Daytime alertness in Parkinson's disease: potentially dose-dependent, divergent effects by drug class

Many patients with idiopathic Parkinson's disease experience difficulties maintaining daytime alertness. Controversy exists regarding whether this reflects effects of antiparkinsonian medications, the disease itself, or other factors such as nocturnal sleep disturbances. In this study we examined the phenomenon by evaluating medicated and unmedicated Parkinson's patients with objective polysomnographic measurements of nocturnal sleep and daytime alertness. Patients (n = 63) underwent a 48-hour laboratory-based study incorporating 2 consecutive nights of overnight polysomnography and 2 days of Maintenance of Wakefulness Testing. We examined correlates of individual differences in alertness, including demographics, clinical features, nocturnal sleep variables, and class and dosage of anti-Parkinson's medications. Results indicated that, first, relative to unmediated patients, all classes of dopaminergic medications were associated with reduced daytime alertness, and this effect was not mediated by disease duration or disease severity. Second, the results showed that increasing dosages of dopamine agonists were associated with less daytime alertness, whereas higher levels of levodopa were associated with higher levels of alertness. Variables unrelated to the Maintenance of Wakefulness Test defined daytime alertness including age, sex, years with diagnosis, motor impairment score, and most nocturnal sleep variables. Deficits in objectively assessed daytime alertness in Parkinson's disease appear to be a function of both the disease and the medications and their doses used. The apparent divergent dose-dependent effects of drug class in Parkinson's disease are anticipated by basic science studies of the sleep/wake cycle under different pharmacological agents.