Jenny Ceccarini1,2, Cindy Casteels3,4, Rawaha Ahmad3,4, Melissa Crabbé3,4, Laura Van de Vliet5,6, Heleen Vanhaute3,4,5, Mathieu Vandenbulcke5,6, Wim Vandenberghe6,7, Koen Van Laere3,4. 1. Nuclear Medicine and Molecular Imaging, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. jenny.ceccarini@uzleuven.be. 2. Department of Imaging and Pathology, KU Leuven, Leuven, Belgium. jenny.ceccarini@uzleuven.be. 3. Nuclear Medicine and Molecular Imaging, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. 4. Department of Imaging and Pathology, KU Leuven, Leuven, Belgium. 5. Department of Old Age Psychiatry, University Psychiatric Centre, KU Leuven, Leuven, Belgium. 6. Department of Neurosciences, KU Leuven, Leuven, Belgium. 7. Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
Abstract
PURPOSE: The endocannabinoid system plays a regulatory role in a number of physiological functions, including motor control but also mood, emotion, and cognition. A number of preclinical studies in Parkinson's disease (PD) models demonstrated that modulating the type 1 cannabinoid receptor (CB1R) may improve motor symptoms and components of cognitive processing. However, the relation between CB1R, cognitive decline and behavioral symptoms has not been investigated in PD patients so far. The aim of this study was to examine whether CB1R availability is associated with measures of cognitive and behavioral function in PD patients. METHODS: Thirty-eight PD patients and ten age- and gender-matched controls underwent a [18F]MK-9470 PET scan to assess CB1R availability, as well as volumetric MR imaging. Neuropsychological symptoms were evaluated using an extensive cognitive and behavioral battery covering the five cognitive domains, depression, anxiety, apathy, and psychiatric complications, and were correlated to CB1R availability using vowel-wise regression analysis (P < 0.05, corrected for familywise error). RESULTS: PD patients with poorer performance in episodic memory, executive functioning, speed and mental flexibility (range P 0.003-0.03) showed lower CB1R availability in predominantly the midcingulate cortex and middle to superior frontal gyrus (Tpeak-level > 4.0). Also, PD patients with more severe visuospatial dysfunction showed decreased CB1R availability in the precuneus, midcingulate, supplementary motor cortex, inferior orbitofrontal gyrus and thalamus (Tpeak-level = 5.5). These correlations were not related to cortical gray matter atrophy. No relationship was found between CB1R availability and mood or behavioral symptom scores. CONCLUSIONS: Decreased CB1R availability in the prefrontal and midcingulate cortex in PD patients is strongly correlated with disturbances in executive functioning, episodic memory, and visuospatial functioning. Further investigation of regional CB1R expression in groups of PD patients with mild cognitive impairment or dementia is warranted in order to further investigate the role of CB1R expression in different levels of cognitive impairment in PD.
PURPOSE: The endocannabinoid system plays a regulatory role in a number of physiological functions, including motor control but also mood, emotion, and cognition. A number of preclinical studies in Parkinson's disease (PD) models demonstrated that modulating the type 1 cannabinoid receptor (CB1R) may improve motor symptoms and components of cognitive processing. However, the relation between CB1R, cognitive decline and behavioral symptoms has not been investigated in PDpatients so far. The aim of this study was to examine whether CB1R availability is associated with measures of cognitive and behavioral function in PDpatients. METHODS: Thirty-eight PDpatients and ten age- and gender-matched controls underwent a [18F]MK-9470 PET scan to assess CB1R availability, as well as volumetric MR imaging. Neuropsychological symptoms were evaluated using an extensive cognitive and behavioral battery covering the five cognitive domains, depression, anxiety, apathy, and psychiatric complications, and were correlated to CB1R availability using vowel-wise regression analysis (P < 0.05, corrected for familywise error). RESULTS:PDpatients with poorer performance in episodic memory, executive functioning, speed and mental flexibility (range P 0.003-0.03) showed lower CB1R availability in predominantly the midcingulate cortex and middle to superior frontal gyrus (Tpeak-level > 4.0). Also, PDpatients with more severe visuospatial dysfunction showed decreased CB1R availability in the precuneus, midcingulate, supplementary motor cortex, inferior orbitofrontal gyrus and thalamus (Tpeak-level = 5.5). These correlations were not related to cortical gray matter atrophy. No relationship was found between CB1R availability and mood or behavioral symptom scores. CONCLUSIONS: Decreased CB1R availability in the prefrontal and midcingulate cortex in PDpatients is strongly correlated with disturbances in executive functioning, episodic memory, and visuospatial functioning. Further investigation of regional CB1R expression in groups of PDpatients with mild cognitive impairment or dementia is warranted in order to further investigate the role of CB1R expression in different levels of cognitive impairment in PD.
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