Sleep Disorders in Parkinsonian and Nonparkinsonian LRRK2 Mutation Carriers

Abstract

ObjectiveIn idiopathic Parkinson disease (IPD) sleep disorders are common and may antedate the onset of parkinsonism. Based on the clinical similarities between IPD and Parkinson disease associated with LRRK2 gene mutations (LRRK2-PD), we aimed to characterize sleep in parkinsonian and nonmanifesting LRRK2 mutation carriers (NMC).MethodsA comprehensive interview conducted by sleep specialists, validated sleep scales and questionnaires, and video-polysomnography followed by multiple sleep latency test (MSLT) assessed sleep in 18 LRRK2-PD (17 carrying G2019S and one R1441G mutations), 17 NMC (11 G2019S, three R1441G, three R1441C), 14 non-manifesting non-carriers (NMNC) and 19 unrelated IPD.ResultsSleep complaints were frequent in LRRK2-PD patients; 78% reported poor sleep quality, 33% sleep onset insomnia, 56% sleep fragmentation and 39% early awakening. Sleep onset insomnia correlated with depressive symptoms and poor sleep quality. In LRRK2-PD, excessive daytime sleepiness (EDS) was a complaint in 33% patients and short sleep latencies on the MSLT, which are indicative of objective EDS, were found in 71%. Sleep attacks occurred in three LRRK2-PD patients and a narcoleptic phenotype was not observed. REM sleep behavior disorder (RBD) was diagnosed in three LRRK2-PD. EDS and RBD were always reported to start after the onset of parkinsonism in LRRK2-PD. In NMC, EDS was rarely reported and RBD was absent. When compared to IPD, sleep onset insomnia was more significantly frequent, EDS was similar, and RBD was less significantly frequent and less severe in LRRK2-PD. In NMC, RBD was not detected and sleep complaints were much less frequent than in LRRK2-PD. No differences were observed in sleep between NMC and NMNC.ConclusionsSleep complaints are frequent in LRRK2-PDand show a pattern that when compared to IPD is characterized by more frequent sleep onset insomnia, similar EDS and less prominent RBD. Unlike in IPD, RBD and EDS seem to be not markers of the prodromal stage of LRRK2-PD.

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 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 .…”

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

“…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.…”

Heart rate variability in leucine‐rich repeat kinase 2‐associated Parkinson's disease

“…Our previous study, reporting on a partially overlapping sample, also noted nonmanifesting family members, regardless of the presence of the mutation, had similar UPDRS scores, constipation, and color discrimination . REM behavior disorder has also been found to be less common in LRRK2 ‐PD than iPD . Thus, the prodromal stage of LRRK2 ‐PD appears to differ from prodromal iPD.…”