Neuroscience of Sleep and Aging

Overall Objective

Sleep is impaired in healthy aging and Alzheimer’s Disease (AD). Deficits include reduced total sleep time and sleep efficiency, reduced time in REM and slow wave sleep (SWS), and increased time in NREM1. Sleep spindles and slow waves, key sleep features associated with plasticity and cognitive function, also decline. Impairments in AD are an exacerbation of the changes seen in healthy aging. Impairments begin during pre-clinical stages of AD. Sleep impairment may increase amyloid-beta burden through multiple potential pathways including reduced glymphatic clearance, GABA dysfunction, and chronic inflammation, and may also increase tau burden and spreading. Just as sleep impairment can exacerbate AD pathophysiology, accumulation of amyloid-beta and tau interferes with sleep in early stages of AD. In cognitively healthy older adults, amyloid-beta accumulation in the prefrontal cortex is associated with impaired memory consolidation, and this relationship is mediated by a reduction in slow waves during NREM sleep. In participants with mild cognitive impairment, deficits in sleep spectral power in the delta and theta frequency bands were observed, and these features predicted reductions in overnight memory change. Tau levels have been linked to disrupted hippocampal ripples, sleep spindles, and spindle slow wave coupling. However, much remains to be understood regarding why and how sleep changes with aging and AD and the mechanism by which disrupted sleep is related to subsequent AD pathology.

Expertise to Understand Key Pathways

CPHM faculty have strength in areas that are key targets to understanding the pathways between sleep and AD pathology and cognitive dysfunction (see Figure). This includes expertise in sex hormones, influences and assessments, cognition, neuroimaging, and data science. The goal of this research thrust is to facilitate collaborations and incentivize output amongst researchers with these skills. This will be achieved by hosting planning meetings and other activities to identify goals, mechanisms for support, current limitations, and addressing gaps and opportunities.

Core team members include: