Olfactory dysfunction in LRRK2 G2019S mutation carriers

R. Saunders-Pullman, K. Stanley, Cuiling Wang, M. San Luciano, V. Shanker, A. Hunt, L. Severt, D. Raymond, L. J. Ozelius, Richard B. Lipton, S. B. Bressman

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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. 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.

Original languageEnglish (US)
Pages (from-to)319-324
Number of pages6
JournalNeurology
Volume77
Issue number4
DOIs
StatePublished - Jul 26 2011

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Parkinson Disease
Mutation
Smell
Leucine
Longitudinal Studies

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Saunders-Pullman, R., Stanley, K., Wang, C., Luciano, M. S., Shanker, V., Hunt, A., ... Bressman, S. B. (2011). Olfactory dysfunction in LRRK2 G2019S mutation carriers. Neurology, 77(4), 319-324. https://doi.org/10.1212/WNL.0b013e318227041c

Olfactory dysfunction in LRRK2 G2019S mutation carriers. / Saunders-Pullman, R.; Stanley, K.; Wang, Cuiling; Luciano, M. San; Shanker, V.; Hunt, A.; Severt, L.; Raymond, D.; Ozelius, L. J.; Lipton, Richard B.; Bressman, S. B.

In: Neurology, Vol. 77, No. 4, 26.07.2011, p. 319-324.

Research output: Contribution to journalArticle

Saunders-Pullman, R, Stanley, K, Wang, C, Luciano, MS, Shanker, V, Hunt, A, Severt, L, Raymond, D, Ozelius, LJ, Lipton, RB & Bressman, SB 2011, 'Olfactory dysfunction in LRRK2 G2019S mutation carriers', Neurology, vol. 77, no. 4, pp. 319-324. https://doi.org/10.1212/WNL.0b013e318227041c
Saunders-Pullman R, Stanley K, Wang C, Luciano MS, Shanker V, Hunt A et al. Olfactory dysfunction in LRRK2 G2019S mutation carriers. Neurology. 2011 Jul 26;77(4):319-324. https://doi.org/10.1212/WNL.0b013e318227041c
Saunders-Pullman, R. ; Stanley, K. ; Wang, Cuiling ; Luciano, M. San ; Shanker, V. ; Hunt, A. ; Severt, L. ; Raymond, D. ; Ozelius, L. J. ; Lipton, Richard B. ; Bressman, S. B. / Olfactory dysfunction in LRRK2 G2019S mutation carriers. In: Neurology. 2011 ; Vol. 77, No. 4. pp. 319-324.
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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. 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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AU - Stanley, K.

AU - Wang, Cuiling

AU - Luciano, M. San

AU - Shanker, V.

AU - Hunt, A.

AU - Severt, L.

AU - Raymond, D.

AU - Ozelius, L. J.

AU - Lipton, Richard B.

AU - Bressman, S. B.

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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.

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