Metabolic abnormalities associated with mild cognitive impairment in Parkinson disease

Abstract

Objective: To use ¹⁸F-fluorodeoxyglucose (FDG) and PET to investigate changes in regional metabolism associated with mild cognitive impairment (MCI) in Parkinson disease (PD). Cognitive abnormalities are common in PD. However, little is known about the functional abnormalities that underlie the manifestations of MCI in this disorder. Methods: We used FDG PET to measure regional glucose metabolism in patients with PD with multiple-domain MCI (MD-MCI; n = 18), with single-domain MCI (SD-MCI; n = 15), and without MCI (N-MCI; n = 18). These patients were matched for age, education, disease duration, and motor disability. Maps of regional metabolism in the three groups were compared using statistical parametric mapping (SPM). We also computed the expression of a previously validated cognition-related spatial covariance pattern (PDCP) in the patient groups and in an age-matched healthy control cohort (n = 15). PDCP expression was compared across groups using analysis of variance. Results: SPM revealed decreased prefrontal and parietal metabolism (p < 0.001) in MD-MCI relative to N-MCI, as well as an increase in brainstem/cerebellar metabolism (p < 0.001) in this group. In these regions, SD-MCI occupied an intermediate position between the two other groups. PDCP expression was abnormally elevated in the N-, SD-, and MD-MCI groups (p < 0.05), increasing stepwise with worsening cognitive impairment (p < 0.01). Conclusions: Early cognitive decline in Parkinson disease as defined by mild cognitive impairment is associated with discrete regional changes and abnormal metabolic network activity. The quantification of these alterations with ¹⁸F-fluorodeoxyglucose PET may allow for the objective assessment of the progression and treatment of this disease manifestation. GLOSSARY: BA = Brodmann area; BNT = Boston Naming Test; CVLT = California Verbal Learning Test; FDG = ¹⁸F-fluorodeoxyglucose; FWHM = full width at half maximum; HVOT = Hooper Visual Organization Test; MCI = mild cognitive impairment; MD-MCI = multiple domain MCI; MMSE = Mini-Mental State Examination; PD = Parkinson disease; PDCP = PD-related cognitive pattern; SD-MCI = single domain MCI; SDMT = Symbol Digit Modality Test; SPM = statistical parametric mapping; UPDRS = Unified Parkinson9s Disease Rating Scale; VOI = volume of interest; WCST = Wisconsin Card Sorting Test.