I have a patient who worked as a day trader. You've got to have the metaphorical equivalent of certain male parts to do this kind of work--remaining focused, aggressive, and ruthless in a high stakes, high stress undertaking. She came to me because her world as day trader had fallen apart with the onset of menopause. When the market crashed in early October, 2008, she reported that she'd sat frozen in front of her computer, knowing that she needed to react and regroup yet unable to do anything but watch the debacle.
"You have to understand." she said with uncharacteristic (for her) tears in her eyes, "This was not me."
She proceeded to tell me about other pre-menopausal activities that had been her, namely extreme sports and risky jobs the likes of which I never once considered as options for my cautious self. Yet despite these major changes brought on by diminishing levels of estrogen, her gynecologist declined her request to consider estrogen therapy; she was not, after all, experiencing hot flashes.
One of the best kept secrets about the myriad of changes brought on by menopause is the profound effects that the loss of estrogen has on the brain. There is no doubt that some women do just fine in cognitive and emotional ways through menopause and beyond, but many do not. When my patients report that they are "doing just fine" post-periods, I always ask "How's your mood" and "How's your memory?". Not unusual, then, for me to uncover evidence that, in fact, they are not doing just fine at all.
If you are interested in hearing more about making the complex decisions involved on the road to our 600 month birthdays and beyond, please consider joining me for a menopause workshop on June 5th from 10:30 to noon at my Denver office. Please call 303-393-0300 to register; the non-refundable $20 fee is due at the time you sign-up. You do not need to be my patient to attend. If this topic is of interest to you but June 5th is a no-go, leave your name and number with my staff, and we will contact you with dates later in the summer when I will present the same material.
Showing posts with label Estrogen and memory. Show all posts
Showing posts with label Estrogen and memory. Show all posts
Sunday, May 23, 2010
Saturday, May 8, 2010
Hippocampal volume, aging, and estrogen
If you're reading this blog, chances are good that you have some concerns about your aging brain. You are certainly not alone; I often field questions and complaints about decreasing memory function associated with advancing years.
The most common memory-related issue is the most difficult to assess, namely when is it time to worry, when does forgetful cross the boundary from normal to pathological. If we set cognitive normal at the level at which one's doctor functions, regular readers and my patients know that I would be inclined to overlook verbal slips and frequent loss of keys and reading glasses as a normal response to aging, stress, and general busyness.
In fact, neurologists have defined mild cognitive impairment or MCI as "a transitional state between the cognitive changes of normal aging and very early dementia"(1) that progresses to full-scale dementia such as Alzheimer's Disease at the rate of 10-16% per year. Well, that's not very helpful because, once again, we're stuck with the question of 'what's normal?' Researchers have stepped forward with clarification that's more or less helpful, citing the following characteristics of MCI:
Distinguishing so-called normal aging from MCI is, therefore, a bit slippery. One not-ready-for-prime-time technique that identifies slightly confused MCI types at high risk for dementia is the use of MRI brain imaging to measure the size of the hippocampus. This little brain structure sits to the inside of our temporal lobes located just above our ears and is so-named because it's shaped like a seahorse (but NOT like a hippo!). The hippocampus functions as VP in charge of memory formation. Along with everything else in the human body, these centers tend to shrink with age especially in those on the road to dementia. Rochester researchers launched a multi-disciplinary effort between neurologists, psychiatrists, and radiologists to see if measurements of the hippocampi of elderly test subjects with MCI reliably predicted who ended up dazed and confused at the end of nearly three years of observation(2).
In short, it did. The researchers adjusted for head size by computing the volume of the hippocampi as a function of total brain volume, and they compared the size of the subjects' memory centers to a previously studied group of elderly controls with normal mental functioning. A subject with an average hunk of hippocampus received a W score of zero whereas those with itty bitty hippocampi were assigned negative W scores.
