Is Brain Fog Real?
| Is Brain Fog Real?|
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Is Brain Fog Real?
We've been told that brain fog is really just post-surgical recovery, "normal" aging, lack of sleep from hot flashes, the stress of many midlife roles, other physical problems like hypothyroid, or situational depression. But HRT seemed to clear up my brain fog, so I wanted to find out whether it was my imagination.
On the contrary, it turns out that there are researchers who think that brain function might be the major reason to take estrogen replacement. (4)
So it might all be in your head, but it's not in your imagination!
PARTS OF THE BRAIN
There's a huge three-way intersection in the brain and a really complicated traffic pattern of hormones coming in from all the glands, chemicals in the brain that spread signals, and communication with the rest of the body.
The oldest part of the brain--the reptile brain--controls the basics: hunger, temperature, aggression, fight or flight. This is the part in charge of hot flashes and a lot of the mystery of the hormone jungle.
Wrapped around the reptile brain is the early mammal brain (or "rat brain"). It controls feelings, mood, memory, and reproduction. And wrapped all around the whole thing is the cortex--the primate brain (I'll call it "chimp" because after all the human brain contains all three parts). Human beings are of course the primate with the biggest, flashiest cortex, which does all the heavy lifting with words and math and analyzing problems.(5)
So, when we're dealing with hormones, we're dealing with the intersection between the reptile, the rat, and the chimp brains. In the intersection sits a group of traffic cops--the hippocampus (the memory center), the amygdala (the fear center, not the Princess in The Phantom Menace), and the hypothalamus (the chief of police or master gland).
The hypothalamus sits right on top of the pituitary gland, which takes orders from the hypothalamus and sends them out to other glands like the thyroid, the adrenals, and the ovaries (or testes). The pituitary is the source of all the stimulating hormones that our doctors are always measuring. (5, 44)
Leading into and out of this intersection are neurons--the 12 billion to 100 billion cells of the central nervous system (spine and brain). They all have a cell body, long threads that reach out like fingers (dendrites) toward the cells around them, and long threads that wave a button around (axons), almost reaching but not quite touching the neighboring cells' fingers.
Electrochemical pulses jump the gap between one cell's axon and another cell's dendrite and send messages that way from cell to cell. It's like little spark plugs running the body, sparking and setting off reactions so the engine goes. And the traffic cops are controlling how all the cells are firing. They can make it easier or harder for the spark to go. And some of them really go--sending as many as 1,000 sparks each second.
For messages to jump the gap they need "neurotransmitters"--or chemicals that send (transmit) a pulse from one neuron to another. The neurotransmitters act like little keys, turning the engine ignition of the cells on and off or shifting them into idle or high gear. (5)
As it turns out, estrogen hangs out with the traffic cops and the chief of police a lot--or to put it another way, the limbic system of amygdala, hippocampus, and hypothalamus have a very large number of estrogen receptors that affect everything about us. In fact, songbirds, which need estrogen in the hippocampus to sing, can actually make estrogen in the hippocampus, just to make sure they get enough.(20)
Better Blood Circulation
Estrogen helps the brain in many ways. One way is with basic circulation. It opens blood vessels up, relaxing them. It reduces blood platelet clumping that can block an artery in the brain. It balances cholesterol so that there's less arteriosclerosis in the brain to clog the blood flow. (11, 17) Even more specific, estrogen increases the flow of blood to the hippocampus (seat of memory), bringing with it oxygen and glucose, which the brain needs by the bucket.(4, 7) And estrogen decreases inflammation in the blood vessels and acts like an anti-oxidant, preventing damage. (4, 11)
More Connections between Brain Cells
Estrogen actually increases the number of synapses, causing new dendrites and axons to reach out toward each other from cell to cell. The more synapses there are, the better the brain works, the more connections it can make. When estrogen levels drop in mice after their ovaries are removed, there are fewer and fewer synapses so there's less traffic, fewer messages, and less going on in the brain.(9) The decline is fast and significant when estrogen is low. (23) When estrogen is added, however, axons and dendrites grow back. This is because they have estrogen receptors. (30)
More Brain Cells
Even better than synapses, estrogen actually causes new neurons to grow. This is startling. Scientists used to think that the number of brain cells was fixed in childhood, and all you could do is slow down the loss of brain cells, but no. (4) In rats, they've shown that the number of neurons actually shifts with the hormone cycle. At the highest levels of estrogen, the rats have 50% more new cells. (7) And a lot of those neurons develop in the hypothalamus and hippocampus.(17)
Cells that Live Longer
