors.lastname: Bressman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology*; D000857:Olfaction Disorders / Q000150:complications / Q000235:genetics* / Q000503:physiopathology*; D055696:Olfactory Perception / Q000502:physiology; D010300:Parkinson Disease / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000502:physiology*
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases