Sleep and Circadian Rhythm Regulation in Early Parkinson Disease

Abstract

IMPORTANCE Sleep disturbances are recognized as a common nonmotor complaint in Parkinson disease but their etiology is poorly understood. OBJECTIVE To define the sleep and circadian phenotype of patients with early-stage Parkinson disease. DESIGN, SETTING, AND PARTICIPANTS Initial assessment of sleep characteristics in a large population-representative incident Parkinson disease cohort (N=239) at the University of Cambridge, England, followed by further comprehensive case-control sleep assessments in a subgroup of these patients (n=30) and matched controls (n=15). MAIN OUTCOMES AND MEASURES Sleep diagnoses and sleep architecture based on polysomnography studies, actigraphy assessment, and 24-hour analyses of serum cortisol, melatonin, and peripheral clock gene expression (Bmal1, Per2, and Rev-Erbα). RESULTS Subjective sleep complaints were present in almost half of newly diagnosed patients and correlated significantly with poorer quality of life. Patients with Parkinson disease exhibited increased sleep latency (P = .04), reduced sleep efficiency (P = .008), and reduced rapid eye movement sleep (P = .02). In addition, there was a sustained elevation of serum cortisol levels, reduced circulating melatonin levels, and altered Bmal1 expression in patients with Parkinson disease compared with controls. CONCLUSIONS AND RELEVANCE Sleep dysfunction seen in early Parkinson disease may reflect a more fundamental pathology in the molecular clock underlying circadian rhythms.

Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's

“…The analysis included two population‐based, incident cohort studies (Cambridgeshire Parkinson's Incidence from GP to Neurologist [CamPaIGN],17 Parkinsonism: Incidence, Cognition and Non‐motor heterogeneity in Cambridgeshire (PICNICS)14, 18; five purpose‐built biomarkers and clinical observational studies from academic centers (Harvard Biomarker Study [HBS],19, 20, 21, 22 PROfiling PARKinson's disease [PROPARK],16 and the French Drug Interaction with Genes in PD [DIGPD]); as well as two well‐phenotyped, failed phase III clinical trials with longitudinal, observational extension studies (Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism [DATATOP]15; Parkinson Research Examination of CEP‐1347 Trial/A Longitudinal Follow‐up of the PRECEPT Study Cohort [PreCEPT/PostCEPT]13. Six cohorts enrolled patients with a diagnosis of PD established according to modified UK PD Society Brain Bank diagnostic criteria.…”

A New Perspective for Parkinson’s Disease: Circadian Rhythm

“…The hypercortisolism has also been found in patients with earlystage PD. Breen et al reported that there was an elevated total serum cortisol level and half of the patients had arrhythmic cortisol profiles but with no phase shifting [74]. This phenomenon has also been verified with the saliva biopsy in PD patients.…”

“…They showed reduced melatonin production with arrhythmic expression. In addition, the cortisol level is elevated and the brain and muscle arnt-like protein-1 (Bmal1) expression is altered in PD patients when compared with controls [74]. Further, the reduced melatonin output in PD patients is significantly related to the degeneration of hypothalamic gray matter and the disease severity [75].…”

Sleep disorders in the early stage of Parkinson’s disease in untreated patients

“…Повышенная дневная сонливость также может рассматривается в качестве премотор-ного маркера развития БП [17]. Ранние изменения циркадной регуляции сна, связанные с БП, могут предшествовать двигательным расстройствам [11].…”