Le sommeil comme marqueur du déclin cognitif dans la maladie de Parkinson

Parkinson’s disease (PD) is a neurodegenerative disorder characterized principally by its motor symptoms. However, non motor symptoms are frequent in PD and are associated with a poorer prognosis; these include sleep disorders and cognitive impairments. Indeed, prospective studies have shown that over a 10 year period, up to 90% of PD patients will develop dementia. Therefore, identifying clinical risk factors or markers of dementia in PD is essential, notably for early diagnosis, but also to facilitate the development of preventive therapeutic approaches. There is increasing evidence for a relationship between sleep and cognition in normal and pathological aging. Electroencephalographic (EEG) events during non rapid eye movement (N REM), including sleep spindles and slow waves (SW), may contribute to brain plasticity, learning, and memory processes. However, very few studies have investigated the relationships between sleep changes and cognitive decline in PD. The objective of this thesis is to examine whether specific sleep EEG markers are associated with increased likelihood of developing dementia on prospective follow up assessment in PD patients. The first study evaluated baseline N REM sleep SW and spindle characteristics in PD patients according to their cognitive status (presence or absence of dementia) at follow up (mean 4,5 years), along with a group of healthy controls. Compared to PD patients who remained dementia free and controls, PD patients who developed dementia at follow up showed lower baseline spindle density, amplitude, and frequency. Lower spindle amplitude in posterior cortical regions was associated with poorer visuospatial abilities in demented PD patients. SW amplitude was lower in both PD groups at baseline, regardless of dementia status at follow up. The second study examined EEG spectral markers of dementia across three states of consciousness (N REM sleep, REM sleep, and wakefulness) in PD using power spectral analysis. PD patients who developed dementia at follow up showed lower N REM sleep sigma power in parietal areas compared to both PD patients who remained dementia free and controls. During REM sleep, PD patients who converted to dementia showed, at baseline, higher power in delta and theta bands and a higher EEG slowing ratio (increased slow to fast frequencies ratio) compared to PD patients who remained dementia free and controls. In both PD groups, higher slowing ratios in temporal and occipital regions during REM sleep were associated with poor performance on visuospatial tests. Finally, PD patients who later developed dementia showed lower dominant occipital frequency as well as higher delta and slowing ratio during wakefulness compared to PD patients who remained dementia free and controls. This thesis suggests that specific EEG alterations during sleep and wakefulness, mainly in posterior cortical regions, can identify PD patients who will later develop dementia. Sleep spindle activity, as well as REM sleep and wake EEG slowing, could thus serve as additional markers of cognitive decline in PD.

Keyphrases: Cognition, Parkinson's disease, Electroencephalography, Sleep spindles, Slow waves, Rapid eye movement sleep, Dementia