Another wonderful thing that they're finding is that estrogen actually slows down the aging process, cell by cell, in the brain, so the cells don't die as early. This process is called "apoptosis"--the natural preprogrammed death of the cell. Estrogen slows it down. The more cells, the more connections and the better the brain works. (7, 18)
Altogether, this adds up to brains that stay younger longer. When they've done imaging of women doing mental tasks, they found that older women taking estrogen had brains that behaved like the brains of young women.(40)
Women know something is going on when estrogen drops: 62% of women at midlife report some type of undesirable memory change, most often difficulty recalling words or numbers, forgetting why one has just walked into a room, and just generally being less able to pay attention. (26)
When you look at what girls do better than boys and what transsexuals experience when switching to high levels of estrogen, certain things about estrogen seem to be true. Estrogen should help with proper name recall (that inability to fill in the blank), remembering word pairs (19), recalling the content of paragraphs, (20) reading visual face cues (20), and figural memory. (20)
But when they give controlled memory tests to women on HRT, they get inconsistent results. Some have decided that any effect from estrogen is from better blood circulation and more neurons and synapses. Estrogen just increases the general speed of processing (22) or is a general effect from fewer hot flashes and better sleep.(17)
But this wouldn't explain why the traffic cops at the center of memory have a lot of estrogen receptors. It also wouldn't explain why a 1998 study at Johns Hopkins that used PET brain scans of estrogen users and nonusers doing memory tasks showed that different parts of the brain lit up for estrogen users while doing verbal and visual memory than for the nonusers.(8) It's not a general all over effect. Estrogen is doing something specific.
Many of the tests they use for memory are quite simple and only require you to parrot back information that they just handed to you. The nonusers do as well as users of estrogen on these short-term, simple memory tests. It's possible that the tests are just so easy that everyone does well.
But they noticed something about rats, who after all have the part of the brain that we're talking about here--emotions and memories. The rats without ovaries that were taking estrogen weren't that much better than the rats without ovaries without HRT on the regular old mazes where all you had to do was learn the route through the maze and then repeat it.
But the harder the researchers make the task, the better the estrogen rats do compared to the rats without estrogen. When they put the rats into really complicated mazes, called radial arm mazes, where the rats have to take the memory and think through the problem of predicting where the half peanuts should be, the rats with estrogen did far far better. When they made the rats wait several hours right in the middle of the task and then put them back in it, causing them to remember where they were in thinking through the problem, the estrogen rats did even better than the no estrogen rats.
So, working memory--that is, the need to learn something, store the memory, retrieve the memory, and then do something new with the memory--was where estrogen made the difference. (21) And it isn't just that rats feel better, get better sleep, and don't suffer little ratty hot flashes before they're running the radial arm maze. They tried testing this by giving the rats estrogen only AFTER they ran the maze--so how they felt before and during the maze wouldn't make any difference. The rats who took estrogen afterward were far better at remembering what they'd done in the maze.(20)
They're starting to test working memory in women and the estrogen difference is starting to show up much more clearly in the human tests too. The more women have to use working memory (storing, maintaining, retrieving, and manipulating information), the clearer it is that estrogen makes a difference.(23) In a working memory test using spatial memory, women with no HRT made 40% more errors than women on either estrogen alone or estrogen and progestin.(23)
One easy example of the difference between memory and working memory is the digit ordering test. The first test is simple memory. The testers read a list of numbers. You repeat the numbers in the same order back to them. Information in and information out. Most of the time, there isn't much difference between the women on estrogen and the women who aren't. But the second test is working memory. They read you a list of numbers. After awhile, you have to repeat the list of numbers backward, which means you have to retrieve it and then think through how to reverse the order. This is where women on estrogen make fewer errors.(23)
Though most of the story of neurotransmitters will be told in the article on Hormones and Mood, the neurotransmitters play a big part in brain fog too. This isn't an accident that these are connected. Emotion and memory are closely related, which makes practical sense. Something that makes you afraid you want to remember to avoid in the future, and something that makes you happy you want to remember to find again.(5) The more intense the emotion, the more vivid the memory.
