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. 2014 Oct 17;9(10):e108982.
doi: 10.1371/journal.pone.0108982. eCollection 2014.

Nonmotor symptoms in LRRK2 G2019S associated Parkinson's disease

Carles Gaig  1 , Dolores Vilas  2 , Jon Infante  3 , María Sierra  3 , Inés García-Gorostiaga  4 , Mariateresa Buongiorno  5 , Mario Ezquerra  1 , Maria José Martí  1 , Francesc Valldeoriola  1 , Miquel Aguilar  6 , Matilde Calopa  7 , Jorge Hernandez-Vara  8 , Eduardo Tolosa  1
Affiliations

Nonmotor symptoms in LRRK2 G2019S associated Parkinson's disease

Carles Gaig et al. PLoS One. .

Abstract

Background: Idiopathic Parkinson's disease (IPD) and LRRK2-associated PD (LRRK2-PD) might be expected to differ clinically since the neuropathological substrate of LRRK2-PD is heterogeneous. The range and severity of extra-nigral nonmotor features associated with LRRK2 mutations is also not well-defined.

Objective: To evaluate the prevalence and time of onset of nonmotor symptoms (NMS) in LRRK2-PD patients.

Methods: The presence of hyposmia and of neuropsychiatric, dysautonomic and sleep disturbances was assessed in 33 LRRK2-G2019S-PD patients by standardized questionnaires and validated scales. Thirty-three IPD patients, matched for age, gender, duration of parkinsonism and disease severity and 33 healthy subjects were also evaluated.

Results: University of Pennsylvania Smell Identification Test (UPSIT) scores in LRRK2-G2019S-PD were higher than those in IPD (23.5±6.8 vs 18.4±6.0; p = 0.002), and hyposmia was less frequent in G2019S carriers than in IPD (39.4% vs 75.8%; p = 0.01). UPSIT scores were significantly higher in females than in males in LRRK2-PD patients (26.9±4.7 vs 19.4±6.8; p<0.01). The frequency of sleep and neuropsychiatric disturbances and of dysautonomic symptoms in LRRK2-G2019S-PD was not significantly different from that in IPD. Hyposmia, depression, constipation and excessive daytime sleepiness, were reported to occur before the onset of classical motor symptoms in more than 40% of LRRK2-PD patients in whom these symptoms were present at the time of examination.

Conclusion: Neuropsychiatric, dysautonomic and sleep disturbances occur as frequently in patients with LRRK2-G2019S-PD as in IPD but smell loss was less frequent in LRRK2-PD. Like in IPD, disturbances such as hyposmia, depression, constipation and excessive daytime sleepiness may antedate the onset of classical motor symptoms in LRRK2-G2019S-PD.

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Conflict of interest statement

Competing Interests: Dr. Tolosa received honoraria for consultancy from Novartis, TEVA, Boehringer Ingelheim, UCB, Solvay, Lundbeck, and TEVA, and he received funding for research from Spaniard Network for Research on neurodegenerative Disorders (CIBERNED)- instituto Carlos III (ISCIII), The Michael J. Fox Foundation for Parkinson’s Research (MJFF), and Fondo de Investigaciones Sanitarias de la Seguridad Social (FISS). Dr. Infante receives research support from the Fondo de Investigación Sanitaria-ISCIII (PI11/00228) and from “Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas” (CIBERNED) (CB06/05/0037). Dr. Sierra receives research support from the Institute for Formation and Research from the Marqués de Valdecilla Foundation-IFIMAV (WLA 04/11) and from “Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas” (CIBERNED) (CB06/05/0037). Dr. Ezquerra was supported by a Miguel Servet contract of the Instituto de Salud Carlos III (ISCIII). Dr. Valldeoriola has received honoraria from Medtronic Ibérica, Boston Scientific, Abbvie Pharmaceutiocals and UCB pharma for lectures and courses. Dr. Gaig, Dr. Vilas, Dr. Buongiorno, Dr. Martí, Dr. García- Gorostiaga, Dr. Aguilar, Dr. Calopa, and Dr. Hernandez-Vara report no disclosures. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. University of Pennsylvania Smell Identification Test (UPSIT) scores.
UPSIT scores in LRRK2 G2019S Parkinson’s disease patients, idiopathic Parkinson’s disease patients and healthy controls (Figure 1.A). UPSIT score in each group separated by sex (Figure 1.B). Circles represent individual values, while the bar refers to the mean UPSIT score in each group. IPD: idiopathic Parkinson’s disease; LRRK2-PD: LRRK2 associated Parkinson’s disease, HS: healthy subjects.
See this image and copyright information in PMC

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