A DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF TACRINE IN PATIENTS WITH ALZHEIMERS-DISEASE USING SPET

Background: the effect of single-dose and long-term cholinergic enhanc ement with tacrine on regional cerebral perfusion was examined in pati ents with Alzheimer's disease using single-photon emission tomography (SPET). Method: 23 patients with probable Alzheimer's disease (DSM-III -R and NINCDS-ADRDA criteria) were scanned before and after a single o ral dose of tacrine at the start of the study and again after 12 weeks of randomized, double-blind treatment with tacrine or placebo, using high resolution Tc-99m-Exametazime SPET Patients also underwent neurop sychological testing with the CAMCOG, the Mini-Mental State Examinatio n and the Rivermead Behavioural Memory Test before and after 12 weeks of treatment. Results: occipital count ratios in all regions of intere st declined by 3% over 12 weeks, indicating a progression of the disea se. Acute tacrine challenge resulted in a 16% increase in the superior frontal and a 11% decrease in the anterior temporal cortex. The acute effects of tacrine were modified by 12 weeks of treatment, particular ly in the medial frontal (cingulate) cortex where active treatment was associated with a reduced acute tacrine response. There were no chang es in cognitive function associated with active treatment. Conclusion: the study demonstrates the sensitivity of cerebral perfusion measures to changes during acute and medium-term tacrine treatment.