Basal forebrain activation improves working memory in senescent monkeys

Abstract

Aging and some dementias feature parallel declines in the basal forebrain and cognitive capacity. Here, we tested the potential of one-hour daily intermittent basal forebrain stimulation to restore cognitive performance in aged male and female monkeys. Stimulation improved working memory in weeks, with performance remaining above study entry through the 15 month duration of the intervention. Effects persisted for at least 12 weeks after stimulation ceased. Parallel studies with a cholinesterase inhibitor did not produce lasting improvements in behavior. Brain stimulation led to immediate increases in tissue plasminogen activator levels in cerebrospinal fluid, and long-term increases in PET measures of glucose utilization. Intermittent basal forebrain stimulation thus triggers key components of neurotrophic signaling and leads to improved brain metabolism and better performance in working memory in senescent monkeys.