Trialect

Active

Notice of Special Interest (NOSI): Sleep Disorders and Circadian Clock Disruption in Alzheimers Disease and other Dementias of Aging

National Institutes of Health

Alzheimer’s disease (AD) is a progressive, degenerative disorder of the brain and is the most common form of dementia in older adults. AD is the sixth leading cause of death in the United States. Prominent behavioral manifestations of AD include memory impairments and decline in other cognitive domains. Currently, at least 6.2 million Americans age 65 and older are living with AD.

In response to this impending public health crisis, the National Alzheimer’s Project Act (NAPA) was signed into law in 2011. As part of the strategic planning process to implement NAPA, NIH AD Research Summits identified research priorities and strategies needed to accelerate basic research and the development of effective therapies. This Notice of Special Interest (NOSI) was developed in response to recommendations from the Alzheimer’s Disease Research Summits to create new research programs aimed at understanding the integrative physiology of circadian rhythms and sleep and its impact on brain aging and the risk of AD and AD-related dementias (ADRD) at multiple levels (e.g., epigenetic, gene expression, proteomic, neuronal, network, systems) to identify new targets and approaches for AD prevention (see 2015 AD Summit: 3J; 2018 AD Summit: 5E).

An estimated 70 million people in the United States suffer from a sleep disorder. About 30 million Americans experience chronic insomnia, and approximately 18 million experience sleep apnea; however, it is estimated that fewer than 50% of those are diagnosed. Difficulties with sleep are common complaints among the aging, as more than half of older Americans report chronic sleep problems.

Individuals living with AD often exhibit sleep disturbances and circadian clock disruptions. Although this has been interpreted as a consequence of AD, there is evidence that sleep disturbances may contribute to the risk of AD. For example, it has been demonstrated that preclinical signs of AD are often associated with poor sleep quality. Moreover, Aβ accumulation in the brain predicts and exacerbates sleep disruption in humans and in animal models, and experimental manipulations to increase sleep result in decreases in Aβ deposition. Such findings provide support for interventions that improve sleep in older adults to reduce the risk of developing AD. Effective interventions exist to improve sleep, and these could be tested in AD prevention.

While it appears that there is a bidirectional relationship between chronic sleep and circadian disruption and AD pathogenesis, and previous studies have established that humans with AD and mice with Aβ pathology develop sleep and circadian dysfunction, little is known about the mechanisms involved.

The aim of this NOSI is to advance basic and clinical research on the causes and consequences of sleep deficiency and circadian clock dysfunction in AD/ADRD, and the roles of sleep and the circadian clock as modifiers of the onset and progression of neurodegeneration.

This notice applies to due dates on or after March 11, 2022 and subsequent receipt dates through November 13, 2024.

Application Due Date(s): March 11, 2022; July 8, 2022; Nov 14, 2022; March 10, 2023; July 10, 2023; Nov 13, 2023; March 11, 2024; July 9, 2024; Nov 12, 2024

NOT-AG-21-051