Central anticholinergic hypersensitivity in aging.

Although neurochemical reductions in cholinergic systems have been found to occur during aging, such changes do not necessarily translate to functional deficits. The cognitive deficits of normal aging have been attributed in part to hypocholinergic function, but anticholinergic hypersensitivity in the elderly has not been systematically documented. To test the cholinergic hypothesis of aging, we investigated the effects of scopolamine on memory and attention in healthy young and elderly subjects. Treatments included intramuscular glycopyrrolate (0.0044 mg/kg) and scopolamine (0.002, 0.004, and 0.007 mg/kg) in a randomized double-blind design. The test battery included the Selective Reminding Task (SRT), Digit Span, Paired Associates Learning (PAL), Symbol Digit Modalities Test (SDMT), and the Continuous Performance Task. Elderly controls were more impaired at lower scopolamine doses than were the young on SRT, PAL, and SDMT. These results demonstrate anticholinergic hypersensitivity and are consistent with decremental changes in cholinergic status during normal aging.