Serotonin and General Improvement
Estrogen increases serotonin levels both by helping make it and by keeping it in circulation (27). Estrogen also increases places in the frontal cortex (chimp brain) where serotonin can attach by 40%. (23, 17) Serotonin is central to sleep regulation, which obviously helps brain fog.(35) When levels are low, speech is slower and there's less ability to feel pleasure. With less emotion, there is less memory storage. Really low levels are associated with cognitive disorders, that is, trouble perceiving reality. (36)
Norepinephrine and Attention
Norepinephrine is also boosted by estrogen, though it appears most often in the reptile part of the brain--the basics of blood pressure and body temperature. (35) Its importance to brain fog is that it lets us become alert, focused, and oriented. (16, 36) It even works both ways. Lower norepinephrine makes hormones less effective. If norepinephrine levels are lowered, there are fewer estrogen receptors in the hypothalamus and estrogen can't boost progesterone receptors. (27)
Dopamine, Memory, and Coherent Thought
Dopamine is more often seen in the cortex or chimp brain, particularly the frontal lobe, which regulates the flow of information. Without dopamine, thoughts are incoherent and disrupted. (36) It also affects short-term and working memory tasks. (23, 21) Low dopamine plays a role in Parkinson's and schizophrenic patients. (36) Estrogen increases dopamine neurotransmission (27) but also works against dopamine, (6) so this is a case where progesterone balance is important.
Acetylcholine and Alzheimer's Disease
But the most important neurotransmitter for brain function that is affected by HRT has to be acetylcholine. It was the first neurotransmitter that they discovered. It acts on more than 10% of nerves in the body, but it's very important to the hippocampus and the prefrontal cortex--the places where memories are made and memories are stored. (4, 20) They know that drugs that work against acetylcholine block learning and memory. But even more, they've learned that Alzheimer's is associated with a 90% loss of the brain's production of acetylcholine. (16) Estrogen increases the levels of an enzyme needed to synthesize actylcholine (7, 17) They know that continuous long-term use of HRT is associated with lower odds of getting Alzheimer's (4, 17); in fact it might be as much as a 50% drop in risk, which is the same as delaying the start of Alzheimer's by five years (18). They've shown that blood levels of estrogen are lower in women with Alzheimer's. (17) But when estrogen is given to women who already have the disease, there seems to be little or no benefit.(17) So, they have to find out more about how it works. They wouldn't prescribe HRT just to prevent Alzheimer's at this time, but it seems to be a real benefit.