The lower a subject's W score, the more likely they were to slip from MCI unto dementia. Those with W scores greater than zero, i.e. endowed with robust hippocampi, progressed to Alzheimer's Disease (AD) at the rate of 15% by study's end which is an average rate of progression as determined by numerous previous studies. On the other hand, among those with itty bitty hippocampi--W scores less than -2.5 which represents a memory center in the 1st percentile of normal size--50% were diagnosed with AD by study's end.
So where does estrogen therapy fit in? This hormone is known to promote neuronal repair and growth, causing rat hippocampal neurons to fairly bristle with spiky connections from one cell to the next. And the more hippocampal neurons connect with one another, the better the rat performs at various rat tricks!
For humans, however, in whom brain biopsies are considered bad form in every venue but TV episodes of House, M.D., MRI imaging was used to measure the size of hippocampi in the brains of post-menopausal women, some on hormones and some without. Researchers found a positive effect on hippocampal size associated with the use of estrogen. But this benefit was not seen in subjects enrolled in the Women's Health Initiative Memory Study who initiated hormone replacement for the first time years past menopause. This disparate effect of estrogen on memory as correlated with the timing of therapy relative to the onset of menopause suggests once again that there is a window of opportunity after which estrogen no longer preserves brain function.
_____
(1)Grundman M, et al. Mild Cognitive Impairment Can Be Distinguished From AlzheimerDisease and Normal Aging for Clinical Trials. Arch Neurol. 2004;61:59-66.
(2) Clifford, R, et al. Prediction of AD with MRI-Based Hippocampal Volume in Mild Cognitive Impairment. Neurology. 1999 April 22; 52(7): 1397-1403.
The most common memory-related issue is the most difficult to assess, namely when is it time to worry, when does forgetful cross the boundary from normal to pathological. If we set cognitive normal at the level at which one's doctor functions, regular readers and my patients know that I would be inclined to overlook verbal slips and frequent loss of keys and reading glasses as a normal response to aging, stress, and general busyness.
In fact, neurologists have defined mild cognitive impairment or MCI as "a transitional state between the cognitive changes of normal aging and very early dementia"(1) that progresses to full-scale dementia such as Alzheimer's Disease at the rate of 10-16% per year. Well, that's not very helpful because, once again, we're stuck with the question of 'what's normal?' Researchers have stepped forward with clarification that's more or less helpful, citing the following characteristics of MCI:
- Memory complaint preferably confirmed by another person
- Objective memory impairment with a standardized assessment tool
- Normal general cognitive functioning
- Intact activities of daily living
- Not demented
Distinguishing so-called normal aging from MCI is, therefore, a bit slippery. One not-ready-for-prime-time technique that identifies slightly confused MCI types at high risk for dementia is the use of MRI brain imaging to measure the size of the hippocampus. This little brain structure sits to the inside of our temporal lobes located just above our ears and is so-named because it's shaped like a seahorse (but NOT like a hippo!). The hippocampus functions as VP in charge of memory formation. Along with everything else in the human body, these centers tend to shrink with age especially in those on the road to dementia. Rochester researchers launched a multi-disciplinary effort between neurologists, psychiatrists, and radiologists to see if measurements of the hippocampi of elderly test subjects with MCI reliably predicted who ended up dazed and confused at the end of nearly three years of observation(2).
In short, it did. The researchers adjusted for head size by computing the volume of the hippocampi as a function of total brain volume, and they compared the size of the subjects' memory centers to a previously studied group of elderly controls with normal mental functioning. A subject with an average hunk of hippocampus received a W score of zero whereas those with itty bitty hippocampi were assigned negative W scores.
The lower a subject's W score, the more likely they were to slip from MCI unto dementia. Those with W scores greater than zero, i.e. endowed with robust hippocampi, progressed to Alzheimer's Disease (AD) at the rate of 15% by study's end which is an average rate of progression as determined by numerous previous studies. On the other hand, among those with itty bitty hippocampi--W scores less than -2.5 which represents a memory center in the 1st percentile of normal size--50% were diagnosed with AD by study's end.
