There is substantial evidence that aggressive and/or agitated behavior, whether externally or self-directed is associated with low indices of serotonin function, suggesting dysfunction of the central serotonin system. Decreased functioning of central serotonin systems may lead to dysregulated and disruptive behavior in the AD patient. The technique of tryptophan depletion (TD) allows a rapid, but short-lived lowering of brain serotonin levels. TD is performed by administering an amino acid mixture which lacks tryptophan. This mixture induces liver protein synthesis, which rapidly depletes circulating tryptophan (>80% in 5 hours), which in turns depletes brain tryptophan. Eight (8) AD patients in the early stages of illness (GDS stage 2-3) will be administered a tryptophan-deficient amino acid mixture early in the morning. Their behavior will be monitored throughout that day and through tryptophan repletion until the next morning. A control (no depletion) day will also be performed. If significant behavioral changes are seen with tryptophan depletion, this will suggest that further attempts to use this technique to understand the etiology and phenomenology of behavioral disturbances in this disorder are justified. We have run eight Alzheimer's disease patients in this protocol thus far. However, we initially had some difficulty with patients tolerating the entire amino acid mixture due to a number of factors including difficulty with swallowing the large number of capsules necessary and with nausea produced by the mixture itself which led to the first 2 patients having invalid studies. In consultation with our co-investigator at the University of Arizona, we reduced the total amount of amino acid mixture by 50%, as his data indicated that the TD obtained was almost as complete as with the full mixture. This has resulted in significant improvement in tolerance. We plan to proceed with the final 2 patients using this reduced mixture.
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