Evaluation of symptomatic drug effects in Alzheimer's disease: strategies for prediction of efficacy in humans.

In chronic diseases such as Alzheimer's disease (AD), the arsenal of biomarkers available to determine the effectiveness of symptomatic treatment is very limited. Interpretation of the results provided in literature is cumbersome and it becomes difficult to predict their standardization to a larger patient population. Indeed, cognitive assessment alone does not appear to have sufficient predictive value of drug efficacy in early clinical development of AD treatment. In recent years, research has contributed to the emergence of new tools to assess brain activity relying on innovative technologies of imaging and electrophysiology. However, the relevance of the use of these newer markers in treatment response assessment is waiting for validation. This review shows how the early clinical assessment of symptomatic drugs could benefit from the inclusion of suitable pharmacodynamic markers. This review also emphasizes the importance of re-evaluating a step-by-step strategy in drug development.

Decreased presynaptic dopamine function in the left caudate of depressed patients with affective flattening and psychomotor retardation.

OBJECTIVE: The study assessed striatal presynaptic dopamine function in patients with different subtypes of depression. METHOD: Magnetic resonance imaging and positron emission tomography with [(18)F]fluorodopa ([(18)F]DOPA) were used to compare six depressed patients with marked affective flattening and psychomotor retardation, six depressed patients with marked impulsivity and anxiety, and 10 healthy comparison subjects. Depressed patient groups were matched for severity of depression. RESULTS: [(18)F]DOPA uptake K(i) values in the left caudate were significantly lower in patients with psychomotor retardation than in patients with high impulsivity and in comparison subjects. CONCLUSIONS: These results suggest that left caudate dopamine function differs between depressed patients with psychomotor retardation and those with impulsivity and provide direct evidence of a link between dopamine hypofunction and psychomotor retardation in depression.