Hypermetabolism in the cerebellum and brainstem and cortical hypometabolism are independently associated with cognitive impairment in Parkinson's disease.

Abstract

Cognitive impairment (CI) in Parkinson's disease (PD) is associated with a widespread reduction in cortical glucose metabolism and relative increases in the cerebellum and brainstem as measured using ¹⁸F-fluorodesoxyglucose (FDG) PET. We separately analysed CI-related hypermetabolism and hypometabolism in comparison with neuropsychological test performance and investigated whether increased FDG uptake is a true feature of the disease or a normalization effect. The study included 29 subjects (12 patients with PD, 10 patients with PD dementia and 7 healthy controls") who underwent FDG PET and comprehensive neuropsychological testing. Test performance across various cognitive domains was summarized in a cognitive staging score. Metabolic indices reflecting associated changes in regional cerebral glucose metabolism (rCGM) were calculated: index^(-) for CI-related hypometabolism, and index⁽⁺⁾ for CI-related hypermetabolism. We tested whether index⁽⁺⁾ offered additional value in predicting the severity of CI in multiple regression analysis. At higher stages of CI, increased rCGM was found in the posterior cerebellar vermis and pons, associated with impaired attention, executive function and memory. Reduced rCGM was found in various cortical regions in agreement with the literature. In multiple regression analysis, both indices independently predicted the severity of CI with a whole-model R² of 0.68 (index^(-), p = 0.0006; index⁽⁺⁾, p = 0.013), confirmed by alternative analyses combining different reference tissues in the multiple regression. We found CI-related hypermetabolism in cerebellar regions that are known to be involved in several cognitive functions and in the pons. These alterations may represent compensatory activation of cognitive networks including cerebropontocerebellar tracts.