- Sundowning in Alzheimer’s disease patients is a symptom that occurs in the late afternoon and evening.
- It is characterized by increased confusion, agitation, anxiety, and mood swings.
- The causes are little understood, and it has been assumed to be due to the effect of Alzheimer’s disease on the brain.
- Recent research in mouse models of Alzheimer’s disease showed increased light sensitivity due to changes in the retina.
Sundowning is a debilitating symptom of Alzheimer’s disease that causes individuals to experience worsening dementia symptoms in the late afternoon and evening.
Some researchers have assumed this symptom was due to changes in the brain, and indeed, recently a study showed that circadian disruptions in the immune cells in the brains of Alzheimer’s patients could worsen the buildup of amyloid beta in the brain.
The buildup of this protein is one of the defining characteristics of Alzheimer’s disease.
Dr. Alexander Lapa, a psychiatrist from the Rehab Clinics Group told Medical News Today in an email:
“Sundowning can be distressing for both the affected individual and their caregivers. The increase in confusion and agitation can lead to increased care needs and may cause significant disruption to daily routines. In some cases, sundowning may even compromise the safety of the patient or others around them.”
He added that many physicians suggest patients with Alzheimer’s disease stick to a daily routine with consistent timings, calming activities, minimizing noise, and ensuring adequate lighting in the evening.
Increased light sensitivity in mouse models of Alzheimer’s
Despite the debilitating nature of this symptom of Alzheimer’s disease, the cause of sundowning is not known. The fact that it occurs in the mid- and later stages of Alzheimer’s disease means that it may occur alongside a number of other symptoms, such as disturbed sleep or forgetting to eat and drink, or side effects of certain drugs, all of which have been linked to sundowning.
As sleep disturbance has been strongly associated with Alzheimer’s disease in the past, a team of researchers from the University of Virginia, Charlottesville, VA, decided to investigate this link more thoroughly. Their findings recently appeared in Frontiers to Aging Neuroscience.
It had been assumed that disruption to the brain caused by the accumulation of amyloid beta protein, and tau protein, both hallmarks of Alzheimer’s disease, could also cause sleep disturbance.
“We were interested in why sleep and circadian rhythms are disrupted in Alzheimer’s disease,” lead author Dr. Heather Ferris, assistant professor of medicine at the University of Virginia, told MNT.
“We actually thought the brain would be where the problem was occurring, but after ruling out several causes in the brain we turned our attention to the retina,“ she said.
“The retina has specialized cells called intrinsically photosensitive retinal ganglion cells,“ Dr. Ferris explained. “These are light-sensitive cells, but they are not used for vision. Rather, these cells are used to tell the brain that it is daytime.“
“We found that in [Alzheimer’s disease model] mice we could trigger these cells with much less light and that there were more of these cells in the retina,” she told MNT.
Searching for the cause of sundowning
To discover this, researchers first used mouse models with genetic mutations that mimicked Alzheimer’s disease, as well as controls. First, they exposed 13-month-old female mice to a 6-hour shift in their exposure to daylight, before returning to a normal 24-hour routine, to mimic jet lag.
They found that the mouse models of Alzheimer’s disease retrained to a 24-hour clock routine quicker than controls.
Researchers first hypothesized that this difference was due to a higher level of microglia, a type of brain-based immune cell that is found around amyloid beta plaques, as it attempts to clear them.
However, reducing the number of microglia in the mouse models of Alzheimer’s disease did not affect their quicker return to a normal 24-hour clock after jet lag.
Next, researchers showed that the mouse models of Alzhiemer’s disease were more likely to respond behaviourally to changes in lighting than wild-type mice, suggesting they were more sensitive to light reception.
This finding led the researchers to conclude that Alzheimer’s disease was affecting the retina, rather than the brain.
“The photosensitive cells that regulate circadian rhythms are located in the retina. They travel through the optic nerve to communicate with the brain, but the light-sensitive protein they make, called melanopsin, is in the retina and it was an increase in melanopsin that we observed in the [Alzheimer’s disease] mice,” Dr. Ferris explained.
How to potentially treat sundowning
Previous research backs up this idea: Amyloid and tau proteins are detectable in the retina in Alzheimer’s disease patients, and the breakdown of the retinal blood barrier in Alzheimer’s patients has also been observed.
The finding that the retina may be affected in a way that increases light sensitivity in a mouse model of Alzheimer’s disease could suggest new ways to approach dealing with sundowning.
Dr. Ferris said she was hoping to test this theory in the future. “Currently physicians recommend keeping people with Alzheimer’s disease on a strict light/sleep and eating schedule to try and keep them in normal rhythms as much as possible,“ she noted.
According to her, light therapy might be the answer:
“Our research suggests that lower levels of light than might be expected could thwart these efforts. We next hope to test if we can prevent some of the changes in behavior by reducing the light exposure at certain times or changing the wavelength of light in order to make such therapies more successful.”
“Right now, beyond keeping a regular schedule, it makes sense to try to reduce exposure to blue light (screens) in the evening as this type of light is most likely to trigger melanopsin and disrupt sleep and circadian rhythms — whether you have Alzheimer’s disease or not,” she added.
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