Nonmotor Symptoms in LRRK2 G2019S Associated Parkinson's Disease

This is an important study that helps us understand more about the non-motor features of LRRK2-associated PD...

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0108982

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

Gaig C, Vilas D, Infante J, Sierra M, García-Gorostiaga I, Buongiorno M, Ezquerra M, Martí MJ, Valldeoriola F, Aguilar M, Calopa M, Hernandez-Vara J, Tolosa E.

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.