RSS Feed Print
Cortisol and sundowning - thoughts?
AlphaLeah
Posted: Monday, January 9, 2012 9:00 AM
I have fibromyalgia and adrenal insufficiency and I experience something that sounds very much like what people describe as sundowning.

In adrenal insufficiency, your levels of cortisol are too low. Ideally, our levels of cortisol are highest in the morning and slowly lessen throughout the day, so that there is minimal cortisol in our blood when it's time for us to sleep. Cortisol is the "stress" or "fight or flight" hormone. Normal range for serum cortisol is something like 4-150 in bloodwork from blood taken first thing in the morning. When mine was tested by my current doctor/goddess, it was found to be 5. So that's the highest it is all day. 

Which means my serum cortisol is at a point first thing in the morning that it should be right before bed. The result is that I can't think clearly, and that cognitive distress increases as the day goes on. It reaches its worst around 5pm when I - literally - cannot think. I get completely overwhelmed if more than one person is talking to me, very easily overstimulated, feel panicky, depressed, irritable and the urge to flee. Often, now that we know what is going on, I just go upstairs and lie down for a bit.

Now - because of my current doctor/goddess - I have begun taking bio-identical cortisol. We are starting at a very low dose, but already the impact is amazing in terms of my ability to think complex thoughts again. And I'm not having any of the side effects associated with artificial hydrocortisol like predinsone and other such medications. So I think we're on the right track and am excited about the future.

All of this information to brings me to my question: have their been any studies of the cortisol levels in people with dementia?
onward
Posted: Monday, January 9, 2012 9:57 AM
Joined: 12/20/2011
Posts: 217


That's really interesting.  Thanks for posting.

 

Google scholar is a good search engine:
http://scholar.google.com/ 

 

I don't have time to do much searching right now but here's something I noticed.  

 

Associations of Serum Cortisol with Cognitive Function and Dementia: The Rotterdam Study 

 

2011

 

Higher levels of cortisol have been observed in persons with cognitive decline and dementia. It is unknown whether these higher levels are a cause or a consequence of disease. We investigated whether morning levels of serum cortisol were associated with cognitive function, cognitive decline, and the risk of dementia and Alzheimer's disease in the Rotterdam Study, a large prospective population based cohort study. Cortisol levels were assessed in fasting blood serum in 3341 participants, who were free of dementia at baseline (1997–1999). Cognitive function was assessed with a dedicated neuropsychological test battery at baseline and at follow-up examination (2002–2004). In addition, the cohort was continuously monitored for incident dementia until January 1, 2007. After a mean follow-up of 7.1 years, 243 participants had developed dementia, of whom 210 were diagnosed with Alzheimer's disease. Morning serum levels of cortisol were neither related to cognitive function at baseline, nor to annual cognitive decline. There was no relation between serum levels of cortisol and the risk of developing dementia or Alzheimer's disease. These results suggest that that morning serum cortisol is not a causal factor in the development of dementia.

 

http://iospress.metapress.com/content/r71qu4j5n629u241/ 

 

 

_________________

 

Thanks again for posting.  Maybe others will find more info to post, more closely related to sundowning.

 

 


Lane Simonian
Posted: Monday, January 9, 2012 10:14 AM
Joined: 12/12/2011
Posts: 4845


High levels of cortisol may increase the risk of Alzheimer's disease by increasing the release of glucose.  Cortisol levels are higher in some patients with early Alzheimer's disease. http://www.ncbi.nlm.nih.gov/pubmed/17716786 It is possible that later in the disease the release of more glucose is helpful as glucose transport systems are compromised in patients with Alzheimer's disease resulting in a lack of glucose in different regions of the brain. http://www.ncbi.nlm.nih.gov/pubmed/8667045 

 

The causes of sundowning are not well-known.  Low levels of melatonin, high levels of certain hormones, and low levels of glucose may all play a role.  The following article does not explain sundowning, but does provide interesting information on the possible relationship between epinephrine (adrenaline) and behavior in Alzheimer's patients.http://www.nature.com/npp/journal/v19/n6/full/1395237a.html 


Lane Simonian
Posted: Monday, January 9, 2012 10:42 AM
Joined: 12/12/2011
Posts: 4845