There is an area where estrogen may cause problems. There is a definite increase in seizures with estrogen, perhaps because there is so much more going on that it forms an electrical storm in the brain.(5) Progesterone inhibits the excitement that estrogen creates, so balance is crucial. Hormones don't cause seizures but influence how often they happen. (38)
Window of Opportunity
There are some researchers who believe that, as with osteoporosis, there is a window of opportunity right at menopause, when HRT can make a big difference. So the sooner after oopherectomy or menopause that you start it, the better.(4) Only six days after an oopherectomy, rats without estrogen were already losing many synapses.(32)
This might explain the reason that the Alzheimer's studies don't agree. If you start HRT late, then you don't get the good effects.(4) There was one study that might support this idea--of women with an average age of 81 who did no better than women on a placebo in memory tests. But the women started the HRT late and the tests were very easy (so a difference between groups was hard to measure). (40) This window of opportunity theory might also explain the contradictions between the fact that many studies have shown that HRT reduces the chance of dying from a stroke by 20% to 60%, and yet a recent placebo-controlled study showed that starting estrogen didn't help older women who had already had a stroke. (47)
Difference between Premarin and Other Estrogens
In choosing HRT with brain function in mind, it might be better to go with simple estradiol (patches, creams, Estrace) than with Premarin (27 different steroids and a high percentage of estrone). There may be a difference in how they act in the brain. There was a study of brain function that was comparing Estratest, Premarin (CEE), and esterified estradiol (EE). To the researchers' surprise, women on EE did better than women on CEE on certain tests. Apparently, CEE and EE affect frontal lobe (chimp brain) function differently. Not only did the women do differently on the tests, but imaging showed the patterns of blood flow in the brain were different. (28)
Here is another case where the ratio of progesterone to estrogen may be crucial (27) Progesterone in general decreases estrogen's good effects, but it actually increases estrogen's good effects in the hippocampus.(9) In working memory, one study found that there was no difference between estrogen vs. estrogen and progesterone. (23) Progesterone acts very differently in different people so it's hard to predict (18) but it can slow some verbal recall. Cream might be better than oral for brain function.(18) Progesterone and related chemicals (which are higher when you use oral) can actually be produced in the brain, so a little might go a long way. One of the related chemicals can produce fatigue, confusion, and problems with immediate recall (27) but another has the opposite effect. (27) This is why progesterone is so unpredictable.
The primary role testosterone plays in brain function in men is turning into estrogen. (6) But testosterone does have its own receptors.(18) It seems to improve visual and spatial skills and a better grasp of patterns and locations.(3, 18, 19) Women, especially women after oopherectomy, report that it improves brain function, but as one researcher said, there's a "resounding lack of evidence" right now on what testosterone does in the brain.(27)
SERMs or "designer estrogens" may be an important choice--in the future. Unfortunately, the drugs currently available don't seem to have much effect on the brain. The reason they are excited about "designing" estrogens is that they've just discovered that there are two kinds of estrogen receptors, alpha and beta. These receptors can have opposite effects, which is why it's so confusing to figure out whether you have too much or too little estrogen. (31) They think that they can develop SERMs that work on only one kind of receptor and produce only the effects they want. (48)
SOME NONHORMONAL AIDS TO BRAIN FUNCTION
Exercise is of course the best thing to do. It increases blood circulation, which we want. (2) Exercise, especially outdoors, increases serotonin levels. (36)
Adequate Protein (60 grams a day)
Almost all the neurotransmitters are created from essential amino acids--that is, nutrients found in whole protein that we can't make ourselves. So you have to give the body the building blocks it needs. (35) In particular, it's good to boost tryptophan, the precursor of serotonin and melatonin. It's found in turkey and the malt in Ovaltine (great for helping with sleep). Bananas and plums are also supposed to be good for serotonin levels. (36)
Gingko has been proven effective against Alzheimer's Disease and against normal age-related memory loss. They aren't sure why. They thought it was because it's a blood thinner, but it's something else operating on the nerve cells themselves to protect nerve cell health, not unlike estrogen.(49)
Estrogen decreases magnesium levels so this is important for women in both the Jungle and the Desert. Magnesium is necessary for the transmission of nerve impulses (in addition to all the other good things it does)..
B6 is essential to make serotonin, norepinephrine, and acetylcholine, so getting enough is important. Lack of (or too much of) vitamin B6 can lead to nerve inflammation.
Vitamin B12 is necessary to the normal activity of brain cells and works with B6 and folate. It gets harder to get from food with age and problems with stomach acid. (49)
Smoking causes all kinds of problems in the Hormone Jungle, but it interferes with acetylcholine and dopamine in particular and with oxygen and the blood's ability to circulate right.(35)
Statins lower cholesterol, which helps with blood circulation, and statins help with Alzheimer's Disease.
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15. J. F. Cryan et al. Use of dopamnine beta hydroxylase deficient mice to determen the role of norepinephrine in the mechanism of action of antidepressant drugs. 2001 Journla of Pharmacological Experimental Therapy 298:651-657.
16. Department of Pscyhology, California State University at Chico.
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19. Miles, C., et al. 1998. Estrogen and memory in a transsexual population. Hormones and Behavior 34:199-208.
