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Funded Studies

[18F]flubatine: a novel biomarker of cognition in Parkinson's disease

Objective/Rationale:
Mild cognitive impairment and dementia are frequent symptoms of moderate to advanced Parkinson’s disease (PD). Brain positron emission tomography (PET) study findings confirm post-mortem evidence that loss of the neurotransmitter acetycholine is related to cognitive impairment in PD. However, current cholinergic augmentation therapy is not always effective and should only target those PD patients who have evidence of cholinergic system impairment. This project will study the association of nicotinic acetylcholine receptors with cognition in Parkinson’s disease using a novel PET marker of cholinergic system integrity. 

Project Description:
Parkinson’s patients will undergo nicotinic acetylcholine receptor PET imaging with the radioligand [18F]flubatine and MRI on one day and extensive neuropsychological testing on another day. The degree of nicotinic receptor expression obtained with PET imaging will be correlated with the neuropsychology test results. 

Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Positive [18F]flubatine PET findings in this study would establish nicotinic receptors as an important contributor to cognitive dysfunction in Parkinson’s disease and could kindle pharmaceutical interest in pursuing these agents for Parkinson’s disease applications. 

Anticipated Outcome:
Investigators expect that lower nicotinic receptor expression is associated with impaired cognitive functioning in Parkinson’s disease. In a personalized medicine approach, the PET radioligand [18F]flubatine could serve as an important marker to identify those patients who are expected to benefit most from nicotinic receptor drug treatment.

Final Outcome

Mild cognitive impairment and dementia are common in Parkinson's disease (PD). Using brain positron emission tomography (PET), we confirmed that loss of the brain chemical acetylcholine is related to cognitive decline in PD. However, therapy that restores acetylcholine production is not always effective and should be offered to only those people with Parkinson's disease who have evidence of changes in the production of acetylcholine. In this project, we studied the association of cognition and nicotinic acetylcholine receptors (nAChR) -- proteins on the brain cell surface that detect acetylcholine -- using [18F]flubatine, a new indicator of changes in the production and use of acetylcholine in the brain. Initial results of the study showed that the increase in nAChR in a brain region called the anterior cingulate cortex was associated with improvement in working memory. Working memory is important in learning new skills, for example, those required to participate in physical therapy. [18F]flubatine could help identify those individuals who are more likely to benefit from such therapy.


Researchers

  • Martijn L.T.M. Müller, PhD

    Ann Arbor, MI United States


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