Chronic Stress Kills: High Cortisol Levels Damage the Brain, May Lead to Shorter Life and Neurodegenerative Diseases Such As Alzheimer’s and Parkinson’s

Researchers have noticed that there may be a connection between chronically elevated cortisol levels, typical of people under chronic stress, and damage to portions of the brain including the hippocampus and hypothalamus that are seen in neurodegenerative diseases of aging such as Alzheimer’s Disease and Parkinson’s Disease.

Poor Memory and Concentration Symptoms of High Cortisol and Alzheimer’s

One of the most prominent features of Alzheimer’s Disease is the inability to remember even simple personal facts such as the names and identities of relatives, locations of familiar places such as the neighborhood grocery store one has shopped at for decades, and recent personal activities.

People under high stress who have not been diagnosed with Alzheimer’s Disease also often experience symptoms such as memory loss, confusion, and impaired ability to focus and concentrate.

Such observations have led some scientists to wonder if there are underlying biological mechanisms that may explain these symptoms. High cortisol has been found to both impede the formation of new memories and to hinder the recall of previously formed memories. It’s also been found to damage regions of the brain important to memory and endocrine system functioning such as the hippocampus and hypothalamus.

(from Cortisol: Keeping a Dangerous Hormone in Check )

Researchers have found that cortisol can affect mood and behavior, and disrupt memory and recall.5 Administering cortisol to healthy volunteers has been shown to alter processes associated with prefrontal cortex functions, such as inhibitory control, attention regulation, and planning. Cortisol has significant interactions with the neurotransmitters, neuropeptides, and brain circuits that are associated with depressive symptoms. Because elevated cortisol levels also can affect the endocrine, metabolic, pro-inflammatory, and hemostatic factors that increase vulnerability to cardiovascular disease and other medical conditions, it is not surprising that depression is an independent risk factor for coronary artery disease. Even worse, recurring depressive symptoms result in cumulative injury to the hippocampus, which can further impair the feedback pathways for the hypothalamic-pituitary-adrenal axis and send already depressed individuals into even deeper depression.

Cortisol also plays a role in the progression of Alzheimer’s disease. The hippocampus is closely associated with the acquisition, retrieval, and consolidation of new memories. Excessive cortisol levels have neurotoxic effects on the hippocampus, resulting in atrophy and memory impairment.6 A study conducted at the University of Genova, Italy, found that cortisol levels are directly related to the degree of cognitive impairment in people with Alzheimer’s disease.7 These patients also had much lower levels of DHEA sulfate (DHEA-S), and therefore a dramatically higher cortisol:DHEA-S ratio than individuals without Alzheimer’s. This suggests that a reduction in cortisol levels could help treat people with Alzheimer’s, particularly when linked to DHEA supplementation.

DHEA is another hormone produced by the adrenal glands. Often when cortisol spikes high, DHEA levels fall. DHEA supplementation is often discussed as a means to help prevent damage from chronically elevated cortisol levels. As DHEA levels typically fall with age, it is also often discussed as an anti-aging strategy even in people with healthy cortisol levels and no sign of Alzheimer’s.


Commonly Used Blood Tests Often Result In Misdiagnosis of Cortisol Imbalances

Contrary to some widely held stereotypes reinforced by well-meaning titles like that of the article quoted above, cortisol itself is not truly dangerous by its mere presence. It’s not a toxin and in fact is necessary to the normal operation of the body. If you had no cortisol, you would be extremely sick with a condition such as Addison’s Disease which is often fatal if not treated. It requires cortisol replacement therapy for successful treatment, often by using physiological dosages of the drug hydrocortisone (bioidentical to cortisol) or supplements such as IsoCort that contains natural cortisol obtained from animals. What is dangerous is abnormal cortisol levels, either high or low.

High levels of cortisol are more commonly discussed as being a huge health problem for four main reasons.

First, when hydrocortisone was first introduced as a drug, doctors managed to severely hurt a lot of patients by overdosing them and damaging their immune systems, bones, causing elevated glucose and weight gain, and many other bad effects.

Second, high cortisol is the hallmark of the early stages of chronic stress that most people experience sometime in their lives. People who experience chronic stress for long times will initially have high cortisol levels. As the stress continues, many develop adrenal fatigue as body loses its ability to maintain proper levels of adrenal hormones, particularly cortisol and DHEA.

