rCBF was measured in 10 male and 10 female normal righthanders with an average age of 44.2 years. For the measures f1 and IS significant occipital lobe activation was produced bilaterally and for the measure IS significant left hemisphere parietal activation was produced also by a visually presented right-left discrimination cognitive activation task over and above the activation produced by a sensorimotor control task. The amount and pattern of blood flow changes were similar for both sexes. Performance of males on the cognitive task was not significantly better than that of females. However, an inverse relationship was found for males but not females between cognitive task performance and percentage increase in IS for all regions showing significant cognitive activation.
We assessed the effect of chronic long-term physostigmine in 20 patients with probable Alzheimer's disease. Initially, all patients went through a dose-finding phase and a double-blind crossover period, and were subsequently classified as physostigmine responders or nonresponders based on an a priori classification system. We then offered all patients long-term treatment with physostigmine regardless of their initial classification. Results revealed that responders spent significantly (p less than 0.0005) longer time periods on drug (36.1 +/- 4.6 months) than nonresponders (10.8 +/- 3.2). During a 2nd crossover period, 18 months into treatment, responders still demonstrated behavioral improvement, as assessed with the Sandoz Clinical Assessment-Geriatric Scale, whereas there were no behavioral changes observed in nonresponders. There were no effects on formal neuropsychological assessment. The results suggest that a subgroup of Alzheimer's patients benefits from long-term physostigmine therapy.
To assess the efficacy of oral physostigmine for the treatment of Alzheimer's disease, 20 patients were entered into a clinical trial. All patients underwent a dose-finding phase (two weeks), followed by an open trial (two weeks), and a double-blind crossover phase (two weeks drug, two weeks placebo). Extensive neuropsychological testing (Buschke Selective Reminding procedure, category generation, picture recognition, finger tapping) and measurement of systemic cholinergic parameters were measured during each of these phases. Patients were classified as physostigmine responders and nonresponders based on a priori established criteria. Using these, nine patients were found to respond to physostigmine, while 11 were classified as nonresponders. During baseline conditions, responders when compared to nonresponders were found to have higher concentrations of red blood cell (RBC) choline (Ch) and higher ratios of RBC Ch to plasma Ch. Neuropsychological tests were found to fall into one of three categories. The first group of tests were sensitive to drug effects and differentiated physostigmine responders from nonresponders; the second group was found to predict responsiveness; and the third group was neither predictive nor sensitive to drug effects.
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