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I have not been able to resolve the question about the efficacy of Sinemet over time. It has been stated that the administration of Sinemet should be delayed as long as possible so as to defer the eventual loss of effectiveness of the drug. Question: (1) Is this loss of efficacy due to built up immunity against the drug over a span of five or so years? Or (2) the drug becomes ineffectual because of the advance of the disease so that nothing would help at that point? (3) If Sinemet is initiated at a likewise advanced stage of PD, would it be efficatious at all? I am still baffled by the complexities of this disease. And we do the best we can because we do not like the alternative!!! Michel Near where the cherry trees recently blossomed, and where some idiots have for years tried to bloom on the hill.