So where does estrogen therapy fit in? This hormone is known to promote neuronal repair and growth, causing rat hippocampal neurons to fairly bristle with spiky connections from one cell to the next. And the more hippocampal neurons connect with one another, the better the rat performs at various rat tricks!
For humans, however, in whom brain biopsies are considered bad form in every venue but TV episodes of House, M.D., MRI imaging was used to measure the size of hippocampi in the brains of post-menopausal women, some on hormones and some without. Researchers found a positive effect on hippocampal size associated with the use of estrogen. But this benefit was not seen in subjects enrolled in the Women's Health Initiative Memory Study who initiated hormone replacement for the first time years past menopause. This disparate effect of estrogen on memory as correlated with the timing of therapy relative to the onset of menopause suggests once again that there is a window of opportunity after which estrogen no longer preserves brain function.
_____
(1)Grundman M, et al. Mild Cognitive Impairment Can Be Distinguished From AlzheimerDisease and Normal Aging for Clinical Trials. Arch Neurol. 2004;61:59-66.
(2) Clifford, R, et al. Prediction of AD with MRI-Based Hippocampal Volume in Mild Cognitive Impairment. Neurology. 1999 April 22; 52(7): 1397-1403.
Sunday, May 2, 2010
Old ladies and verbal fluency
My last post covered data on the brain health of women abruptly plunged into menopause via bilateral oophorectomies (removal of ovaries), some of whom received post-op estrogen and some of whom did not. On average, those who did fared better in cognition as they motored on in life than those who did not.
So what about ladies who just fade into senescence in a non-surgical sort of way? Well, no paucity of info on that subject either. Consider the Research into Memory, Brain function and Estrogen Replacement study--more familiarly known as the REMEMBER study--where 428 Australian old ladies were enticed down to an Adelaide research center and put through their paces.(1)
How do you know which old Australian is still on her game? Among other things, you see who is fastest on the FAS test. This is a measure of verbal fluency which requires the subject to say as many words as they can think of that start with the letter F, then A, then S in 60 second testing intervals. The doctors down under tried this very task--among other tests-- on the subjects, comparing FAS scores amongst the ladies as associated with their early, late, or never use of estrogen through the golden years of menopause.
The old gals who gravitated to estrogen with that first hot flash bested the rest in FAS facility. Compared to these so-called "early initiators," the never users were not so FASt. But oy, the "late initiators," i.e. those Jills-come-lately to hormone therapy who decided to estrogen up after age 56 or five or more years post-oophorectomy; this group was slowest of all on the word retrieval thing.
These findings mirror those of the WHIMS study wherein women who were older than 67 at the onset of the Women's Health Initiative study were put on full dose Premarin and Provera many, many years post-menopause, thus qualifying as "late-late initiators". This sub-study of the WHI followed the group for the onset of cognitive troubles over the ensuing five years. When compared with a control group given look-alike placebo Premarin, this study group demonstrated significantly more problems retaining their marbles during follow-up.
All this research suggests again a 'window of opportunity' with respect to bolstering aging brains through the use of estrogen, the so-called timing hypothesis proposed by neuroscientists. If the brain, particularly the structures of the forebrain in charge of complex cognition, is full of estrogen receptors, why would it matter when hormone therapy is initiated?
More info to follow!
_____
(1) MacLennan, AH, et al. Hormone therapy, timing of initiation, and cognition in women aged older than 60 years: the REMEMBER pilot study. Menopause. 2006 Jan-Feb;13(1):28-36.
So what about ladies who just fade into senescence in a non-surgical sort of way? Well, no paucity of info on that subject either. Consider the Research into Memory, Brain function and Estrogen Replacement study--more familiarly known as the REMEMBER study--where 428 Australian old ladies were enticed down to an Adelaide research center and put through their paces.(1)
How do you know which old Australian is still on her game? Among other things, you see who is fastest on the FAS test. This is a measure of verbal fluency which requires the subject to say as many words as they can think of that start with the letter F, then A, then S in 60 second testing intervals. The doctors down under tried this very task--among other tests-- on the subjects, comparing FAS scores amongst the ladies as associated with their early, late, or never use of estrogen through the golden years of menopause.
