COLUMBUS, Ohio – Valuable research provides the best evidence to date that the late-day anxiety and agitation sometimes seen in older institutionalized adults, especially those with dementia, has a biological basis in the brain.
The findings could help explain “sundowning,” a syndrome in which older adults show high levels of anxiety, agitation, general activity and delirium in late afternoon and evening, before they would normally go to bed.
What’s Going On in the Brain During Sundowning?
“It’s a big problem for caregivers. Patients can get aggressive and very disruptive,” said Tracy Bedrosian, lead author of the study and a doctoral student in neuroscience at Ohio State University.
“There have been a few clinical studies documenting sundowning, but until now there hasn’t been research in animals to see what’s going on in the brain to explain this.”
More Activity
The important study found that aged mice showed significantly more activity and more anxiety-like behaviors in the hours before they would normally sleep when compared to middle-aged mice – just like sundowning in humans.
In these aged mice, the researchers found changes in parts of their brain associated with attention, emotions, and arousal, all of which could be associated with the behavior seen in sundowning.
In addition, mice that were genetically engineered to have an Alzheimer’s-like disease also showed more anxiety before sleep than did other mice.
Biological Basis
“Some people have argued that sundowning could be explained just by a buildup of frustration of older people who couldn’t communicate their needs over the course of the day, or by other factors,” said Randy Nelson, co-author of the study and professor of neuroscience and psychology at Ohio State.
“But our findings suggest there is a real phenomenon going on here that has a biological basis.”
The study appears in the online Proceedings of the National Academy of Sciences.
In the first experiment, researchers compared middle-aged adult mice (7 months old) with aged mice (29 months old) that would resemble humans in their 80s.
Results showed that the aged mice were significantly more active than middle-aged mice in the two to three hours before they would normally go to sleep.
“The middle-aged mice had a distinct pattern of activity, with three peaks of activity during their waking hours,” Bedrosian said.
“But the aged mice had a flattened rhythm in which they showed the same level of activity throughout their active period.”
Evenings & Sundowning
That means that in the evening, when the middle aged mice would slow down compared to their peak activity levels, the aged mice kept going.
The mice were also tested for anxiety-like behaviors at two different times during their waking hours. The mice were placed in a maze where they were allowed to explore open areas – which are more anxiety-producing – or hide in enclosed areas.
The middle-aged mice showed consistent levels of anxiety at both times of the day. However, the aged mice showed more anxiety when tested soon before they would have gone to sleep, which is consistent with sundowning, Bedrosian said.
The Cholinergic System & Circadian Changes
There were also differences in the brains of the aged mice when compared to the middle aged mice. The researchers looked specifically at the cholinergic system, because loss of function in that system is associated with dementia and many of the circadian changes associated with ageing.
Findings in aged mice showed greater expression of a certain enzyme – acetylcholinesterase – before sleep than earlier in the day. High levels of this enzyme are associated with anxiety and agitation.
However, in the middle-aged mice, there were no time-of-day differences in the expression of this enzyme.
Nelson noted that drugs used to control levels of acetylcholinesterase are sometimes used on dementia patients, although there has been no research evidence that it actually had an effect on sundowning.
These drugs include:
| Brand Name | Generic Name |
| Aricept | donepezil |
| Exelon or Ebixa | rivastigmine |
| Reminyl or Razadyne | galantamine or galanthamine |
“These drugs were prescribed for other purposes, but it also seemed to calm patients down. Now we have some evidence on why it works,” Nelson said.
Anxiety, Agitation & Proteins
The researchers also found differences in expression of two other proteins in the brains of the aged mice that are also associated with behavioral disturbances.
“All of these results converge to suggest there are changes in the cholinergic systems of aged mice that may be contributing to the anxiety and agitation symptoms that we documented,” Bedrosian said.
In another experiment, the researchers used mice that were genetically engineered to develop Alzheimer’s-like disease in their brain. They were compared, at nine months of age, to similar wild-type mice of the same age.
The Alzheimer’s-like mice showed more anxiety-type behaviors when tested before they would normally sleep than they did when tested earlier in their waking period. That is consistent with sundowning in humans, the researchers said.
However, the wild-type mice showed no differences in anxiety levels based on the time of day they were tested.
Nelson said one of the theories about sundowning is that it is tied to disruptions that often occur in the biological clocks of older people, where their sleep-wake cycles are fragmented.
To test this theory, the researchers also treated the aged mice with melatonin for four weeks in order to help consolidate their circadian rhythms. However, this treatment did not work to reduce anxiety issues in the mice.
Nelson said melatonin alone may not work because it doesn’t deal with the disruptions in the cholinergic system that was identified in this study.
“We need to study whether treating cholinergic dysfunction alone or in combination with melatonin treatment will help deal with sundowning symptoms,” he said.
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I have no doubt that sundowning it is a chemical disorder and that can be controlled , in an empirical way, using natural supplements .
My aunt have advanced dementia and if she do not takes every day the following supplements ,she starts again with her "old"and odds behavior (as before we started to gives the supplements) ,with hallucinations ,delusions, agressiviness ,agitation , cyings, yells, etc , most the time of the day and most the time of the night .
