Divergent expression of regional metabolic topographies in Parkinson's disease and normal ageing

We have used [18F]fluorodeoxyglucose (FDG) with PET to identify regional metabolic covariance patterns associated with Parkinson's disease and normal ageing. In this study we utilized these patterns as metabolic markers to assess the relative roles of these processes in the progression of parkinsonism. We studied 37 Parkinson's disease patients and 20 normal volunteer subjects with FDG/PET to calculate regional metabolic rates for glucose. We applied the Parkinson's disease and normal ageing regional covariance patterns separately to these data to compute the expression of both these markers in each subject on an individual case basis. The measured expression of the normal ageing pattern provided an estimate of subject age, based entirely upon the FDG/PET data. The normalized difference between this metabolic estimate and chronological age (delta) was then computed, where delta = (metabolic age - real age)/(real age). We found that delta values were negative and significantly reduced in the Parkinson's disease cohort compared with normal subjects (P < 0.005) indicating a consistent underestimation of chronological age by FDG/PET in parkinsonism. In the Parkinson's disease group, delta correlated negatively with disease duration (r = -0.38, P < 0.04); extrapolation of this linear relationship to delta = 0 yielded an estimate of the mean preclinical period of 4.5 years. These findings suggest that the Parkinson's disease process is likely to be associated with a progressive disruption of the normal age-metabolism relationship, rather than with an exaggeration of the normal ageing process. Our metabolic data also suggest that the preclinical period in Parkinson's disease is of relatively short duration.