Study Explores Efficacy of Parkinson's Drugs

Michele Tagliati, MD

A class of drugs normally used to treat symptoms of Alzheimer's disease also is effective in treating cognitive impairment in Parkinson's disease, a progressive neurodegenerative movement disorder with no known cure, according to a recent study led by a Cedars-Sinai researcher. However, the effectiveness of the drugs may be more limited than previously suggested, and they may carry side effects, the study found.

Michele Tagliati, MD, director of the Cedars-Sinai Movement Disorders Program and professor of neurology, and his collaborators in Italy based their conclusions on extensive analysis of previous research on the efficacy and safety of cholinesterase inhibitors — chemicals whose primary effect is to block the normal breakdown of the neurotransmitter acetylcholine.

Parkinson's disease is characterized by tremor, rigidity, slowness of movement and postural instability. The disease also is frequently associated with a wide variety of non-motor symptoms, including cognitive impairment, which has a highly negative impact on quality of life. As many as 1 million Americans currently live with the disease, according to the Parkinson's Disease Foundation.

Although the depletion of dopamine is the key neurochemical impairment in Parkinson's disease, significant deficits in transmission of acetylcholine also are present and have been associated with both cognitive decline and gait dysfunction. Cholinesterase inhibitors are believed to increase the amount of acetylcholine in the brain, Tagliati said.

In their article published in the Journal of Neurology, Neurosurgery and Psychology, the investigators said their review of past studies indicated that cholinesterase inhibitors were effective in the treatment of cognitive impairment in Parkinson's patients but did not significantly reduce the risk of falls. The drugs also produced a small negative effect on resting tremor.

"We found that while cholinesterase inhibitors do help with cognitive impairment, they do not avert the risk of falls, and treatment methods should be designed bearing in mind that there is possibly a negative effect on tremor," said Tagliati, the study's principal investigator. "A surprising positive effect was the decreased mortality in patients treated with cholinesterase inhibitors, although we need to interpret this result with caution due to the limited number of studies addressing this specific point."

To reach their conclusions, the scientists searched the scientific databases MEDLINE, Web of Science, Cochrane Central Register of Controlled Trials and Scopus to identify previously published studies in which patients with Parkinson's disease were treated with cholinesterase inhibitors. Four clinical trials, with a total of 941 patients, were included in the so-called meta-analysis.

"Meta-analysis can be thought of as 'conducting research about previous research.' We combined results from different studies in order to identify patterns, sources of disagreement among those results or other interesting relationships," explained Tagliati. "We believe that it is important to apply a systematic review approach to available evidence, in order to answer important therapeutic questions and provide guidance to the treating physicians who may be puzzled by the results of multiple studies tackling the same topic in different ways."

Tagliati's Italian collaborators included researchers from the University of Molise in Campobasso, the University of Naples Federico II in Naples, the Salvatore Maugeri Foundation in Telese Terme and the University of Pisa.

Citation: Pagano G, Rengo G, Pasqualetti G, Femminella GD, Monzani F, Ferrara N, Tagliati, M. Cholinesterase inhibitors for Parkinson's disease: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry; 2014 Sep 15.