CHOLINERGIC NEUROTRANSMISSION HAS DIFFERENT EFFECTS ON CEREBRAL GLUCOSE CONSUMPTION AND BLOOD-FLOW IN YOUNG NORMALS, AGED NORMALS, AND ALZHEIMERS-DISEASE PATIENTS

Cerebral blood flow (CBF) and glucose consumption (GC) are both tracer s of brain metabolic activity used to image the human brain in vivo. T o know if both tracers reacted in the same manner when brain cholinerg ic neurotransmission was activated, CBF and GC were measured in young normals (YN), aged normals (AN), and Alzheimer's Disease patients (AD) using positron emission tomography (PET), H-2 O-15, F-18-FDG. Each su bject was studied twice, under placebo and physostigmine, in randomize d order and blind fashion using the maximal tolerated dose of physosti gmine individually determined. Under physostigmine CBF increased signi ficantly (P = 0.0007) in posterior regions of the cerebral cortex and in the subcortical structures. Inversely, GC was decreased significant ly in most regions. The largest decrease was seen in the prefrontal re gion of the cerebral cortex (P < 0.0001). Significant regional decreas es were registered in all three groups of subjects, but were larger in AD than in controls. Looking at the absolute values of prefrontal cor tex metabolism we found no correlation (r = 0.04) between the response s of CBF and GC. After normalization of the regional values for the me an we found a significant positive correlation between the responses o f CBF and GC (r = 0.71, P < 0.0001). These findings suggest two compon ents in the CBF response to physostigmine: one metabolic, depressive, and regional which follows the GC response; and one vascular, larger, diffuse, and opposite in direction to the metabolic component. These r esults have implications for the interpretation of CBF values as trace r of brain metabolic activity when brain cholinergic neurotransmission is manipulated. (C) 1997 Academic Press.