The old gals who gravitated to estrogen with that first hot flash bested the rest in FAS facility. Compared to these so-called "early initiators," the never users were not so FASt. But oy, the "late initiators," i.e. those Jills-come-lately to hormone therapy who decided to estrogen up after age 56 or five or more years post-oophorectomy; this group was slowest of all on the word retrieval thing.
These findings mirror those of the WHIMS study wherein women who were older than 67 at the onset of the Women's Health Initiative study were put on full dose Premarin and Provera many, many years post-menopause, thus qualifying as "late-late initiators". This sub-study of the WHI followed the group for the onset of cognitive troubles over the ensuing five years. When compared with a control group given look-alike placebo Premarin, this study group demonstrated significantly more problems retaining their marbles during follow-up.
All this research suggests again a 'window of opportunity' with respect to bolstering aging brains through the use of estrogen, the so-called timing hypothesis proposed by neuroscientists. If the brain, particularly the structures of the forebrain in charge of complex cognition, is full of estrogen receptors, why would it matter when hormone therapy is initiated?
More info to follow!
_____
(1) MacLennan, AH, et al. Hormone therapy, timing of initiation, and cognition in women aged older than 60 years: the REMEMBER pilot study. Menopause. 2006 Jan-Feb;13(1):28-36.
Saturday, May 1, 2010
Window of Opportunity of Estrogen Therapy for Neuroprotection
Catchy title for a workshop, no? It certainly caught my eye, but alas it was over and done with months ago, and I only heard about it this month.
Not too late, however, for me to share the gist of the message with you, namely that there is ample evidence that estrogen is brain protective--i.e. can decrease your risk of progressing from the occasional menopause moment into a permanent demented state of mind as the years go by--but only if estrogen supplementation is initiated at a time when your brain is still functioning normally.
Actually, this is not new news at all. Researchers have known for years that estrogen plays a critical role in brain function, particularly in those parts of the anterior brain known as the forebrain where memories are formed and complex functions such as learning and multi-tasking are initiated. Diminishing estrogen levels during that lovely adventure known as perimenopause are, therefore, often associated with problems in verbal memory (finding the right word at the right time and using it correctly) as well as difficulty in mastering new skills. Ever tried to teach an old lady how to use e-mail? And if you've spent any time in nursing homes, you are well aware that the majority of the residents are female and a large number of them are struggling with dementia.*
Doctors at the Mayo Clinic studied women who underwent oophorectomies (removal of one or both ovaries) before the age of menopause and compared their brain health through the years following surgery as compared with a group of subjects who hung onto their ovaries through a natural menopause.(1) Removing the ovaries at the time of a hysterectomy done for any reason (such as fibroids or abnormal menstrual bleeding) used to be a common practice in order to protect against the possibility of future ovarian cancer. Since the findings of the Women's Health Initiative made headline news in 2002, the use of estrogen therapy following such surgery has become increasingly uncommon.
Those women who underwent bilateral oophorectomy (both ovaries removed) before menopause were 1.5 times more likely to develop dementia as they aged than the control subjects who did not undergo surgery. And the younger the age at which they experienced loss of ovarian function (and thus loss of estrogen), the more likely they were to develop profound problems with cognitive functioning. Subsequent analysis of the data from the Mayo Clinic group as well as from other studies showed that oophorectomized women who received estrogen therapy until age 50--more or less the time of natural menopause--had a normal risk of dementia.(2) In other words, they were no more likely to develop Alzheimer's disease than women going through menopause in the normal fashion. Furthermore, menopausal women who took hormone therapy initiated at the time of menopause and continued for 10 years, i.e. from ages 50-60, had a reduced risk of dementia.
