EXECUTIVE FUNCTION AND UPTAKE OF TC-99M-EXAMETAZIME SHOWN BY SINGLE-PHOTON EMISSION TOMOGRAPHY AFTER ORAL IDAZOXAN IN PROBABLE ALZHEIMER-TYPE DEMENTIA

Preliminary reports suggest improved executive function in patients wi th lobar dementia after treatment with single doses of the alpha? adre noceptor antagonist, idazoxan. The potential for use in probable Alzhe imer-type dementia prompted the present study. Fifteen patients with p robable Alzheimer-type dementia were examined twice with neuropsycholo gical measures and 14 also with single photon emission tomography (SPE T) after a single double blind oral administration of 40 mg idazoxan o r placebo in a balanced cross-over design. Brain perfusion maps were s patially transformed into standard stereotactic space and compared pix el-by-pixel. A parametric analysis was used to examine the relationshi p between the drug effect, verbal fluency and brain perfusion. Two to 3 h after idazoxan, measures of reaction time, Stroop test, category f luency and anxiety were unchanged. Verbal fluency (letter) and spatial working memory were impaired and performance on the Tower of London t est in a sub-set of patients showed a trend to impairment in the idazo xan condition. Idazoxan produced a modest relative activation in left thalamus and inferior occipital cortex, decreases occurred in inferior anterior cingulate and left insular cortex, There were significant co rrelations on both days between measures of fluency and brain perfusio n in left lateral prefrontal cortex. The reduced performance with idaz oxan was directly correlated with reduced perfusion in left lateral pr efrontal cortex, supporting an important interaction between drug and task perfomance. The imaging component of the study therefore suggeste d that activation of frontal networks is necessary for performing flue ncy tasks in Alzheimer-type dementia. Brain networks involving prefron tal cortex are the locus for the primary cognitive effects of noradren ergic drugs. The direction of the effect of any dose of agonist or ant agonist may depend critically upon the age and pathology of the experi mental subjects and the relationship between performance, noradrenergi c drive and task difficulty.