PHYSOSTIGMINE RESULTS IN AN INCREASED DECREMENT IN BRAIN GLUCOSE CONSUMPTION IN ALZHEIMERS-DISEASE

The responsibility of cerebral cholinergic lesions for the weak clinic al response to cholinergic neurotransmission enhancement of Alzheimer' s disease (AD) was studied by measuring the effects of physostigmine o n glucose consumption and neuropsychological tests. Ten AD and ten age d normals (AN) were examined twice, under placebo and under maximal to lerated doss of physostigmine, in randomized order and blind fashion. Under physostigmine, both groups showed better performances in tests m easuring attention (P < 0.05-0.001) but not long-term memory, and cere bral glucose consumption was regionally modified (P < 0.0001). We obse rved a regional decrease in AD and in AN which was larger in AD, where each patient exhibited a mean metabolic decrease. With normalized val ues, AD and AN showed a similar decrease in the metabolic values of pr efrontal cortex and striatum (P = 0.0003). These findings suggest that cholinergic neurotransmission enhancement depresses glucose consumpti on and increases selective attention in similar ways in both groups, b ut to a larger extent in AD. This suggests that brain metabolism in AD over-responds to enhancement of cholinergic neurotransmission. The ob served weak response of clinical symptomatology to anticholinesterase agents does not appear to be due to the failure to enhance the activit y of the cholinergic system in AD.