Third, there’s a condition known as Cushing’s Syndrome in which cortisol levels are extremely high throughout the day for various reasons such as tumors in the pituitary or adrenal glands and misuse of glucocorticoids drugs. Many common cortisol tests are set up to catch either this or the more rare condition Addison’s Disease in which there is virtually no cortisol left in the body.

Fourth, very few people completely lose the ability to make cortisol and many of the commonly used blood tests used to detect such conditions are unreliable at diagnosing people with low cortisol if they have any ability to make cortisol.

Very long periods of high stress in many people will eventually lead to a collapse of body’s ability to make adequate cortisol and cause very low levels with symptoms much like those of Addison’s Disease. That’s the case even though most such people still have the ability to make some cortisol and a single test at some times of the day can actually lead a doctor to believe they have healthy cortisol levels when that’s not the case. Such symptoms of chronically low or unstable cortisol are often found in diseases such as fibromyalgia and chronic fatigue syndrome that are believed to be largely triggered by extended durations of intense stress that overwhelm the body’s ability to heal itself.

It’s both ironic and confusing that high cortisol eventually leads to low cortisol and that both are devastating to health. You should walk away from reading this article with the idea that balanced cortisol levels are necessary and that any imbalance is likely to cause a confusing array of symptoms that are often misdiagnosed by doctors who should know better.

Healthy cortisol levels vary from high levels in the morning, helping you to get up and going, to low levels from bedtime to shortly before waking that allow you to sleep. Totally out-of-phase cortisol levels, such as very high levels during sleep time and very low levels during waking time, are among the most damaging and yet are often not detected by a single cortisol level test such as those doctors often use for screening for Addison’s and Cushing’s.

In my opinion, it’s not a coincidence that cortisol abnormalities are being found in many seemingly distinct diseases with extensive mental health symptoms including depression, anxiety, insomnia, fatigue, and cognitive impairments such as memory loss and confusion. If you or a loved one are suffering from such symptoms for longer than a few months, I’d strongly suggest examining the possibility that high, low, or otherwise unbalanced cortisol levels are in part contributing to the health problems. There’s more information about cortisol testing using four times per day (diurnal) saliva tests and some other simple inexpensive tests that often show signs of cortisol imbalances in my previous article Cortisol Imbalances May Cause Weight Gain, Depression, Anxiety, and Insomnia.

Computer Model of Cortisol-Aggravated Brain Damage

One of the earliest efforts at examining the possible connection between high cortisol and brain damage patterns similar to Alzheimer’s is a paper Twenty-four hour cortisol release profiles in patients with Alzheimer’s and Parkinson’s disease compared to normal controls: ultradian secretory pulsatility and diurnal variation that analyzes available data via computational biology models developed in the growing field of bioinformatics. The researchers worked to discern whether elevated cortisol is connected with brain damage similar to that found in Alzheimer’s and Parkinson’s patients. The researchers refer to their technique as an “in silico” study, meaning they have attempted to understand the problem via computer models. They found a correlation between acute (short-term) and chronic (long-term) cortisol elevations and damage to the brain’s hippocampus beyond that normally associated with aging without elevated cortisol levels. The damage from chronically high cortisol was significantly worse than from repeated acute spikes in cortisol. In their model, it appears that interventions that lower cortisol levels reduce damage to the hippocampus.

Aging induced a 12% decrease in hippocampus activity (HA), increased to 30% by acute and 40% by chronic elevations in cortisol. The biological intervention attenuated the cortisol associated decrease in HA by 2% in the acute cortisol simulation and by 8% in the chronic simulation.

Similarities Between Alzheimer’s and Adrenal Fatigue

It’s interesting to note that many of the identified risk factors for Alzheimer’s go hand-in-hand with other chronic stress related conditions such as adrenal fatigue. These includes diabetes, abnormal cortisol levels, mitochondrial dysfunction, oxidative damage, chronic inflammation, head trauma, and chronic viral or bacterial infections. All of these are often observed in people who suffer chronic stress and have symptoms that overlap with adrenal fatigue, chronic fatigue syndrome (commonly called myalgic encephalomyelitis outside of the US), and fibromyalgia. Most of these risks appear to be connected directly to the impact cortisol has on the body’s function. The chronic infection risk is probably related as a root cause in causing chronic stress that leads to adrenal problems.

