Deficits in episodic memory and executive functions in relation to CB1 receptor availability 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.