More Than Rapid Eye Movement Sleep Behavior Disorder: Sleep Differences in Parkinson’s Disease LRRK2 and GBA Genotypes

Abstract

Objectives: Sleep disorders can significantly worsen the quality of life in Parkinson’s disease (PD). Variants in <i>LRRK2</i> and <i>GBA1</i>, the most common genetic contributors to PD, may lead to different clinical features, including more REM sleep behavior disorder (RBD) in PD associated with <i>GBA1</i> mutations (<i>GBA</i> PD). However, there is a dearth of information about differences in non-RBD sleep disorders among these genetic subgroups. Methods: Seventy-nine participants with PD (18 <i>LRRK2 G2019S</i> carriers with PD [<i>LRRK2</i> PD], 22 <i>GBA1</i> [<i>GBA</i> PD], 2 <i>LRRK2 GBA</i> PD and 37 idiopathic PD [iPD]) underwent actigraphy (Actiwatch-2) for 1 week. Subjective sleep quality was assessed using questionnaires. Results: <i>LRRK2</i> PD participants demonstrated better sleep actigraphy, including reduced wake after sleep onset (-25 minutes; <i>p</i><0.001) and higher sleep efficiency (6.3%; <i>p</i>=0.015), than iPD and <i>GBA</i> PD in models adjusted for age, age at disease onset, and gender. While sleep onset times did not differ between groups, all groups had mean sleep onset times after 11:00 PM, and did not demonstrate phase advancement. Sleep questionnaires showed only an increased prevalence of RBD in <i>GBA</i> PD and iPD. Conclusions: <i>LRRK2</i> PD is associated with less fragmented sleep than <i>GBA</i> PD and iPD, suggesting that despite similar objective sleep complaints, genotypic sleep differences extend beyond RBD. These differences support the need for personalized and genotypic approaches to sleep disturbances in PD. The absence of phase advancement in all groups suggests that lighting interventions to improve sleep disorders should be considered for the morning rather than later in the day.