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Metabolic abnormalities associated with mild cognitive impairment in Parkinson disease

From the Center for Neurosciences (C.H., P.M., N.B., V.D., D.E.), The Feinstein Institute for Medical Research, North Shore–Long Island Jewish Health System, New York; and the Departments of Neurology and Medicine (C.H., N.B., V.D., D.E.) and Psychiatry (P.M., K.P.), North Shore University Hospital and New York University School of Medicine, New York.

Address correspondence and reprint requests to Dr. David Eidelberg, Center for Neurosciences, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, 350 Community Drive, Manhasset, NY, 11030

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 Parkinson's Disease Rating Scale; VOI = volume of interest; WCST = Wisconsin Card Sorting Test.

david1{at}nshs.edu

e-Pub ahead of print on March 26, 2008, at www.neurology.org.

Supported by NIH National Institute of Neurological Disorders and Stroke R01 35069 (D.E.) and the General Clinical Research Center at the North Shore-Long Island Jewish Health System (NIH RR MO1 018535).

Disclosure: The authors report no conflicts of interest.

Received July 2, 2007. Accepted in final form November 2, 2007.