While it might be temping to say that somebody with low cortisol levels would not be likely to suffer from these problems, it’s often the case that people with chronically low cortisol previously experienced chronically high cortisol for such a long time that their adrenal glands or organs that control them (the pituitary gland, hypothalamus, and hippocampus in particular) were damaged by the extended stress of producing so much cortisol and the effects it had on the rest of the body. Some people have conditions such as Addison’s Disease or Cushing’s Syndrome that can explain severely abnormal cortisol levels. But it’s likely that many, perhaps even most, people who have been chronically stressed for years and end up with unstable or low cortisol experienced chronic high cortisol before their adrenal glands eventually suffered enough damage from overuse that they no longer make sufficient cortisol. These people were therefore exposed to risk factors similar to those that are being tied to Alzheimer’s Disease.

Parkinson’s and Depression May Involve Brain Damage from High Cortisol

Cortisol abnormalities have also been found in many patients with Parkinson’s Disease. Many of the other risk factors and biological mechanisms involved in Parkinson’s are similar to those involved in Alzheimer’s Disease.

Similar comments can be made about “depression” which is overused as a diagnosis as if it is a root cause of disease in and of itself.

Dr. Daniel G. Amen is a neuroscientist and psychiatrist at the University of California at Irvine who is well-known as a controversial expert on the use of brain imaging studies used to assist in psychiatric diagnosis. He points out that diagnosing somebody with “depression” is like diagnosing a person with “chest pains” and failing to further investigate the root cause. He advocates for the use of SPECT (single photon emission computerized tomography) scans to help hone in on an accurate diagnosis when there are many conditions that could cause similar symptoms.

Depressive symptoms are common for a wide range of conditions with vastly different biological causes. Nearly everybody with adrenal dysfunction, Alzheimer’s, or Parkinson’s is also likely to have depressive symptoms. It would be highly unusual for such patients to not have such symptoms considering how debilitating these conditions can be. When doctors diagnose somebody with “depression” and prescribe antidepressants and find that they do not work, it is often because there is some condition causing the depressive symptoms that is not being adequately treated.

It’s not unusual for psychiatrists in particular to misdiagnose an illness. At present, the understanding of the brain is relatively weak compared to the understanding of many other organs. Furthermore, the interaction between the brain and the rest of the body is tremendously complicated. Getting adequate testing data to make a diagnosis is a further challenge for many conditions involving brain function. Testing for biochemical markers in the brain is often error-prone or expensive because of factors such as the blood-brain barrier getting in the way of being able to get useful measurements. Relatively inexpensive blood tests that are so helpful in many other areas of healthcare often won’t work for determining brain function. Unfortunately, that may mean invasive, painful, and more expensive test collections such as spinal taps must be used to collect cerebrospinal fluid used to get similar information that could have been easily obtained for other organs by a routine blood draw.

Someday scientists will develop a holistic model of the human body that will tie together all of these conditions with very similar symptoms based upon common elements of damage or impairment in certain areas of the brain and hormonal systems that affect the brain’s operation. They will also understand better just what tests are needed to differentiate between root causes of similar symptoms. For now, however, there are major gaps in understanding that often result in people getting a wrong diagnosis or not having any idea what treatments to try. Given this situation, anybody who has been suffering from the symptoms discussed in this article and does not think treatment is improving their condition should familiarize themselves with other possible causes besides whatever they have been diagnosed as having. It’s quite possible that such people have been wrongly diagnosed and will continue to suffer from inadequate treatment unless they take steps push their medical care providers into considering alternatives diagnoses and treatments.

Further Reading

Abnormal Cortisol Levels, Depression, Anxiety, and PTSD Are Signs of Long-Term Abuse and Psychological Trauma

Low Cortisol, Low CoQ10, and Mitochondrial Dysfunction Often Found in Adrenal Fatigue, Chronic Fatigue Syndrome, Fibromyalgia, and Myalgic Encephalomyelitis Patients

Tired All the Time for Months or Years? Here’s A Resource With Many Possible Explanations.

Cortisol Imbalances May Cause Weight Gain, Depression, Anxiety, and Insomnia

Depressed But Antidepressants Don’t Work? Adrenal Fatigue or Neurotransmitter Imbalances May Be Responsible.

