UCLA

Parkinson’s disease (PD) is the second most common neurodegenerative disease in the world, and aging individuals are at greater risk for developing it. Though PD is better known by its motor manifestations of tremor at rest, bradykinesia, and rigidity, it also encompasses a variety of non-motor symptoms (NMS). These usually impact patients’ quality of life at a similar or greater extent than the motor signs. NMS include autonomic disturbances (constipation, urinary and gastric problems), mood and neuropsychiatric symptoms (depression, anxiety, and apathy), and sleep disturbances. Sleep-related disorders are one of the most common NMS in PD, especially insomnia, excessive daytime sleepiness (EDS), and REM sleep behavior disorder (RBD). Because sleep problems are also highly prevalent in the general older adult population and constitute a public health problem, our aim was to investigate multiple clinical factors, related and unrelated to PD, as potential causes or effects of self-reported sleep problems in Parkinson’s disease patients from a population-based cohort in Central California.

We first analyzed the association of probable RBD features (pRBD), measured with a questionnaire, with PD motor and cognitive progression. With information from 716 patients at baseline, prevalence of pRBD was 21%. In adjusted Cox regression models among patients with a Postural Instability and Gait Dysfunction (PIGD) phenotype, those with pRBD progressed faster to a motor UPDRS ≥ 35 (HR= 1.9, 95% CI= 1.1; 3.3). All patients with pRBD progressed twice as fast to a MMSE score≤ 24 (HR= 2.0, 95% CI= 1.1; 3.7).

From 477 patients who completed at least one follow-up, we had information on the MOS-Sleep questionnaire to examine the cross-sectional associations of PD specific features with insomnia and EDS symptoms at an average of six years of PD duration. For 156 patients, information on a second measure was also available on average two years after the first. In adjusted linear regressions with standardized insomnia or EDS scores as outcomes (mean=0 and standard deviation=1), PIGD motor signs, worse autonomic symptoms, and complex non-motor symptoms (depression, anxiety, apathy, hallucinations and dopamine dysregulation syndrome) were associated with both scores. Yet motor UPDRS tremor sub-scores and motor complications were only associated with increase in insomnia scores, and levodopa dose was associated strongly with EDS score increase (β=0.04; 95% CI 0.01, 0.08) than with insomnia (β=0.03; 95% CI 0.00, 0.06).

We also examined the association of historic neuropsychiatric diagnoses and medication, and concurrent depression symptoms with prevalent insomnia and EDS at the same average of six years of PD duration. Average MOS-Sleep EDS score was 42.2� 23.7, and insomnia score was 30.5� 22.6 (range 0 – 100). In women, anxiety or depression diagnosis occurring 10+ years before PD contributed most strongly to insomnia scores, compared to those never diagnosed (mean difference: 13.8; 95% CI 5.5, 22.0). While in men, depression or anxiety diagnosed in prodromal or clinical stages of PD (<10 years before PD diagnosis) contributed to insomnia symptoms (8.0; 95% CI 1.8, 14.2) and to EDS (9.4; 95% CI 2.4, 16.3). Current depression treatment and symptoms were strongly associated with EDS in men more than women.

In longitudinal models, only those with lower motor or autonomic symptom scores at the first follow-up showed further increase in insomnia scores after two additional years. This suggests that there may be a saturation effect of how these PD features affect further worsening of insomnia symptoms over the course of PD. Mood symptoms (GDS scores) at the first sleep measure were not associated with worsening sleep symptoms over two years of follow-up.

Employing data from one of the largest population-based studies of PD, in which movement disorder specialists assessed patients, we confirmed evidence that pRBD features are a clinical marker for faster cognitive decline and possibly also motor progression in PD patients, the latter for patients with a PIGD subtype early in the disease. Although sleep problems in PD result from a complex interaction of lifestyle and clinical factors that can be PD-related or not, we estimated the contribution of some PD-related features to insomnia and EDS symptoms, showing that different PD features are associated with different sleep symptoms, providing insight into how sleep symptoms change over time. We also indicate evidence that mood disorders diagnosis and symptoms contribute to prevalent insomnia and EDS symptoms in PD patients, with features differing in men and women.