The scary news, however, regarding hormone therapy and dementia, came from the Women's Health Initiative which looked at the health effects of hormone supplementation in a group of post-menopausal women with an average age of 63 many of whom were a decade or more past menopause. The sub-study that looked at HRT and brain health called the Women's Health Initiative Memory Study (WHIMS) found that those women in the group who initiated HRT (and remember, this was a group specifically chosen for the characteristic that none of them had ever been on HRT prior to the study) years past menopause were significantly more likely to develop dementia.
Scientists have dubbed this the Timing Hypothesis of cognitive aging with respect to the protective qualities of estrogen. Take it early while your brain is still functioning normally, and it is protective. Take it later after you've begun to develop vascular changes from atherosclerosis or the protein plaques of Alzheimer's, and it not only won't protect, it might in fact accelerate the process.
More on the possible mechanisms for this dual effect of estrogen on brain tissue--protective early on and detrimental as aging progresses--in future posts.
_____
*Whereas the male residents, if there are any, are more than likely suffering from Parkinson's disease, a brain dysfunction much more common in men than women.
(1) Rocca, WA, et al. Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause. Neurology 2007 Sep 11;69(11):1074-83.
(2) Rocca, WA, et al. Oopherectomy, Menopause, Estrogen, and Brain Aging: The Timing Hypothesis. Neurodegenerative Disease.
Not too late, however, for me to share the gist of the message with you, namely that there is ample evidence that estrogen is brain protective--i.e. can decrease your risk of progressing from the occasional menopause moment into a permanent demented state of mind as the years go by--but only if estrogen supplementation is initiated at a time when your brain is still functioning normally.
Actually, this is not new news at all. Researchers have known for years that estrogen plays a critical role in brain function, particularly in those parts of the anterior brain known as the forebrain where memories are formed and complex functions such as learning and multi-tasking are initiated. Diminishing estrogen levels during that lovely adventure known as perimenopause are, therefore, often associated with problems in verbal memory (finding the right word at the right time and using it correctly) as well as difficulty in mastering new skills. Ever tried to teach an old lady how to use e-mail? And if you've spent any time in nursing homes, you are well aware that the majority of the residents are female and a large number of them are struggling with dementia.*
Doctors at the Mayo Clinic studied women who underwent oophorectomies (removal of one or both ovaries) before the age of menopause and compared their brain health through the years following surgery as compared with a group of subjects who hung onto their ovaries through a natural menopause.(1) Removing the ovaries at the time of a hysterectomy done for any reason (such as fibroids or abnormal menstrual bleeding) used to be a common practice in order to protect against the possibility of future ovarian cancer. Since the findings of the Women's Health Initiative made headline news in 2002, the use of estrogen therapy following such surgery has become increasingly uncommon.
Those women who underwent bilateral oophorectomy (both ovaries removed) before menopause were 1.5 times more likely to develop dementia as they aged than the control subjects who did not undergo surgery. And the younger the age at which they experienced loss of ovarian function (and thus loss of estrogen), the more likely they were to develop profound problems with cognitive functioning. Subsequent analysis of the data from the Mayo Clinic group as well as from other studies showed that oophorectomized women who received estrogen therapy until age 50--more or less the time of natural menopause--had a normal risk of dementia.(2) In other words, they were no more likely to develop Alzheimer's disease than women going through menopause in the normal fashion. Furthermore, menopausal women who took hormone therapy initiated at the time of menopause and continued for 10 years, i.e. from ages 50-60, had a reduced risk of dementia.
The scary news, however, regarding hormone therapy and dementia, came from the Women's Health Initiative which looked at the health effects of hormone supplementation in a group of post-menopausal women with an average age of 63 many of whom were a decade or more past menopause. The sub-study that looked at HRT and brain health called the Women's Health Initiative Memory Study (WHIMS) found that those women in the group who initiated HRT (and remember, this was a group specifically chosen for the characteristic that none of them had ever been on HRT prior to the study) years past menopause were significantly more likely to develop dementia.
