Brain's cannabinoid receptors linked to memory loss in Parkinson's disease

BackgroundThe endocannabinoid system (ECS) is important for several neurophysiological functions, including the regulation of emotions and cognitive processes. The most abundant brain cannabinoid receptor is cannabinoid receptor type 1 (CB1R). Several preclinical studies in Parkinson's disease (PD) models suggest that modulating CB1R may impact cognitive processing. However, there are very limited studies of the relation between CB1R and cognitive processing in PD patients.ObjectiveTo explore the relationship between CB1R availability and cognitive dysfunction in PD with [18F]FMPEP-d2 positron emission tomography (PET).MethodsA total of 23 individuals with PD underwent [18F]FMPEP-d2 PET to measure cerebral CB1R availability. Cognitive symptoms were evaluated using a standardized neuropsychological test battery covering various cognitive domains, such as episodic and working memory, executive functioning, language function, visuospatial function and attention, and were correlated with CB1R availability using voxel-wise regression analysis corrected for multiple comparisons using false discovery rate (FDR) at p < 0.01.ResultsPD patients with poorer performance in episodic memory tests showed lower CB1R availability, particularly in the cingulate, temporal, and visual cortices, and thalami. Also, PD patients with poorer executive functioning showed lower CB1R availability predominantly in the insulae, caudate nuclei, thalami, brainstem, and temporal cortices. No relationship was found between CB1R availability and language function, visuospatial function, or working memory capacity.ConclusionsDecreased CB1R availability in PD patients is correlated with episodic memory impairment and executive dysfunction, suggesting that the ECS has a role in the pathophysiology of cognitive symptoms in PD. Problems with Episodic Memory or Executive Functions are Related to Disturbances in Endocannabinoid System Functioning in Parkinson's DiseasePlain language summaryWhy was the study done? The endocannabinoid system (ECS) is a network that helps regulate several brain functions like learning and memory, motor control, sleep and mood. The ECS involves endocannabinoids and type 1 cannabinoid receptors (CB1R). It has been observed that the ECS is not functioning properly in many neurodegenerative diseases, including Parkinson's disease (PD). However, it is not fully understood what symptoms the ECS dysfunction causes in PD.What did the researchers do? The research team studied the relationship between brain ECS functioning and cognitive functions, such as memory, executive functioning, language function, visuospatial function and attention, in PD. The ECS functioning of the brain was evaluated with positron emission tomography (PET) which is an imaging technique that can measure different body functions in real time. [18F]FMPEP-d2 PET tracer binds to CB1R, providing information about CB1R availability in one’s brain.What did the researchers find? Twenty-three subjects with PD underwent [18F]FMPEP-d2 PET and extensive neuropsychological testing. PD patients who performed poorly in episodic memory tests or executive function tests had lower CB1R availability in related brain areas. Instead, the performance in language or visuospatial functioning tests or working memory capacity did not have a relationship with CB1R availability.What do the findings mean? PD patients with decline in episodic memory or problems with executive functions have decreased CB1R availability. The results have implications for the development of new treatments for Parkinson's disease.