Post-prandial Hypotension and Sleepiness in Parkinson's Disease and Other Synucleinopathies

Excessive daytime sleepiness (EDS) is observed in 30 to 50 % of patients with Parkinson's disease (PD) patients, Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA). It is a major complain and represents a socially relevant problem as unintended episodes of sleep can also occur while driving for example. Arterial hypotension is frequently observed in patients with PD, DLB and MSA and considered as a marker of autonomic failure. Sleepiness is known to occur preferentially when patients are having arterial hypotension whatever the cause (i.e. postprandial period, administration of hypotensive medication such as dopamine agonists). We hypothesize that arterial hypotension is associated with abnormal sleepiness. We have observed this association in an on-going epidemiological survey Hyperglycaemia induced by oral glucose load - a standardized model simulating food intake during a meal - provokes arterial hypotension in the majority of Parkinson's disease patients with dysautonomia. It can be hypothesised that sleep attacks in these patients could be mediated by this fall in blood pressure.

Excessive daytime sleepiness (EDS) is observed in 30 to 50 % of patients with Parkinson's disease (PD) patients, Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA). It is a major complain and represents a socially relevant problem as unintended episodes of sleep can also occur while driving for example. The exact pathophysiology of EDS in PD, DLB and MSA has not been fully elucidated so far, although pharmacological factors (dopaminergic medications) and pathological factors (neurodegeneration of sleep-wakefulness regulatory areas) have been identified. Arterial hypotension is frequently observed in patients with PD, DLB and MSA and considered as a marker of autonomic failure. Sleepiness is known to occur preferentially when patients are having arterial hypotension whatever the cause (i.e. postprandial period, administration of hypotensive medication such as dopamine agonists). We hypothesize that arterial hypotension is associated with abnormal sleepiness. We have observed this association in an on-going epidemiological survey (COPARK Cohort of 800 PD patients, manuscript in preparation). Hyperglycaemia induced by oral glucose load - a standardized model simulating food intake during a meal - provokes arterial hypotension in the majority of Parkinson's disease patients with dysautonomia. It can be hypothesised that sleep attacks in these patients could be mediated by this fall in blood pressure.

Eligibility Criteria:
Inclusion Criteria:

* Aged 35 to 85
* Parkinson's disease patients (UKPDSBB diagnostic criteria), patients with Dementia with Lewy Bodies (DLB consortium criteria, Mc Keith et al. 2005) or patients with Multiple System Atrophy (Gilman's criteria, 2008) complaining of a post-prandial sleepiness interfering with their daily living and with orthostatic hypotension
* Stable antiparkinsonian treatments (including those for dysautonomia) for the 2 months before the study and during the entire study
* Signed written informed consent for the present study
* Social security insurance coverage

Exclusion Criteria:

* atypical or secondary parkinsonism
* patients without excessive daytime sleepiness
* inability to give a consent due to severe cognitive dysfunction
* severe depression
* Deep brain stimulation treatment
* Moderate to severe obstructive sleep apnoea/hypopnoea syndrome or other co-morbidities that could account for abnormal daytime sleepiness
* Severe primary or secondary insomnia
* Treatment with sedative medications (unless moderate and stable treatment for more than 2 months before entering the study and maintained at stable dosage during all the study)
* Diabetes mellitus
* Systolic arterial pressure at rest in seated position lower than 100 mmHg in sitting position
* Pregnancy and suckling