Scientists have dubbed this the Timing Hypothesis of cognitive aging with respect to the protective qualities of estrogen. Take it early while your brain is still functioning normally, and it is protective. Take it later after you've begun to develop vascular changes from atherosclerosis or the protein plaques of Alzheimer's, and it not only won't protect, it might in fact accelerate the process.
More on the possible mechanisms for this dual effect of estrogen on brain tissue--protective early on and detrimental as aging progresses--in future posts.
_____
*Whereas the male residents, if there are any, are more than likely suffering from Parkinson's disease, a brain dysfunction much more common in men than women.
(1) Rocca, WA, et al. Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause. Neurology 2007 Sep 11;69(11):1074-83.
(2) Rocca, WA, et al. Oopherectomy, Menopause, Estrogen, and Brain Aging: The Timing Hypothesis. Neurodegenerative Disease.
Tuesday, August 19, 2008
Estrogen and memory function
A study conducted at the University of Southern California demonstrated that estrogen promotes the growth of those essential neurons in the brain's hippocampus that are critical to memory function. Scientists there created a hippocampal campus in a petri dish, inducing these cells from the memory center to set up housekeeping in the USC lab. They then squirted conjugated equine estrogens (CEEs or Premarin) on the nerve cell colonies and watched the results under a videomicroscope.
The cells literally bristled with excitement. The addition of estrogen juice significantly increased the number of dendrites or outgrowths of the cell membranes which are known to be cellular markers of memory formation. Dendrites hook-up with other neurons to form new connections, a process that promotes brain 'plasticity' or the ability to learn new material and make new associations. In other words, the same cellular events that occur in the hippocampus of the brain during memory formation happened in these brain cell cultures when estrogen was added.
When I see patients going through the menopausal transition, I not only inquire about hot flashes, night sweats, and the quality of their sleep, I also ask "How's your mood?" and "How's your memory?". The lack of estrogen affects women differently, some struggling far more than others in a brain function sense. I think the problems with verbal memory and executive functioning (starting a multi-step task and completing it successfully) along with the increase in anxiety and depression that can accompany falling estrogen levels are too often not addressed in women of age.
The cells literally bristled with excitement. The addition of estrogen juice significantly increased the number of dendrites or outgrowths of the cell membranes which are known to be cellular markers of memory formation. Dendrites hook-up with other neurons to form new connections, a process that promotes brain 'plasticity' or the ability to learn new material and make new associations. In other words, the same cellular events that occur in the hippocampus of the brain during memory formation happened in these brain cell cultures when estrogen was added.
When I see patients going through the menopausal transition, I not only inquire about hot flashes, night sweats, and the quality of their sleep, I also ask "How's your mood?" and "How's your memory?". The lack of estrogen affects women differently, some struggling far more than others in a brain function sense. I think the problems with verbal memory and executive functioning (starting a multi-step task and completing it successfully) along with the increase in anxiety and depression that can accompany falling estrogen levels are too often not addressed in women of age.
Friday, June 20, 2008
PET scans prove that neurons like estrogen
We now have several lines of evidence, from independent parts of the brain, that estrogen is actually protective in a manner that is related to aging and dementia.
---Daniel Silverman, MD, head of neuronuclear imaging at UCLA
Scads of research evidence already support this conclusion. Reports from brain cells in petri dishes, as well as testimonials from aging gerbils, mice, rats, and women attest to the beneficial effects of estrogen with respect to forming new memories, learning new tasks, finding the right word at the right time, and completing a multi-step task(1) from start to finish.
UCLA scientists used functional brain imaging to visualize how well postmenopausal brains worked with estrogen compared to their activity after estrogen is withdrawn(2). PET scanning involves administration of 'tagged glucose' molecules. When busy little neurons put on their thinking caps in your brain, they suck up and metabolize sugar at an accelerated rate. The labeled glucose glows like a light bulb on subsequent scanning, identifying those parts of the brain that are successively at work.
