Study Links Alzheimer’s Onset to Sleep Disruption and Degeneration of Key Brain Region

Reviewed by: Sharyn Rossi, PhD, BrightFocus Foundation 

Scientists have long been aware that people with Alzheimer’s disease often struggle to sleep. Now, researchers are investigating whether sleep patterns appear before the onset of symptoms and if monitoring sleep can help identify those who are at risk for Alzheimer’s. 

A new BrightFocus Foundation-funded Alzheimer’s Disease Research study is helping to answer that question. Researchers found that damage to a brain area called the locus coeruleus is closely associated with sleep disruption prior to cognitive decline in Alzheimer’s disease. They believe their discoveries could inspire new methods for monitoring sleep patterns in healthy people in the hopes of better identifying those who face a high risk of Alzheimer’s. 

The research team, led by Alzheimer’s Disease Research-funded investigator Maxime Van Egroo, PhD, during his postdoctoral fellowship under Heidi Jacobs, PhD, at Maastricht University in the Netherlands, used data from a previous long-term study on aging and memory. The study results were published in the journal Annals of Neurology. 

The team targeted its investigation toward the locus coeruleus, a brain structure known to play a role in the sleep-wake cycle and Alzheimer’s. Before Alzheimer’s symptoms appear, a person may experience disrupted rest-activity “fragmentation,” which is an inability to stay asleep or awake for long periods of time. This fine balance between rest and activity is partially controlled by the locus coeruleus, which regulates the release of norepinephrine, an important brain hormone for sleep.   

Dr. Van Egroo and his colleagues discovered fragmented sleep patterns in participants with Alzheimer’s an average of seven years prior to death, when many participants displayed mild to no cognitive symptoms. This demonstrates a novel association between degeneration of the locus coeruleus and early clinical signs of Alzheimer’s disease.  

Previous studies point to the locus coeruleus as one of the first sites to display accumulation of the tau protein—a hallmark of Alzheimer’s—and brain degeneration. Earlier BrightFocus Foundation-funded research found a link between high plasma levels of tau, locus coeruleus degeneration, and disrupted sleep in cognitively unimpaired people. 

Yet, the association between degeneration of the locus coeruleus and patterns of rest and wakefulness remains unclear—a mystery the researchers set out to unravel. 

Linking Fragmented Sleep to Alzheimer’s Brain Changes 

The research team collected data from the Rush Memory and Aging Project, an observational study of 388 volunteers aged 60 and older who underwent yearly medical testing and donated their brains for further research after death. Researchers looked at their performance on cognitive tests and measurements of each participant’s 24-hour rest-activity patterns. Participants wore a small device that tracked their daily movements, indicating the amount of time each person spent resting or awake.  

Brain studies looked for signs of degeneration in the locus coeruleus —commonly observed as a loss of tissue pigment—and the presence of Alzheimer’s tau tangles and amyloid plaques.  

Upon enrollment in the study, most participants were diagnosed as cognitively unimpaired, and the rest were deemed to have mild cognitive impairment. The final clinical diagnoses after death showed that nearly 37% of participants had Alzheimer’s dementia, 25% had mild cognitive impairment, and the rest were unimpaired. 

The researchers discovered that 25% of participants showed degeneration (loss of pigment) of their locus coeruleus, appearing more severe in those diagnosed with Alzheimer’s. These participants showed a more fragmented rest-activity pattern previously observed in people with Alzheimer’s. Study results also showed a direct link between fragmented sleep patterns and locus coeruleus degeneration, which was associated with cognitive decline.  

These discoveries about sleep and Alzheimer’s disease demonstrate that monitoring rest and activity patterns in the elderly can serve as a pre-symptomatic indicator for locus coeruleus degeneration and future cognitive decline. The authors conclude that these results support a strategy for monitoring patterns of rest and activity in older people.  

Doing so, the authors suggested, could help clinicians identify people most at risk of Alzheimer’s and guide the implementation of preventive strategies. Everyday activity monitors may be used by doctors as notification devices for further diagnostic testing – as they currently are used for changes in heart function and blood pressure.   

Some limitations of the study include imaging resolution and the small size of the locus coeruleus. The authors also highlighted a need for a more specific approach to measuring locus coeruleus degeneration. 

Learn more about BrightFocus Alzheimer’s Disease Research projects like this below: 

• The Locus Coeruleus and Memory Selectivity in Aging and Alzheimer's Disease  

• Does Pathology in Locus Coeruleus Trigger Alzheimer’s Disease?  

• Improving Sleep to Prevent Alzheimer's Disease 

Additional Resources: 

• Sleeping Pill Found to Possibly Slow or Stop Alzheimer’s Disease  

• What Is “Healthy” Sleep and Why Is It Important for Alzheimer’s and Other Diseases? 

• Sleep Apnea and Dementia 

• What’s the Connection Between Daytime Napping and Alzheimer’s? 

About BrightFocus Foundation

BrightFocus Foundation is a premier global nonprofit funder of research to defeat Alzheimer’s, macular degeneration, and glaucoma. Through its flagship research programs — Alzheimer’s Disease Research, National Glaucoma Research, and Macular Degeneration Research — the Foundation has awarded nearly $300 million in groundbreaking research funding over the past 50 years and shares the latest research findings, expert information, and resources to empower the millions impacted by these devastating diseases. Learn more at brightfocus.org.     

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