Alzheimer’s: Scientists find the cause of evening agitation

A new study has uncovered a biological clock circuit that may explain why people with Alzheimer’s disease or other forms of dementia can become more agitated or aggressive in the early evening.

Sundowning is a condition that is typically seen in people with Alzheimer’s, when behavior becomes restless, agitated, and aggressive, accompanied by confusion. Its name is derived from the fact that it usually begins or gets worse in the late afternoon or early evening.

Biological clocks are specific groups of proteins that communicate with cells in nearly every organ and most tissue in the body. They respond to changes in light and dark in the environment and give rise to the circadian rhythms – that is physical, behavioral, and mental changes that “follow a daily cycle.”

Scientists have discovered that the genes that make and control the various components of biological clocks are largely similar in humans, mice, fruit flies, fungi and many other organisms. While biological clocks are found nearly everywhere in the body, they are all synchronized by a “master clock’ in the brain.

In humans, mice, and other vertebrates, the master clock is located in the suprachiasmatic nucleus, which is a cluster of neurons inside the hypothalamus region of the brain. The cluster contains around 20,000 cells and receives signals directly from the eyes.

For their study, Prof. Saper and his colleagues measured the frequency and intensity of interactions between male mice as “resident mice” defended their territory against “intruder mice” that were introduced into their cages at different times of the day. “The mice,” explains Prof. Saper, “were more likely to be aggressive in the early evening around lights out, and least aggressive in the early morning, around lights on.” “It looks like aggressiveness,” he continues, “build up in mice during the lights on period, and reaches a peak around the end of the light period.”

In another set of experiments, the researchers manipulated the mice’s master biological clock by tweaking genes in the neurons that regulate it. They found that when they stopped the master clock neurons from being able to make a specific chemical messenger, or neurotransmitter, the mice lost their circadian pattern of aggression. Aggressiveness remained high all the time, showing no highs and lows.



They conclude that their results reveal a “functional” circuit through which “the suprachiasmatic nucleus [master] clock regulates aggression.” The patterns that they observed in the mice, says Prof. Saper, “mimic the patterns of increased aggression seen in patients during sundowning.” This would suggest that the circuit is damaged in some way in neurodegenerative diseases such as Alzheimer’s, he notes.

My Take:
As Prof. Saper goes on to say, “sundowning is often the reason that patients have to be institutionalized, and if clinicians can control this circuit to minimize aggressiveness at the end of the day, patients may be able to live at home longer.”

The neurotransmitter melatonin, produced in the pineal gland, as a response to stimulation from daylight, plays a vital role in this process. I highly advise against taking melatonin unless you are traveling and pass through a minimum of four times zones in 24 hours. Then a one-shot dose about an hour before you want to go to sleep can help reset the circadian rhythm.

Otherwise, Chaste Tree is a good alternative. Taken early in the morning upon arising it stimulates natural melatonin production during daylight hours. Darkness activates the melatonin and the ability to sleep ensues.

I believe that long term disruption of circadian rhythm is a factor in the development of Alzheimer’s. Good sleep patterns are one of the most important indicators of general health. Make sure your bedroom is dark, really dark, when you go the sleep. That means no led lights, TV, night lights or any other source of illumination.

Source: April 10, 2018 National Institutes of Health