The number of people living with dementia doubles every five years, creating an ever-growing health, social,
and economic catastrophe for the future. There are currently no effective treatments for dementia. Dementia
due to Alzheimers disease, Lewy Body dementia, and Parkinsons Disease dementia is associated with
degeneration of the nucleus basalis if Meynert (NBM). This results in the loss of the cholinergic supply to the
cortex, cortical atrophy, and the loss of a variety of abilities associated with that cortex. The potential to provide
symptomatic relief through the electrical stimulation of the NBM has been recognized, with early clinical trials
underway. On the other hand, the potential for NBM deep brain stimulation (DBS) to modify the course of the
disease through stimulation induced neurogenesis has not been evaluated, despite multiple lines of evidence
demonstrating stimulation induced neurogenesis in other stuctures. We have demonstrated this potential in our
preliminary data. The goal of this proposal is charcterize and optimize this potential. To this end we will
evaluate the neuroregenerative effects and cognitive improvements associated with continuous NBM
stimulation in demented and control rats and monitor for adverse effects on sleep-wake cycles and stress.
Because of the role that the NBM plays in sleep and the potential stress of always being alert and vigilant, we
will evaluate ‘activity-dependent stimulation’ as an alternative strategy to optimize the positive effects of NBM
stimulation on neurogenesis, learning, and health of the animal. The optimal parameters for disease
modification will be important for the design of future clinical trials of NBM stimulation.