Association between amantadine and the onset of dementia in Parkinson's disease

Abstract

The objective of this study is to compare the occurrence of dementia among Parkinson's disease (PD) patients treated with amantadine (AM group) with those never exposed to it (NoAM group). PD dementia shares neuroanatomical and biochemical similarities with Alzheimer's disease (AD). Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist has been shown to be beneficial in AD. Memantine is a dimethyl derivative of amantadine, which also possesses NMDA receptor blocking properties. We hypothesized that amantadine could have a beneficial effect on the occurrence of PD dementia. PD patients attending the Movement Disorders Clinics in Hillel Yaffe, Asaf Harofe Medical Centers (Israel) and Pisa (Italy) were included. Taking the onset of dementia as the endpoint, survival curves for AM and NoAM patients were estimated by the Kaplan-Meier method. The study population consisted of 593 patients (age, 69.5 +/- 9.9 years; PD duration, 9.2 +/- 6.0 years; 263 patients (44%) amantadine treated). The endpoint of dementia was reached by 116 patients (20%). PD duration until dementia was significantly longer for AM patients (9.1 +/- 5.7 years) than for NoAM patients (5.9 +/- 4.6 years, P = 0.006). The duration of amantadine exposure positively correlated with PD duration until dementia (P = 0.0001). Survival analysis, taking dementia onset as endpoint, showed slower mental decline in AM patients (Log rank P = 0.0049, Wilcoxon P = 0.0024). Mini-Mental State Examination scores were significantly higher for AM patients than for the NoAM group (P = 0.01). Age of PD onset also significantly influenced the duration of PD until dementia. Amantadine use may delay the onset of dementia in PD patients and may attenuate its severity.