I did not have a chance to read Onward's reply before I posted my own.  There may not be a connection between high cortisol levels and Alzheimer's disease (perhaps the levels of glucose released due to high levels of cortisol are not enough to trigger Alzheimer's disease by themselves).  It could be that stress (which can cause high levels of cortisol) or depression (which may in some case be related to high levels of cortisol) are the primary culprits.  Of course, as you know, low levels of cortisol also create problems.  For people with low levels of cortisol to begin with, taking cortisol would not be an issue.  It may or may not be an issue for others. It is not clear yet whether or not it would help with sundowning.
onward
Posted: Monday, January 9, 2012 12:41 PM
Joined: 12/20/2011
Posts: 217


 AlphaLeah, here's another cortisol study I came across, more specifically related to sundowning:

 

Diurnal Variation of Cortisol in People With Dementia: Relationship to Cognition and Illness Burden

January 27, 2011

Cortisol patterns in nursing home residents with dementia are described and examined in relation to cognition and comorbid illnesses. Saliva was sampled 4 times in a 24-hour period (week 1) and at the same times 1 week later (week 2). In general, cortisol levels decreased from morning to evening, with 50% exhibiting a negative slope. In contrast, 38% of the participants had a relatively flat cortisol diurnal rhythm, and 7% exhibited an afternoon increase. The cortisol pattern was consistent between weeks 1 and 2 for 39% with a negative slope, 13% with a flat profile, and for 2% with an afternoon increase pattern. Cortisol rhythm was not statistically significantly related to cognition or illness burden. While this study contributes to the understanding of differences in the diurnal pattern of cortisol for older adults with dementia, more research is needed to understand the etiology of the differences and the biological mechanisms involved.


Billstrailrunning
Posted: Monday, January 9, 2012 1:12 PM
Joined: 12/15/2011
Posts: 6


 Cortisol does play a strong role in sundowning.  More specifically, delusions, irritability, aggressiveness, etc. are all cortisol driven.  With AD, there is as we all know progressive loss of neuronal tissue within the brain and as a compensatory response there is an increase of cortisol receptors on surviving brain cells.  The increase in cortisol receptors leads to a higher density of cortisol receptors than would be normal and this means that the brain becomes hypersensitized to cortisol presence, in turn leading to the abnormal behaviors associated with sundowning.

Prazosin has its therapeutic impact by acting as a nor-adrenergic blocker, and it is this effect that is associated with reduction of sundown symptoms in AD patients fortunate enough to have access to prazosin.  In other words prazosin by blocking cortisol impact on surviving brain cells (think taking shelter from the rain using an umbrella), attenuates the sundowning symptoms.  Again, it is not the absolute amount of cortisol but rather the AD brains altered sensitivity to it that leads to the sundowning symptoms.  In addition to prazosin, sleep in sufficient quantity and quality also mitigates the impact of cortisol on the AD brain.  Prazosin also has benefit  for sleep quality by means of increasing REM sleep time for AD patients which seems to have a favorable impact on normalizing the AD brain response to cortisol.  Excessive brain response to otherwise normal levels of cortisol in the brain also has an inflammatory effect on surviving brain tissue that probably hastens the demise of more brain cells, leading to even higher density of cortisol receptors on remaining brain cells, resulting in a positive feedback loop of sorts that characterizes the cascading progression of AD and corresponding worsening of sundowning behaviors.  Prazosin does appear to have the ability to slow that progression and also improve the quality of life of the AD patient and their caregivers. Mirtazapine (Remeron) administered at bedtime, may potentate prazosin beneficial effects on down-regulation of cortisol by further improving quality and quantity of sleep both at night and also during afternoon napping.
Bottomline:  prazosin will not halt AD progression but I am convinced through my personal observations of its effect on my AD wife that prazosin has a very beneficial impact on sundowning and related behaviors in AD patients and probably does slow AD progression as described above.  Prazosin when used in concert with mirtazapine and very good sleep hygiene can lead to further slowing of AD progression and at the same time mitigate many of the stressful symptoms of AD.
Bill


Lane Simonian
Posted: Monday, January 9, 2012 2:36 PM
Joined: 12/12/2011
Posts: 4845


This three part series does not resolve the issue of whether cortisol is a risk factor for Alzheimer's disease, a symptom of Alzheimer's disease, or both but it does provide some interesting information http://www.dementiatoday.com/2011/12/21/stress-and-ad-does-one-beget-the-other/ 

I was quite interested in the information presented by Bill about the negative relationship between cortisol and sundowning.  It wouldn't have necessarily showed causation, but it would have been intersting to know in the study cited by Onward if the patients who showed an increase in cortisol as the day progressed were the ones who experienced sundowning. 


onward
Posted: Monday, January 9, 2012 3:15 PM
Joined: 12/20/2011
Posts: 217


Billstrailrunning wrote:

 Cortisol does play a strong role in sundowning.  More specifically, delusions, irritability, aggressiveness, etc. are all cortisol driven.  With AD, there is as we all know progressive loss of neuronal tissue within the brain and as a compensatory response there is an increase of cortisol receptors on surviving brain cells...

