MEASURING THE RATE OF PROGRESSION AND ESTIMATING THE PRECLINICAL PERIOD OF PARKINSONS-DISEASE WITH [F-18] DOPA PET

Objectives-To measure the rate of progression in striatal [F-18]dopa m etabolism in a large group (n=32) of patients with Parkinson's disease , to estimate the average duration of preclinical period, and to exami ne the influence of the PET method on the assessment of rate of progre ssion and preclinical period. Methods-Thirty two patients with Parkins on's disease (mean age 58 (SD 13) years, mean duration 39 (SD 33) mont hs) were assessed with [F-18]dopa PET and UPDRS scoring on two occasio ns a mean of 18 (SD 6) months apart. PET data were sampled with separa te caudate and putamen and total striatal regions of interest, and bot h graphical (Ki) and ratio methods of analysis. Results - The mean ann ual rate of deterioration in [F-18]dopa uptake varied according to str ucture and method of analysis, with putamen Ki showing the most rapid mean rate of progression (4.7% of normal mean per year). The group sho wed a significant deterioration (p<0.0004, paired two tailed t test) i n UPDRS and in the putamen (p=0.008) and total striatal (p=0.012) [F-1 8]dopa uptake measured using a graphical analysis, but no significant change in caudate or putamen uptake measured by a ratio approach. A st udy of sensitivity confirmed that putamen Ki was the most sensitive me asure of disease progression, caudate ratio the least. Symptom onset i n Parkinson's disease was estimated at a mean putamen [F-18]dopa uptak e (Ki) of 75% of normal and a mean caudate [F-18]dopa uptake (Ki) of 9 1% of normal. Conclusions-Estimation of mean rate of progression varie s according to the sensitivity of a functional imaging method to clini cal severity. Sensitivity and reproducibility of method must be consid ered when designing studies of disease progression and neuroprotection . The mean preclinical period in Parkinson's disease is unlikely to be longer than seven years.