REM sleep behavior disorder, as assessed by questionnaire, in G2019S LRRK2 mutation PD and carriers

Abstract

Background Rapid eye movement sleep Behavior Disorder occurs with idiopathic Parkinson disease (PD), and often precedes PD. Its frequency in LRRK2-PD and utility as a pre-clinical marker has not been established. Methods 144 idiopathic PD, 142 LRRK2 G2019S mutation PD, 117 non-manifesting carriers, 93 related non-carriers, and 40 controls completed the Rapid eye movement sleep Behavior Disorder Screening Questionnaire. Results 30.6% idiopathic PD, 19.7% LRRK2-PD, 6% non-manifesting carriers, 20.4% related non-carriers, and 15% controls met cut-scores. The likelihood of abnormal scores was decreased in LRRK2-PD vs. idiopathic PD (OR=0.55, p=0.03), non-manifesting carriers vs. related non-carriers (OR=0.25, p<0.01), and PD <3 years duration, 1/19 LRRK2-PD vs. 14/41 idiopathic PD (p<0.05). Conclusions There is a lower frequency of abnormal Questionnaire scores in LRRK2-PD, especially in early LRRK2-PD, and in non-manifesting carriers. Therefore, the Rapid eye movement sleep Behavior Disorder Questionnaire is unlikely to serve as a pre-clinical marker for phenoconversion to PD.

Application of the Movement Disorder Society prodromal criteria in healthy G2019S‐LRRK2 carriers

“…In accord with earlier reports, HC demonstrated slightly more nonmotor symptoms, such as constipation and depression, compared to HNC. Previous studies reported less hyposmia and RBD in patients with AJ and non AJ LRRK2 ‐PD, as compared to idiopathic PD cases ,. Consistent with these findings, olfaction did not differ between HC and HNC whereas there was a trend for less RBD in HC than HNC.…”

The dementia-associated APOE ε4 allele is not associated with rapid eye movement sleep behavior disorder

“…and although DLB was reported to be associated with the APOE 4 allele (Kobayashi, et al, 2011,Lane, et al, 2009), our results demonstrate lack of association between the APOE 4 allele and RBD or its age at onset. These and previous results ,Saunders-Pullman, et al, 2015 further suggest that RBD may have a distinct genetic background; it is associated with GBA mutations , but unlike PD it is not associated with LRRK2 mutations ,Saunders-Pullman, et al, 2015, and unlike DLB it is not associated with the APOE 4 allele. Thus far, GBA, SCARB2, and potentially SNCA overlap between RBD, PD and DLB (Figure 1) (Bras, et al, 2014.…”

“…Conversely, mutations in LRRK2 were not associated with RBD ,Pont-Sunyer, et al, 2015,Saunders-Pullman, et al, 2015, further supporting the hypothesis that RBD has a distinct genetic background.…”

Motor and nonmotor heterogeneity of LRRK2‐related and idiopathic Parkinson's disease

“…It may be relevant that the prior reports did not perform adjusted analyses. Three groups using samples overlapping with ours have reported lower RBDSQ scores in LRRK2 G2019S PD than in iPD 15,32,33 Although not reaching statistical significance, a lower proportion of LRRK2 G2019S PD participants in our sample reported symptoms suggestive of RBD. In iPD, RBD has proven to be the strongest known risk factor for the development of PD.…”