The Role of Amyloid in the Progression of Cognitive Impairment in PD: A Prospective Cohort Study

Objective/Rationale:             
Dementia is a frequent and devastating non-motor complication of Parkinson's disease (PD). Although loss of dopamine producing brain cells play a role in cognitive changes, persons with PD with more severe cognitive changes generally have additional loss of brain cells that produce the neurotransmitter acetylcholine.  There is increasing evidence that a subset may also have the buildup of an Alzheimer protein in the brain called amyloid (Ab) and that these persons have more rapid progression to dementia.

Project Description:             
We propose to study persons with PD with detailed clinical, cognitive and imaging at the time of study entry and repeat these assessments two years later. The imaging test battery will consist of amyloid and acetylcholine brain PET and MRI scans. The use of acetylcholine PET imaging will demonstrate how changes in activity of this neurotransmitter relate to changes in cognitive functions, such as memory and mental concentration. A key question will be whether persons with PD who not only are losing acetylcholine brain cells but also have the buildup of the Alzheimer amyloid protein have a more rapid progression with more severe cognitive decline and behavioral changes compared to persons who do not have the amyloid protein.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:                     
Positive findings in this study would establish the occurrence of amyloid protein buildup (which can be readily identified using a PET scan) as an important contributor to more rapid cognitive decline in PD.  These results would promote development of anti-amyloid therapies as an important new route to slow down the development of dementia in PD. A paradox of amyloid build-up in the brain in PD is that even relatively low levels may have a significant effect on cognitive functions offering a unique window of opportunity for early intervention.

Anticipated Outcome:          
We expect to demonstrate that a significant subset of PD subjects will have increased amyloid protein build up in the brain which is associated with more rapid cognitive and behavioral decline compared to persons who lose acetylcholine brain cells but have no evidence of amyloid activity in the brain. We expect also that amyloid PET imaging may be used as a biomarker to select appropriate candidates for future clinical intervention  trials.