Understanding the Connection Between Circadian Rhythm and Alzheimer’s Disease

According to the Alzheimer’s Association, more than six million Americans are living with Alzheimer’s disease as of 2022; by 2050, this number is projected to rise to nearly 13 million. In 2022, Alzheimer’s disease and other causes of dementia will cost the nation $321 billion; by 2050, these costs could reach nearly $1 trillion.

The increasingly high prevalence and the consequent social and economic impact of Alzheimer’s disease demonstrate the importance of research efforts surrounding modifiable risk factors and Alzheimer's prevention strategies.

Recently, researchers have uncovered a connection between circadian rhythm and Alzheimer's disease. Below, we take a closer look into research surrounding this relationship and discuss sleep disturbances as an emerging target for Alzheimer’s disease prevention.

The Relationship Between Circadian Rhythm and Alzheimer’s Disease

Circadian rhythm is the natural cycle of physical, mental, and behavioral changes that our bodies go through in a 24-hour cycle. Circadian rhythms can affect sleep-wake cycles, hormonal activity, body temperature, eating and digestion, and other functions. You can think of this as part of your biological clock that helps you fall asleep at night and wake up in the morning. 

It is widely known that sleep-wake and circadian rhythm disruption is common in Alzheimer’s disease patients—these changes occur early in the disease course and may even precede the development of cognitive symptoms. However, increasing evidence suggests that these disturbances may also contribute to the development and progression of Alzheimer’s and other neurodegenerative diseases. 

Research Linking Circadian Rhythm and Alzheimer’s Disease

The etiopathogenesis of circadian rhythm disturbances and Alzheimer’s disease share several features that suggest they may be a mutually dependent pathway. Pathological mechanisms, such as amyloid production and clearance, neuroinflammation, and oxidative stress, can be linked to circadian rhythm disruption, sleep deprivation, and Alzheimer’s disease. Here is what research tells us about the connection between circadian rhythm and Alzheimer’s disease:

• Sleep-wake cycles regulate Alzheimer’s disease pathology: Many studies have shown that sleep-wake cycles may regulate the level of beta-amyloid proteins—one of the primary neuropathological hallmarks of Alzheimer’s disease. Clearance of this protein is essential for a healthy neuronal microenvironment. The accumulation of this protein (known as beta-amyloid plaques) is believed to accelerate the development and progression of Alzheimer’s disease. A 2022 study demonstrated that the immune cells responsible for clearing this protein from the brain follow a 24-hour circadian oscillation. This suggests that disruptions in the circadian rhythm may affect the clearance of these harmful plaques, and, consequently, the accumulation of beta-amyloid.
• Sleep deprivation exacerbates Alzheimer’s pathology: A 2022 study found that chronic fragmentation of the sleep-wake rhythms increased hippocampal beta-amyloid levels and neuroinflammation in Alzheimer's disease mouse models. These findings suggest disruption of daily-sleep wake cycles may increase the risk of developing Alzheimer’s disease. Similar findings have been demonstrated in human studies. In a small study of humans, researchers found that just one night of sleep deprivation resulted in a significant increase in beta-amyloid burden in the right hippocampus and thalamus.
• Insufficient sleep may increase dementia risk: In a 2021 study, researchers at Harvard Medical School found that those who slept fewer than five hours per night were twice as likely to develop dementia compared to those who slept six to eight hours per night. 
• Sleep disturbances may accelerate neurodegeneration: In addition to contributing to beta-amyloid pathology, animal models of neurological diseases, such as Alzheimer's, suggest that chronic sleep insufficiency may accelerate the neurodegenerative process.

When taken as a whole, this research suggests that sleep and Alzheimer’s disease share a complex bidirectional relationship. While more research is needed to better understand this relationship, circadian rhythm and sleep-wake cycles may be ideal targets for potential interventions to slow the progression of Alzheimer’s disease and possibly even prevent its development.

Sleep Disturbance as a Modifiable Risk Factor for Alzheimer's Disease

In light of research surrounding circadian rhythm and Alzheimer's disease, the circadian rhythm has emerged as an interesting target for Alzheimer’s disease prevention. Therapy-based interventions, such as bright light therapy, can be utilized to regulate the circadian rhythm by gradually shifting sleeping patterns back to a “normal” sleep-wake pattern, thus reducing sleep-wake disturbances. This may aid in reducing the risk of developing Alzheimer’s disease in those with circadian dysfunction and may help slow the progression of the disease for those diagnosed with Alzheimer’s disease.

Aside from getting sufficient sleep, other Alzheimer's prevention strategies include:

• Quitting smoking.
• Exercising daily (30-60 minutes per day).
• Eating a heart-healthy diet.
• Minimizing stress.
• Controlling alcohol consumption.
• Increasing mental and social engagement.

The growing amount of research surrounding modifiable risk factors emphasizes the need to monitor the brain health of individuals with risk factors for Alzheimer's disease, including circadian rhythm and sleep-wake disorders. The brain health of all individuals who have known risk factors, whether modifiable or nonmodifiable, should be assessed and monitored early and frequently to detect neurocognitive changes as early as possible. Early detection of Alzheimer’s disease is crucial, as it can enable early intervention and, consequently, better health outcomes.