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In Pilot Study, Memantine Improved Cognition in Parkinson Disease Patients

ARTICLE IN BRIEF

Investigators reported that memory and quality-of-life improved significantly in a small trial of 20 mg memantine for patients with Parkinson disease.

MIAMI BEACH—Memantine significantly improved measures of cognition in Parkinson disease (PD) patients in a small pilot trial, investigators reported here at the World Federation of Neurology (WFN) World Congress on Parkinson's Disease and Related Disorders in December.

The primary endpoint of clinical efficacy of the 20 mg daily dose compared with placebo was improvement on the memory subscore of the Dementia Rating Scale (DRS). The investigators also used the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus).

On both the memory and quality-of-life tests, 10 of 20 patients on 20 mg memantine improved significantly compared with eight of 10 patients on placebo who completed the 24 week randomized trial; this intention-to-treat analysis had to include the two placebo patients who dropped out. Eight patients taking memantine improved on the CIBIC-Plus, and two were “minimally worse,” according to the data presented.

“Dementia is a significant problem in Parkinson disease, and there aren't adequate treatments,” said study investigator Laura Marsh, MD, executive director of the Mental Health Care Line at the Michael E. DeBakey Veterans Administration Medical Center, and professor of psychiatry at Baylor College of Medicine in Houston.

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DR. LAURA MARSH: “Dementia is a significant problem in Parkinson disease, and there arent adequate treatments.”

Dr. Marsh said that it took three years to recruit the patients, because caring for patients with PD complicated by dementia is a particular challenge for caregivers. The study was carried out while she was at Johns Hopkins medical center.

“We knew many patients would be on acetylcholinesterase inhibitors, so we stratified the study design to allow their concomitant use,” Dr. Marsh said, “and it would be more reflective of what is going on in standard practice.” Five of the 10 patients who received memantine were also taking the acetylcholinesterase blockers.

“There was a pattern of improvement across multiple areas in the drug-treated group,” Dr. Marsh said, adding that “some motor aspects improved” in addition to the cognitive benefit obtained for most patients in this small study. The memantine group also showed improvements in measures of depressive symptoms, bradykinesia, axial impairment, and activities of daily living (p< .05 for these measures).

Dr. Marsh, who has no connection to the company that makes and markets memantine, said she intends to analyze the data obtained at 14 weeks in the trial to see if there was an interim benefit.

EXPERTS COMMENT

“The reason memantine might also work in various degenerative diseases such as AD and PD is the fact that this molecule is blocking NMDA glutamate receptors, which might be very useful in those diseases sharing deregulation of the glutamatergic system,” said Erik Wolters, MD, PhD, professor of neurology at the Vrije University Medical Center in Amsterdam, the Netherlands, and chairman of the WFN research group, Parkinsonism and Related Disorders.

Ariel Deutch, PhD, professor of psychiatry and pharmacology at Vanderbilt University, added that the data are consistent with papers published in 2009 — in Lancet Neurology and Movement Disorders — on the use of memantine at the same dose. “Both showed quite modest overall improvement, which was the primary measure. The secondary measures in Laura Marsh's study offered some tentative hope for executive function, but with the small numbers we need to await replication.”

Emmanuelle Pourcher, MD, a neurologist at the Quebec Memory & Motor Skills Disorders Research Center in Quebec City, and at Laval University, has already prescribed memantine for PD patients. “In my experience, you can be successful or not in Parkinson disease with memantine. Some patients don't tolerate it,” she said, “it's all or nothing, and its unforeseeable.”

Dementia in PD disease may be heterogeneous, Dr. Pourcher said, especially in old age-onset patients in whom the typical pattern of cognitive problems is attention fluctuations, hallucinations, diurnal somnolence, and nocturnal confusion. Or, she said, it can be less typical of a Lewy body dementia and closer to an Alzheimer-like presentation with prominent memory problems and apathy.

“This may explain why some reports with memantine were less favorable than this study,” Dr. Pourcher said. Still, she added, “Memantine is worth trying in demented Parkinson disease, as some patients do respond surprisingly well.”

REFERENCES

• Aarsland D, Ballard C, Londos E, et al. Memantine in patients with Parkinson's disease dementia or dementia with Lewy bodies: a double-blind, placebo-controlled, multicentre trial. Lancet Neurol 2009; 8:613–618.
    • Leroi I, Overshott R, Burns A, et al. Randomized controlled trial of memantine in dementia associated with Parkinson's disease. Mov Dis 2009;24(8):1217–1221.