Again, it is not the absolute amount of cortisol but rather the AD brains altered sensitivity to it that leads to the sundowning symptoms...

 


Bill, thanks.  It's good to see you posting here.


Lane Simonian
Posted: Monday, January 9, 2012 10:32 PM
Joined: 12/12/2011
Posts: 4845


Catechol-O-methyltransferase inhbition may explain behavioral issues in some Alzheimer's patients. Catechol-O-methyltransferase increases both b-adrenergic and a-adrenergic activityhttp://www.jneurosci.org/content/17/14/5573.short 

http://www.ncbi.nlm.nih.gov/pubmed/17084978 

https://docs.google.com/viewer?a=v&q=cache:q6dK1S_jFr4J:www.ncbi.nlm.nih.gov/pmc/articles/PMC2018297/pdf/amjpathol00736-0061.pdf+catechol-o-methyltransferase+inhibitor+adrenergic+receptors&hl=en&gl=us&pid=bl&srcid=ADGEESjXoxH4K4ys9ipIt57WaZtHOPHZsCvLR3fPWfXFtvQ-Qpv4ft8VpYQ3iynjfzrMH5qekeW-f6FIOTB8GJ-PG6OlpUrMV9RHoBWPDlx-8aVAAiO8ORp20CzyOxrSb6rpks7eBMBq&sig=AHIEtbQeIp2fSgWpeJwbJpKtnSLGWw4EGQ 

So cortisol would increase the incidences of sundowning.  Thanks again to Bill for educating me (and probably others) on this aspect of Alzheimer's disease.


JAB
Posted: Tuesday, January 10, 2012 1:43 PM
Joined: 11/30/2011
Posts: 740


BILL!!!  It's about time you showed up!  Where you been?

 

"Sundowning" is a misnomer.  Some studies have concluded that more "sundowning" takes place in the early morning than in the evening.  Others have concluded there is no such thing.  It's an interesting, if confusing, area of research.  See:


http://www.alzcompend.info/?p=268 


Billstrailrunning
Posted: Tuesday, January 10, 2012 2:40 PM
Joined: 12/15/2011
Posts: 6


 JAB,

I've been busy, busy, busy at the J.O.B.  Still am for that matter.
Yes I agree the term "sundowning" is a misnomer.  That said its occurrence is clearly tied to sleep.  Because most researchers are not looking at sleep or the lack thereof it is often overlooked.
Yes, my wife "sundowns" at rise time, but not always.  If she sleeps bad that night she sundowns at rise time.  If she has little or no REM time the night before, she sundowns. She may even sleep very well and sundown at rise time.  Why?  Probable sleep inertia... The groggy feeling many sometimes have on awakening.  
Most of her sundowning does occur around 5 pm, but almost always can be avoided by a prior nap, or pre-dosing with prazosin, or a really great night of sleep the night before.
I can tell by just looking at her what is coming...she looks tired around the eyes. When I see that I either get her head down for a brief nap of give her 1-3 mg prazosin.
She often sundowns at bedtime and always before I give her her bedtime prazosin. If I get it in her before she starts looking sleepy or becomes delusional (e.g., I'm going home now.  This is not my house. I don't live here.  I'm going home to mothers...that is where I live), then sundowning does not occur. If I totally miss the window of opportunity then I get the prazosin in her (only very rarely has she refused to take her prazosin despite her vitriolic behavior), encourage her to lie down and rest, and then come back 5-10 minutes later to help her get into her PJs and tuck her in bed.  At that time she is somewhat weepy, very contrite and trying to reassure me she did not want to be mean or hateful to me. So, that is how we experience sundowning at our home. Interestingly she has total recall as to how she behaved and can only tell me she had no control over her behavior even as she was appalled at her own actions as she was in the midst of her episode.
Bottom line:  anything that helps the patient get more and better quality sleep should help sundowning.  Most, if not all AD patients sleep terrible so daytime tiredness, sleepiness, and fatigue is no surprise and with no tolerance to even the slightest stress they become irritable, angry, frustrated, and aggressive.  But you know, with sufficient chronic sleep loss, so does everyone.  Go Figure!
Pass the prazosin please!
Bill