Noradrenergic mechanisms in age-related cognitive decline.

The alpha-2 agonist, clonidine, improved spatial working memory performance in 13/13 aged rhesus monkeys with documented memory impairments. The clonidine response was blocked by alpha-2, but not alpha-1 antagonists, and appeared to result from actions at postsynaptic alpha-2 receptors in that area of cortex most critical for spatial working memory, the principal sulcal cortex. The data indicate that noradrenergic mechanisms play an important role in the functioning of the frontal association cortex, and support the rationale for giving alpha-2 agonists to restore this function in Alzheimer's patients with profound norepinephrine loss.