Intermittent Stimulation of the Basal Forebrain Improves Working Memory in Aged Nonhuman Primates

Introduction: Aging and dementias feature parallel declines in the basal forebrain and cognitive capacity. The aged primate has declines in cognition analogous to those in humans. Beta-amyloid plaques form with age although the presence of neurofibrillary tangles composed of tau is more rare and appears shifted to a later age. We investigated whether deep brain stimulation of the nucleus basalis of Meynert in senescent monkeys could halt or reverse cognitive decline.

Methods: Here, we tested the potential of one-hour daily intermittent basal forebrain stimulation to restore cognitive performance in aged male and female monkeys.

Results: Stimulation improved working memory in weeks. In an ensuing three month test with stimulation halted, improvements were retained. With additional stimulation, performance remained above baseline throughout the 15 month duration of the intervention.

Conclusion : Parallel studies with a cholinesterase inhibitor did not produce lasting improvements in behavior. Brain stimulation led to acute increases in tissue plasminogen activator levels in cerebrospinal fluid, and long-term increases in PET measures of glucose utilization. Intermittent basal forebrain stimulation triggers components of neurotrophic signaling and leads to improved brain metabolism and better performance in working memory in senescent monkeys.