Clonidine impairs sustained attention and memory in Alzheimer's disease

We investigated the effect of the alpha2-agonist, clonidine (orally: 0.5 and 2 microg/kg), administration on parameters assessing attention and short-term recognition memory in Alzheimer's disease patients. Clonidine 2 microg/kg, but not 0.5 microg/kg, disrupted memory accuracy in delayed matching to sample test delay-dependently in nine out of 28 patients. The volumes of the hippocampus and the entorhinal cortex of those Alzheimer's disease patients who were sensitive to clonidine administration were larger than those whose performance was unaffected by clonidine. These two groups of Alzheimer's disease patients performed equally in measures of attention after placebo or clonidine administration. Clonidine 2 microg/kg disrupted attention only at levels of testing that were demanding for the individual patients. Our results suggest that the disruptive effect of clonidine on short-term memory in Alzheimer's disease patients may be mediated via the hippocampus and the entorhinal cortex. Furthermore, the deleterious effect of clonidine on effortful attention is mediated via different brain systems from those involved in the modulation of memory function.