We are using in an absolute empirical way ,and this is only an anedoctal report.
Only the doctor of the patient can gives permission and have to gives supervision in the use of the following supplements that are controlling not only sundowning , but her agressiviness,delusions ,agitation , hallucionations , insomnia , cryings , yells,etc.
In an empirical way we are giving:
1) L-CARNOSINE : 60 miligrams three times a day.( it is CARNOSINE and it is NOT L-carnitine).(only these small doses).
2) L-GLUCURONOLACTONE : 300 miligrams 2 to 4 times a day.
3) GLUCOSAMINE SULPHATE : 200 miligrams 3 to 4 times a day.
I know GLUCOSAMINE it is a supplement for joints.
But when she started to use GLUCOSAMINE for her joints we saw an amazing calmness and control of agressiviness and agitation.
We can find in the medical site PubMed SCIENTIFIC ARTICLES that shows that glucosamine stabilizes tau in the microtubules in the neurons, and works as an alternative fuel to the neurons too .
4) ACETYL L CARNITINE (ALCAR) – 30 to 50 miligrams three times a day.(it is NOT l-carnitine , but is ACETYL L-CARNITINE)( only these small doses).
5) EXTRA VIRGIN COCONUT OIL – One tea spoon three times a day.(if the patient have diarrhea even with these small doses , the caregivers makes massages with the oil in the thin skin of the arms with the tea spoon of the oil ,once the coconut oil has a comroved fast thras cutaneous absortion (according articles in PubMed)
A lot of friends of mine , after my report , are giving to their relatives with different types of dementia ,with the same amazing effects to enhances cognition,mood and to control the odd behaviors.
But this is only an anedoctal report , without none scientific foundation, based in empiric observation only.
Only the doctor of the patient can gives permissions,a nd knows the right sup´plements and the right doses to each supplement.
talk to the doctor of the patient.
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qi gong also helps tremendously . thank you for the supplement regime!
UPDATE : We are using in an absolute empirical way ,and under Physician prescription made in compounding pharmacies : 1) ACETYL L CARNITINE (ALCAR) – Starting with fifty miligrams three times a day and uptitrating to one hundred miligrams three to four times a day (it is NOT L-carnitine But is ACETYL L-CARNITINE- only these small doses).The last dose of the day is up 7:00 p.m. 2) L-CARNOSINE: Sixty miligrams to eighty miligrams three times a day.( it is CARNOSINE and it is NOT l-carnitine). But only these small doses. 3)ALPHA LIPOIC ACID – Twenty miligrams three times a day. 4)GLUCURONOLACTONE : 200 to 300 miligrams 2 to 5 times a day.THIS IS THE MAIN SUPPLEMENT. 5) EXTRA VIRGIN COCONUT OIL – One tea spoon three times a day.(if the patient have diarrhea even with these small doses , the caregivers do Not gives the oil by mouth ,but makes massages with the oil in the thin skin of the arms with the tea spoon of the oil ,once the coconut oil has a proved fast trans-cutaneous absortion(according articles in PubMed)
what about those that have had it since birth? you are not born with the dementia that everyone says it takes to have sundowners. so is it truly a chemical reaction from the wrong chemicals in the brain?
Carlos, are you also giving a dementia drug in combinations with these supplements? My mother us on Excelon but does experiebce Sundowning. You mention compounding…what combinations are being out together for the situation you deal with?
Dear C4AP:As my aunt has heart arrhythmias,the usual medicine drugs to dementias as the acetylcholynesterase inhibitors(rivastigmine,donepezil,etc.)gave side effects, worsening her heart arrhytmias,and she had fainting and dyarrheas too,etc.with such drugs,and she had to stops to takes it Ach inhibitors just in the first month of use,six years ago.And even with the NMDA antagonist memantine she had problems too. About delusions,agitation,hallucinations,etc.,her doctor tried different types of antipsycotics,in different times,and with very small doses to avoid more heart arrythmias,and some antipsychotics did not work to her,and others antipsychotics that worked in a mild way,gave to her important side effects as very low blood pressure,associated to dizziness and faintings,and worsened the heart arrhythmias.Then,at last,for her case,the supplements fits well.I described in the comments above the empirical use of it supplements.But this is an anedoctal report ,without none scientific foundation. Please, supplements only under physician prescription with small doses made in compounding pharmacies.Only the doctor of the patients knows what is the best to the patient.Never takes or gives none drug or supplements without physician prescription.
Continuing to C4AP :the nutraceuticals supplements in the safe and small doses, under physician prescription and supervision, maybe can be used as a supplementary or support therapy to the conventional drugs in dementias. But only under physician prescription with such minidoses made in compounding pharmacies. Talk to the doctor.
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Wow your article very informative. Thanks for sharing such a useful post.
I’m very close to having Dementia, yet :darkness &
Wintertime are harder for me
& it’s more depressive to me.
This type of weather prevents
you from being outside.