81 women considered to be at high risk for Alzheimer's disease (AD) based on family history or genetic testing entered the study. All were initially on estrogen for menopausal symptoms. Baseline PET scans were performed, then the subjects were randomly assigned to continue estrogen or go on placebo over 2 years of follow-up. Intial "findings from the first 25 women to undergo baseline and follow-up scans were highly consistent for a neuroprotective effect of estrogen," per Dr. Silverman.
The initial scans showed that the longer the woman had been exposed to her own estrogen (defined as years from onset of menstruation to the end of the line at menopause), the higher the metabolism in the precuneus area of the posterior medial cortex. Don't knock the precuneus area just because you--and me!--haven't a clue where or what it is. Significantly diminished blood flow to this area is one of the earliest signs of Alzeimer's disease.
By study's end, women on estrogen continued to light up brain regions known to be most affected by AD whereas lights were dimming for the estrogenless group. Activity in the right inferior parietal lobe decreased twice as fast for this befuddled group. Research suggests that the right IPL is involved in the "what" (...did I come for) and "where" (...did I put it) of working memory. In fact, again per Silverman: "In [some] women who stayed on estrogen, metabolic activity in the frontal part of the cortex actually increased."
_____
(1)Such as walking from one room to another to get something, grabbing that something, and returning with it to the original room with the thought intact as to why you wanted that thing
(2)Silverman, D et al. Society of Nuclear Medicine 2008 Annual Meeting: Abstract 973. Presented June 16, 2008.
---Daniel Silverman, MD, head of neuronuclear imaging at UCLA
Scads of research evidence already support this conclusion. Reports from brain cells in petri dishes, as well as testimonials from aging gerbils, mice, rats, and women attest to the beneficial effects of estrogen with respect to forming new memories, learning new tasks, finding the right word at the right time, and completing a multi-step task(1) from start to finish.
UCLA scientists used functional brain imaging to visualize how well postmenopausal brains worked with estrogen compared to their activity after estrogen is withdrawn(2). PET scanning involves administration of 'tagged glucose' molecules. When busy little neurons put on their thinking caps in your brain, they suck up and metabolize sugar at an accelerated rate. The labeled glucose glows like a light bulb on subsequent scanning, identifying those parts of the brain that are successively at work.
81 women considered to be at high risk for Alzheimer's disease (AD) based on family history or genetic testing entered the study. All were initially on estrogen for menopausal symptoms. Baseline PET scans were performed, then the subjects were randomly assigned to continue estrogen or go on placebo over 2 years of follow-up. Intial "findings from the first 25 women to undergo baseline and follow-up scans were highly consistent for a neuroprotective effect of estrogen," per Dr. Silverman.
The initial scans showed that the longer the woman had been exposed to her own estrogen (defined as years from onset of menstruation to the end of the line at menopause), the higher the metabolism in the precuneus area of the posterior medial cortex. Don't knock the precuneus area just because you--and me!--haven't a clue where or what it is. Significantly diminished blood flow to this area is one of the earliest signs of Alzeimer's disease.
By study's end, women on estrogen continued to light up brain regions known to be most affected by AD whereas lights were dimming for the estrogenless group. Activity in the right inferior parietal lobe decreased twice as fast for this befuddled group. Research suggests that the right IPL is involved in the "what" (...did I come for) and "where" (...did I put it) of working memory. In fact, again per Silverman: "In [some] women who stayed on estrogen, metabolic activity in the frontal part of the cortex actually increased."
_____
(1)Such as walking from one room to another to get something, grabbing that something, and returning with it to the original room with the thought intact as to why you wanted that thing
(2)Silverman, D et al. Society of Nuclear Medicine 2008 Annual Meeting: Abstract 973. Presented June 16, 2008.
Wednesday, June 4, 2008
Verbal fluency and hormone therapy
Verbal fluency is defined as the ability to find the right word at the right time and use it with ease when appropriate. I wrote a post on it earlier this year on Doc of Ages, my other blog.
