Olfactory dysfunction in LRRK2 G2019S mutation carriers

Department of Neurology, Beth Israel Medical Center, 10 Union Square East, Suite 5J, New York, NY 10003, USA.
Neurology (Impact Factor: 8.29). 07/2011; 77(4):319-24. DOI: 10.1212/WNL.0b013e318227041c
Source: PubMed


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.
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.
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.
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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Available from: Richard Lipton, Dec 12, 2013
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    • "The aim of this study was to determine whether o-α-syn is suitable biomarker for detecting PD at the early stages of the disease. Recently, abnormal PET changes and olfactory dysfunction were reported in LRRK2-H (Nandhagopal et al., 2008; Ruiz-Martínez et al., 2011; Saunders-Pullman et al., 2011). Therefore, healthy family members with LRRK2 mutations are an excellent population for validating surrogate biomarkers for early stages of PD. "
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    • "LRRK2 p.G2019S clinical features compared with iPD in literature are contradictory. Overall, the clinical presentation of iPD and LRRK2 parkinsonism are similar (Aasly et al., 2005; Gosal et al., 2005; Healy et al., 2008; Hulihan et al., 2008; Ishihara et al., 2006; Lesage et al., 2005; Saunders-Pullman et al., 2011). Pilot studies suggest some disparities in terms of motor and non-motor dysfunction. "
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