Understanding the Beneficial Role of Sleep in Cognitive Deficits

Note: This grant transferred to the U of California, Davis as of March 1, 2022

Cognitive deficits and sleep disruption are the two major symptoms of Alzheimer’s disease (AD). Given that sleep is necessary for cognition we will test sleep enhancement as an interventional strategy for reducing the burden of the cognitive deficit in AD, using our new and unique mouse model of sleep enhancement. We will investigate, for the first time, the mechanism by which sleep benefits memory, providing new targets for developing pharmacological and interventional strategies to treat sleep and cognitive symptoms in AD.

Our goal is to uncover the mechanism by which sleep benefits memory consolidation in Alzheimer’s disease. The two major disabling symptoms of Alzheimer’s disease are cognitive and sleep deficits. They result in the loss of patient independence and caregiver exhaustion. Sleep is necessary for optimal cognitive functioning. Therefore, we hypothesized that in Alzheimer’s disease, sleep deficits are in part responsible for the cognitive deficits and sleep enhancement can reduce the burden of the disease. First, using a mouse model of Alzheimer’s disease characterized by sleep and cognitive deficits, we are investigating the beneficial effect of sleep enhancement in memory consolidation at the behavioral level. Second, we are investigating the mechanism underlying sleep dependent memory consolidation by studying how sleep influences the neuronal mechanisms involved in memory consolidation. The lack of tools to enhance sleep in animal models has limited the study of the role of sleep in cognitive function and in Alzheimer’s disease to sleep disruption or correlative studies. We have developed a new and unique model of sleep enhancement in mice that allows us to study, for the first time, the impact of deep sleep in physiological functions and diseases. Results from this study are expected to uncover cellular and molecular mechanisms by which sleep promotes memory consolidation in Alzheimer’s disease. Successful completion of the study will open new and extended areas of investigation into the role of sleep in Alzheimer’s pathology. The long term goal is to develop new pharmacological and interventional strategies to reduce the burden of Alzheimer’s disease.