Funded Studies
Objective/Rationale:
Parkinson’s disease (PD) causes well known motor symptoms of tremor, slowness and stiffness, but also leads to cognitive impairment. Research has shown that early loss of cells in a brain structure called the norepinephrine-locus ceruleus in PD corresponds with the development of cognitive deficits and is a novel target for PD therapeutics. Atomoxetine (ATM) is a specific norepinephrine reuptake inhibitor, which increases the availability of this critical neurotransmitter at the brain level. Researchers hypothesize that treatment with ATM will improve attention, set-shifting, information processing speed and working memory in cognitively impaired people with PD.
Project Description:
This is an early Phase II trial to prove the concept that ATM can improve certain aspects of cognitive function in PD. Investigators will accomplish this with a double-blind, placebo-controlled trial of ATM in 30 cognitively impaired, non-demented people with PD. They hypothesize that ATM will improve attention, set-shifting, information processing speed and working memory without compromising motor function. Thirty study subjects will be randomized to receive either ATM or placebo. A carefully designed neuropsychological test will be administered at baseline and after 10 weeks of ATM treatment.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
This trial will collect the information required for a larger safety and efficacy trial. Should ATM effectively treat PD cognitive dysfunction, it would be used to treat PD cognitive problems.
Anticipated Outcome:
The proposed work is expected to demonstrate whether ATM is worth pursuing with a larger, definitive clinical trial.
Final Outcome
The ATM-Cog trial enrolled 30 patients with Parkinson’s disease and mild cognitive impairment (PD-MCI). At baseline, the average age is 67 years, 73% are male, and 93% are non-Hispanic white. 15 were randomized to atomoxetine and 15 to placebo treatment. Complete follow-up was available on 25 of the 30 subjects (83%). Five subjects withdrew early (4 in the atomoxetine and 1 in the placebo group). Atomoxetine treatment was found to be safe in this population with no unexpected adverse events, no worsening of Parkinson’s severity, and a safety profile consistent with the labeling for this drug. Treatment with atomoxetine produced subjective, but not objective, improvements in executive functioning in Parkinson’s patients with mild cognitive impairment (Patients felt better, but performed no better on the administered tests). Lack of improvement on any neuropsychological measures suggests that atomoxetine is unlikely to enhance day to day functioning in this population. Additionally, our findings suggest that atomoxetine is not useful to treat PD-MCI.
Researchers
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Vanessa K. Hinson, MD, PhD