Reducing Sedative and Addictive Side Effects of Anti-Anxiety Drugs Benzodiazepines (Xanax, Valium, etc.) with L-Theanine, Pregnenolone, and DHEA

Shilajit’s DBP Claimed to Enhance CoQ10 Function Inside Mitochondria

Vitamin-Like PQQ Offers Antioxidant, Neuroprotective, and Mitochondrial Health Benefits

L-Theanine for Anxiety, Insomnia, and Depression

Cortisol: Keeping a Dangerous Hormone in Check

Alzheimer’s Disease

Chronic Fatigue Syndrome

Fibromyalgia

Therapeutic Options for Fibromyalgia

Coenzyme Q10 levels reduced in chronic fatigue syndrome

Twenty-four hour cortisol release profiles in patients with Alzheimer’s and Parkinson’s disease compared to normal controls: ultradian secretory pulsatility and diurnal variation

The stress system in the human brain in depression and neurodegeneration

A blunted cortisol awakening response and hippocampal atrophy in type 2 diabetes mellitus

The key role of mitochondria in Alzheimer’s disease

Mitochondrial dysfunction is a trigger of Alzheimer’s disease pathophysiology

Chronic stress attenuates glucocorticoid negative feedback: involvement of the prefrontal cortex and hippocampus


These statements have not been evaluated by the Food and Drug Administration. The products mentioned in this post and on this website are not intended to diagnose, treat, cure or prevent any disease. The information presented here is for educational purposes and does not constitute medical advice. Please obtain medical advice from qualified healthcare providers.


Comments

Chronic Stress Kills: High Cortisol Levels Damage the Brain, May Lead to Shorter Life and Neurodegenerative Diseases Such As Alzheimer’s and Parkinson’s — 8 Comments

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  5. My cousin has extremely excessive high levels of cortisone. Over 1000 mg. She has been to various doctors for 10 years and no one has been able to help her. She had 30 minutes sleep last night. In one week, over 110 hours she had one hours sleep! She may not sleep AT ALL for 2 nights then have 3 hours on the third night. Sleeping tablets and drugs don’t work. She is 50, works has 2 grown children. She is extremely skinny – not obese like most articles state high cortisol can cause. She is a bit OCD with house cleaning and gets very irritated if not completely clean all the time.

    Does anyone know how to treat this severe insomnia????

    Therese

    • Therese,

      Can you recheck the test measurement and particularly the units? Are you sure they were mg (milligrams) and not mcg (micrograms)?

      What kind of test was it — blood, saliva, or urine? When was it run? Usually morning tests show higher results that afternoon or night tests as the release of cortisol peaks around waking times. Urine tests are usually run for 24 hours so they don’t see the variations during the day.

      Usually the units are ng/ml for saliva tests for cortisol. The upper limit of the reference range for many of those tests is around 10 ng/ml of cortisol.

      Blood tests use a different range and are usually measured in nmol/L or micrograms/dL.

      Between blood and saliva tests, the saliva tests run four times in one day (first test shortly after waking, last one right before doing to bed) is generally more helpful because you can see the daily variation in cortisol levels from that.

      Urine tests may just use a single mass measurement for cortisol accumulated over the test period which is usually 24 hours. Often the urine test is interpreted such that more than 100 micrograms of cortisol in the urine over 24 hours indicates a problem.

      Since you mentioned milligrams (1000 mg!) that hints that maybe the test was a urine test so in that case the cortisol levels would be over 10,000 times normal if the measurement and units you reported were correct. With test results like that, it is no wonder she has severe sleep problems. She probably has very high cortisol levels all day long, but without a four times saliva test series to be sure you can’t rule out some unlikely oddity such as her cortisol release peaks at night and is lower than normal during the day.

      Has she been diagnosed with Cushing’s disease or syndrome? This is very rare, some statistics are about 10 in 1 million people. Probably none of her doctors would have ever seen it unless she’s been to see an endocrinologist. Even they might be confused, however, as the classic symptoms of Cushing’s include high weight. But in theory, really high cortisol levels could cause the body to break down muscle tissue in a catabolic process and/or focus the body’s energy usage on areas other than the gastrointestinal system needed to absorb nutrients. One or both of these could be why she is thin despite the high cortisol.

      Has she also had an ACTH test? This tests for stimulating hormones that the pituitary gland makes to control operation of adrenal glands.