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21 Luine, V. N. et al. 1998. Estradiol enhances learning and memory in a spatial memory task and efects levels of monoaminergic neurotransmitters. Hormones and Behavior 34:149-162.
22. Kimura, D. 1995. Estrogen replacemnt therapy may protect against intellectual decline in postmenopausal women. Hormones and Behavior 29:312-321.
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24. Bashford, R. A. and J. P. Horrigan. 2000. Progesterone organogel for premenstrual dysphoric disorder. Journal of the American Academy of Child and Adolescent Psychiatry 39:546-547.
25. Bloch, M, et al. 2000. Effects of gonadal steroids in women with a history of postpartum depression. American Journal of Psychiatry 157: 924-930.
26. Mitchell, E. S., and N. F. Woods. 2001. Midlife women's attributions about perceived memory changes: observations from the Seattle midlife women's health study. Journal of Women's Health and Gender-based Medicine. 10:351-362.
27. Epperson, C. N. et al. 1999. Gonadal Steroids in the treatment of mood disorders. Psychosomatic Medicine 61:676-689.
28. Friebely, J. S. et al. 2001. Preliminary observations on differing psychological effects of conjugated and esterified estrogen treatments. Journal of Women's Health and Gender-based medicine 10:181-187.
29. Shaver, J. L. F., and S. N. Zenk. 2000. Sleep disturbance in menopause. Journal of Women's Health and Gender-based Medicine 9:109-118.
30. Singh, M. et al. 1999. Estrogen induced activation of mitogen activated protein kinase in cerebral cortical expalnts: convergence of estrogen and neurotrophin signaling pathways. Journal of Neuroscience 19:1179-1188.
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32. miller, M. M. et al. 1998. Estrogen, the ovary, and the neurotransmitters: factors associated with aging. Experimental Gerontology 33:729-757.
33. Eckersell, C. B., and P. E. Micevych. 1997. Opiate receptors modulate estrogen induced cholecystokinin and tachykinin but not enkephalin messenger RNA levels in the limbic system and hypothalamus. Neuroscience 80:473-485.
34. Hiemke, C., et al. 1992. Actions of sex hormones in the brain. Progress in Neuro-Psychopharmacology and biological Psychiatry 16:377-388.
35. Moses, P. L. 1997. Quick and dirty guide to neurotransmitters. http://pages.prodigy.net/paolom/Misc/Q+D.htm.
36. "Wellbeing Neurotransmitters." 5 Star Health. http://www.5starhealth.com/depression/wellbeing.html.
37. "Brain chemistry, a crash course." 5 Star Health. http://www.5starhealth.com/depression/chemistry.html
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39. Vande Kar, L. D. Research on serotonergic regulation of the hypothalamic neuroendocrine systems. http://www.meddean.luc.edu/lumen/Dep...rm/VDKWEB.htm.
40. Shaywitz, S. E. et al. 1999. Effect of estrogen on brain activation patterns in postmenopausal women during working memory tasks. JAMA 281:1197-1202.
41. Binder, E. F. et al. 2001. Effects of hormone replacement therapy on cognitive performance in elderly women. Maturitas 38:137-146.
42. De Leo, V. et al 2001. Evaluation of combining kava extract with hormone replacement therapy in the treatment of postmenopausal anxiety. Maturitas 39:185-188.
43. Mann, D. 2001. Dotors target two brain chemicals to treat depression, anxiety. WebMd Medical News. 9/17
44. Schorr, M. High fat diets trigger changes in brain chemistry. Reuters Newsline 9/13/2001.
45. Lee, K. A., et al. 2000. REM sleep and mood state in childbearing women: sleepy or weepy? Sleep 23:877-885.
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48. Journal of Applied Physiology 2001, November.
49. The Natural Pharmacist. www.tnp.com <http://www.tnp.com> .
This content was written by staff of HysterSisters.com by non-medical professionals based on discussions, resources and input from other patients for the purpose of patient-to-patient support.
feel real good
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The HysterSisters June newsletter has been published and can be accessed on the website here: June 2013 HysterSisters Ch [More