Determination of the cholinergic deficit in early Parkinson’s disease, using the novel PET imaging marker [18F] Fluoroethoxybenzovesamicol (FEOBV)

2016  -  Groningen, Netherlands

Organizations

University Medical Center Groningen

Project description

Parkinson’s disease (PD) is a progressive neurological disorder and is best known for its motor impairments, including rigidity, slowness of movement and tremor. However, not only the motor system is affected in Parkinson’s disease. The majority of patients experiences difficulty planning and carrying out tasks, may find it harder to concentrate in situations that divide attention or have difficulties with their memory and finding the right words. These cognitive deficits can have a great influence on the quality of life and can already be present at the start of the disease. Up to 80% of patience experiences cognitive impairment to some level within 10 years of the disease. It can eventually lead to PD dementia.
The current understanding of the underlying brain mechanisms of cognitive impairment in Parkinson’s disease is unfortunately very limited. It is known that chemical messengers in the brain, the neurotransmitters, play an important role in PD. One of these neurotransmitters that is known to play a role in the cognitive processes is acetylcholine. However, its exact role is unknown.
To get a better understanding of the role of this messenger on the cognitive deficits in PD, we will evaluate a novel PETscan marker. This recently developed PETscan marker binds to cholinergic neurons, which are directly related to cognitive symptoms, like loss of attention and planning performance. In this study we will compare the severity of this cholinergic neuron loss in several PD patientgroups, having a different level of cognitive impairment. This will provide us with insight in the progress of cholinergic neuron loss over time and its relationship with the clinical symptoms of PD related (mild) cognitive impairment or PD dementia.

Relevance to the acceleration of therapeutics for neurodegenerative diseases of aging

Until now, treatment of cognitive symptoms in Parkinson’s disease is only available for patients with Parkinson’s disease dementia. However, there is a great unmet need for those patients who experience already cognitive problems, but do not fulfill the criteria of PD related dementia.  Using this novel PETscan marker we expect to get a better insight in the start and progression of cholinergic neuron loss and its relationship to clinically apparent cognitive symptoms.  Early recognition of cholinergic neuron loss could probably lead to an earlier start of cholinergic drugs.

Anticipated outcome

The PD patients included in this study will be divided into three groups: one group with no cognitive deficits, one group with mild cognitive impairment and one group with Parkinson’s disease dementia. It is expected that the group with PD related dementia will show the greatest loss of cholinergic innervation of the cerebral cortex, whereas the patients with mild or no cognitive impairment are expected to show a much smaller or no cholinergic neuron loss in the brain.

Furthermore we expect to find a relationship between the pattern of cholinergic innervation of the cerebral cortex and the subtype of cognitive symptoms.