Memantine for Treatment of Cognitive Impairment in Patients With Parkinson's Disease and Dementia

• The primary outcomes of cognitive efficacy will be paper and pencil tests of memory, clinical global impression of change scores, and Dementia Rating Scale (DRS) memory sub-score. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  

• The secondary efficacy measures are 1)additional cognitive tests 2)psychiatric symptoms 3)safety and tolerability assessments. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  

Drug: Memantine
Active memantine and placebo, taken by mouth, will be titrated from 5mg a day to 20mg a day over 4 weeks. The subject will remain on 20mg (10mg twice a day)through week 24 unless unable to tolerate. The dose will be decreased as needed.

This is a randomized, placebo-controlled, parallel, double-blind 24-week prospective study of memantine at the dosage range 5-20 mg/day in 20 outpatients with idiopathic PD and dementia secondary to PD. Using the dosage escalation regimen approved for Alzheimer disease, subjects will start memantine or comparable placebo at 5 mg daily and advance 5 mg/week to 20 mg /day by week 4, with dosing at 10 mg bid. Subjects will undergo 7 clinical visits over the 6-month trial (Screen, Baseline/Week 0, and Weeks 4, 8, 14, 20, and 24). The dosage can be titrated downward in increments of 5 mg to a minimum dose of 5 mg/day in the event memantine is not tolerated at the scheduled dosages. This broad dose range is being used because 1)a favorable cognitive response may be evident at lower doses of memantine than recommended for AD and 2)adverse effects could emerge when typical AD dosing recommendations are used, as has been observed when treating PD patients with cholinesterase inhibitors. Subjects will remain on a stable dose of memantine/placebo after Week 8, unless precluded by adverse events. Ten subjects will be assigned to each treatment group. Randomization will be stratified according to whether subjects are taking a concomitant cholinesterase inhibitor. This will enable secondary group comparisons of treatment groups. Results from this initial small study will be used to evaluate the appropriateness of devising a larger-scale multi-site study of memantine for treatment of dementia in PD.

The proposed assessment schedule was designed to represent use of memantine in general clinical practice and to minimize the burdens to caregivers and patients, who have impaired mobility as well as cognitive function.