SYDNEY, Australia — Apomorphine may represent a novel therapeutic agent to reduce the burden of cognitive impairment in patients with Parkinson's disease (PD).

Preliminary findings from a study from the United Kingdom suggests that apomorphine may reduce brain amyloid-β levels in patients with the disease.

Alison Yarnall, MRCP, from the Institute of Ageing and Health, Newcastle University, United Kingdom, presented the study findings during the 17th International Congress of Parkinson's Disease and Movement Disorders.

"Dementia is a frequent and debilitating complication of PD and recent work suggests that some of the pathology may be due to synergistic interactions between amyloid-β and α-synuclein," Dr. Yarnall told Medscape Medical News.

Can Apomorphine Protect the PD Brain?

She said the current study was prompted by a recent study in a mouse model of Alzheimer's disease, which found that mice given apomorphine injections had improved memory and reduced amyloid burden (Ann Neurol. 2011;69:248-256).

Dr. Yarnall, with principal investigator David Burn, MD, and colleagues investigated amyloid burden in postmortem brain tissue from 36 patients with PD who had received apomorphine during life for treatment of their motor complications, and 43 who had not.

Among the 36 patients who had received apomorphine, 20 were cognitively normal and 16 had cognitive impairment. Among the 43 who had not received apomorphine, 16 were cognitively normal and 27 had cognitive impairment.

The researchers found that amyloid burden was significantly reduced in persons with normal cognition who had received apomorphine compared with persons with normal cognition who had not received the drug. There was also evidence of a dose-response relationship with apomorphine; amyloid-β deposition was lower with higher apomorphine doses.

These results suggest that apomorphine "may have a modifying effect on amyloid deposition in nondemented PD cases," Dr. Yarnall said.

However, there was no significant difference in amyloid burden between patients with cognitive impairment who did and did not receive apomorphine.

"The finding that less β-amyloid did not hold true for those with cognitive impairment and apomorphine exposure is not consistent with a protective effect," Janis Miyasaki, MD, associate clinical director of Toronto Western Hospital Movement Disorder Center, Ontario, Canada, who wasn't involved in the study, told Medscape Medical News. "This could mean that there are other confounding effects responsible for the difference in β-amyloid," she said.

"However, given that many believe cognitive impairment is an inevitability given long enough survival with PD, any signal such as this should be examined carefully with a prospective, well-designed trial," Dr. Miyasaki said. "Certainly anything that can reduce cognitive impairment in our patients will allow them to be better treated for ongoing motor symptoms and also avoid the behavioral and cognitive changes that cause more caregiver strain and increase their risk for nursing home placement," she added.

"Apomorphine is an established treatment to reduce motor fluctuations in advanced Parkinson's disease and is used in this indication in Europe for more than 20 years," Werner Poewe, MD, neurologist from Innsbruck Medical University, Austria, who also wasn't involved in the study, notes in a conference statement.

This study, Dr. Poewe says, "is the first observation of the treatment's effects on amyloid burden in brain tissue from parkinsonian donors who had been clinically followed and assessed regularly during life. The findings of potentially dose-dependent effects of apomorphine on amyloid burden opens up a completely new and unexpected potential mechanism of action of apomorphine."

Dr. Yarnall cautioned that these are "preliminary" findings and said further analyses are in progress. 

"A good next research step will be to firstly perform further more complex analyses. We then aim to undertake a pilot study using apomorphine or placebo in PD participants, and determining amyloid levels antemortem with imaging and/or cerebrospinal fluid measurements," Dr. Yarnall said.

Funding for the study was provided by Parkinson's UK. The authors, Dr. Miyasaki, and Dr. Poewe have disclosed no relevant financial relationships.

17th International Congress of Parkinson's Disease and Movement Disorders. Abstract LBA-13. Presented June 18, 2013.


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