Sleep disturbances exacerbate dysfunction in Alzheimer's

Chemical changes in brain cells caused by jet lag-like sleep disturbances may contribute to learning and memory loss in Alzheimer's, according to a study published in the Journal of Alzheimer's Disease.

Sleep disruption affects many older people and is especially linked with Alzheimer's.

Many older adults notice changes in their sleep, but these disturbances occur more frequently and tend to be more severe in Alzheimer's disease.

Sleep problems affecting people with Alzheimer's include inability to sleep and changes in the sleep schedule. The reason for this is not fully understood.

People with Alzheimer's may wake up more often and stay awake longer during the night. Brain wave studies show decreases in both dreaming and non-dreaming sleep stages.

Individuals may feel sleepy during the day but unable to sleep at night, and they may be restless or agitated in the late afternoon or early evening.

Experts estimate that people in the late stages of the disease spend about 40% of the night awake and a significant part of the daytime sleeping. Some experience a complete reversal of the usual day-night sleep pattern.

While sleep changes are more common later on in the disease, they have also been observed in the early stages.

Whether poor sleep accelerates Alzheimer's disease or vice versa is not clear, but the current findings suggest that it is the disruption of sleep that accelerates memory loss.

Disturbed sleep impairs performance in tasks

Researchers at the University of California-Irvine (UCI), have carried out research on mice that shows for the first time that circadian rhythm-altering sleep disruptions in the body's day-night cycle promote memory problems and chemical alterations in the brain.

The research tea, hopes that clinical application of this finding may lead to more emphasis on managing the sleep habits of people at risk for Alzheimer's disease and those with mild cognitive impairment.

To examine the link between learning, memory and circadian disturbances, the team altered normal light-dark patterns with an 8-hour shortening of the dark period every 3 days for young mice with Alzheimer's disease and normal mice.

The resulting jet lag greatly reduced activity in both sets of mice. In water maze tests, the Alzheimer's mouse models had significant learning impairments compared with the Alzheimer's mouse models that were not exposed to light-dark variations, and with normal jet-lagged mice.

In follow-up tissue studies, jet lag was found to cause a decrease in glutathione levels in the brain cells of all the mice. These levels were much lower in the Alzheimer's mouse models and corresponded to poor performance in the water maze tests.

Glutathione is a major antioxidant that helps prevent damage to essential cellular components. Glutathione deficiencies produce redox changes in brain cells. Redox reactions involve the transfer of electrons, which leads to alterations in the oxidation state of atoms and may affect brain metabolism and inflammation.

The researchers describes accelerated oxidative stress as a vital component in Alzheimer's-related learning and memory loss, noting that potential drug treatments could target these changes in redox reactions.

The researchers conclude:

"This study suggests that clinicians and caregivers should add good sleep habits to regular exercise and a healthy diet to maximize good memory."

Studies have found that sleep medications generally do not improve overall sleep quality for older adults, and some can cause serious side effects.

Some non-drug suggestions for helping people with Alzheimer's to sleep are:

• Regular times for eating and sleeping
• Daily exercise, but not within 4 hours of bedtime
• Ensuring the bedroom has a nightlight and a comfortable temperature
• Not staying in bed while awake; using the bed only for sleep.

References:

1.  UCI news release, accessed 29 October 2015.
2.  Additional source: Alzheimer’s Association, Treatments for sleep changes, accessed 29 October 2015.