      High CRH (corticotropin release hormone) from the brain’s hypothalamus could drive the pituitary to overproduce ACTH which would probably make the adrenals produce way too much cortisol.

      Has she ever had MRI images taken of her pituitary and adrenal glands or her brain and particular the hypothalamus? These are safer than CT scans (since CT uses X-rays and MRI does not) and are often used to find problems such as tumors or other unusual growth or damage in internal organs.

      I don’t want to be alarmist, but sometimes extremely high levels of hormones can be caused by a tumor (sometimes a cancerous one) in a gland. In this case it could be the adrenals or maybe the pituitary gland or even a brain tumor in the hypothalamus region as any of those could influence how the adrenal glands produce cortisol. There are reports that some lung cancers can also produce excess ACTH that could drive the adrenals to overproduce cortisol.

      Does she smoke? Smoking could produce both weight loss and trigger a lung cancer that could produce excess ACTH that could drive the adrenals into making massive amounts of cortisol as you are describing.

      Has she had other hormones tested, in particular pregnenolone, progesterone, DHEA, testosterone, and estradiol? Something wrong in the body could be causing too much pregnenolone and progesterone to be converted to cortisol. This might show up as low levels of one or both hormones. Or maybe the body is way overproducing one of both of pregnenolone or progesterone and that could lead to excess cortisol production.

      If you can answer back on some of the questions above, maybe that would help me to suggest more things to check.

      Lowering such high cortisol levels with supplements may not be easy to do effectively. If there’s a tumor behind the problem, surgical removal of the tumor is more likely to be helpful. But she is going to need more tests to figure that one out.

      First things first, look to eliminate anything that is likely to drive cortisol higher. For instance, if she loves licorice then make sure it is all DGL licorice because full spectrum licorice will counter the enzyme that degrades cortisol and thus may raise cortisol levels. This is why licorice root extract (full spectrum, not DGL) is often suggested to help people with lower than normal cortisol levels.

      Caffeine is reported by some to raise cortisol levels, maybe on the order of 30% to 50% increases from a cup of coffee. If she consumes a lot of caffeine, not surprising if she gets so little sleep, that could be part of the problem. Cutting caffeine cold is often not a good idea, however, and is likely to produce headaches. Maybe try to gradually lower it?

      Are there any medications she is taking? A few could raise cortisol.

      Some adaptogens are reputed to help normalize cortisol levels, either raising low cortisol or lowering high cortisol. Ashwagandha comes to mind, the Sensoril brand of standardized ingredient is probably the best studied and is available from many vendors and is relatively inexpensive. Rhodiola rosea is also reputed to help normalize cortisol levels.

      Phosphatidylserine (PS) is reputed to lower cortisol levels, it’s probably worth a try since it helps repair damage to brain cell membranes and over time high cortisol damages the brain. Unfortunately it is not cheap.

      As for the sleep problems, what medications has she tried? What were the effects and side effects? I would guess that Trazodone, Ambien, Lunesta, and meds like that might have been tried but would not have worked very well because of the very high cortisol levels overcoming their effects unless their dosages are raised so high that she will be sort of a “brain-dead zombie” when she is awake.

      For mild to moderate sleep problems such as people get from anxiety, I’d normally recommend supplements such as melatonin, L-theanine, and tryptophan. However, melatonin may interact with cortisol although it generally is supposed to be an inverse relationship — i.e., daily high levels of melatonin at bedtime or in the early sleeping period are supposed to correspond to daily low levels of cortisol. There are some reports that melatonin could increase cortisol levels. I would not discount that melatonin could be helpful, but would simply be cautious about trying it out. I don’t see any reason why L-theanine and tryptophan supplements would be a problem to try from what you have written so far. Both are likely to improve sleep and mood in many people with mild anxiety and poor sleep and depressed mood. But the cortisol levels being so high (if I am understanding your “1000mg” number which as I said seems like the units are wrong) could get in the way.

      Pregnenolone and DHEA supplements can help deal with stress, too, but I would avoid using them until she has tests that show was is going on with those hormones as it is at least possible they could be also very messed up along with the cortisol. Generally speaking, I think both pregnenolone and DHEA would be highly recommended in many people with low cortisol levels but it is really much safer to get hormone tests to know what is going on before adding more of any hormone.

      Alison

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