Age-related impairment of coupling mechanism between neuronal activation and functional cerebral blood flow response was restored by cholinesterase inhibition: PET study with microdialysis in the awake monkey brain.

The effects of three cholinesterase inhibitors (physostigmine, E2020, and Tacrine), all of which are to be cognitive enhancers, on the functional regional cerebral blood flow (rCBF) response were studied in young (5.9+/-1.8 years old) and aged (18.0+/-3.3 years old) monkeys under awake conditions using high-resolution positron emission tomography (PET). Under control condition, vibrotactile stimulation elicited increases in the rCBF response in the contralateral somatosensory cortices of both young and aged monkeys, but the degree of increase in rCBF response was significantly lower in aged (115.8%) than that in young monkeys (139.9%). Regional cerebral metabolic rate of glucose (rCMRglc) response to the stimulation, measured using [18F]-2-fluoro-2-deoxy-Dphysostigmine) were consistent with the data obtained by microdialysis. In contrast, the cognitive enhancers did not alter rCBF response to stimulation in young monkeys. The present results demonstrated that the functional change in rCBF response to the stimulation was induced during the aging process by impairment of the coupling mechanism between the neuronal activation and rCBF response. Furthermore, the observation that cognitive enhancers partly restored the functional rCBF response suggested that the coupling mechanism might be regulated via cholinergic neuronal transmission.