I got an interesting comment and question on the subject today. Verbal fluency (VF) is very much an estrogen-supported brain function. Out of estrogen and you may be out of luck with respect to having your say in an okay way. This lady writes:
In the last few years I have noticed what seems to me more VF problems than my friends. I am not as bothered by it when writing which I do a great deal.
I'm 73 and have taken Premarin, .625 mg daily, since I had a complete hysterectomy at age 54 (done for multiple non-malignant reasons). Some doctors lately say I should discontinue the Premarin because it increases my likelihood of getting cancer - uterine and breast - and major clots. (I had bilateral mastectomies in my 30s for major non-malignant breast changes and a high family cancer history). I am healthy otherwise (minor heart change, excellent bone density, some arthritis).
Two questions: Why the VF problem? Discontinue the Premarin? The answers I get are vague and don't satisfy me.
I answered:
While VF is sensitive to estrogen or the lack thereof, it also falls off with age. That said, you're not that old, and I never know what to make of this citation of age as a reason for anything; it seems that there must always be an underlying problem that perhaps worsens with age but not explained by age alone. As VF is a frontal lobe function, and the frontal lobe is more susceptible to stroke damage than other parts of the brain, I wonder if you should have an MRI to look for the tiny white spots that correlate with small vessel disease in the brain.
Premarin or no, here's my take on that. While estrogen is known to support frontal lobe function, oral estrogen supplements, and in particular Premarin taken orally, are known to cause some problems even as they may benefit brain function.
Once orally-ingested hormones are absorbed into the bloodstream, they head straight for the liver via the portal circulation. The liver gears up to break these foreign molecules down and, in doing so, produces some unwanted proteins such as angiotensinogen (which can raise blood pressure), C-reactive protein (which causes inflammation), clotting factors (which raise risk of clots and blood vessel inflammation) and triglycerides (which raise risk of heart disease and stroke).
If you haven't had a major clot from Premarin, you are unlikely to get one now unless you have to undergo major surgery such as a knee replacement. You don't have breasts or uterus to worry about cancer risk. But you do have to worry about stroke.
I would consider going off Premarin. But...estrogen supports frontal lobe function. You might consider replacing the Premarin with a transdermal estradiol patch such as Vivelle Dot. That way, the estrogen you take is not foreign (like the horse estrogens of Premarin) and it does not go through your liver (causing all the above troubles). It is known that transdermal estrogen does not raise clotting factors, C-reactive protein, or angiotensinogen. It has not been studied whether or not transdermal estrogen increases risk of stroke the way oral estrogen does, but logically it should not.
The only vague part of my information is whether or not you should change hormone delivery systems or go off it altogether. That is a weighted decision best made by yourself and your doctor.
I got an interesting comment and question on the subject today. Verbal fluency (VF) is very much an estrogen-supported brain function. Out of estrogen and you may be out of luck with respect to having your say in an okay way. This lady writes:
In the last few years I have noticed what seems to me more VF problems than my friends. I am not as bothered by it when writing which I do a great deal.
I'm 73 and have taken Premarin, .625 mg daily, since I had a complete hysterectomy at age 54 (done for multiple non-malignant reasons). Some doctors lately say I should discontinue the Premarin because it increases my likelihood of getting cancer - uterine and breast - and major clots. (I had bilateral mastectomies in my 30s for major non-malignant breast changes and a high family cancer history). I am healthy otherwise (minor heart change, excellent bone density, some arthritis).
Two questions: Why the VF problem? Discontinue the Premarin? The answers I get are vague and don't satisfy me.
I answered:
While VF is sensitive to estrogen or the lack thereof, it also falls off with age. That said, you're not that old, and I never know what to make of this citation of age as a reason for anything; it seems that there must always be an underlying problem that perhaps worsens with age but not explained by age alone. As VF is a frontal lobe function, and the frontal lobe is more susceptible to stroke damage than other parts of the brain, I wonder if you should have an MRI to look for the tiny white spots that correlate with small vessel disease in the brain.
Premarin or no, here's my take on that. While estrogen is known to support frontal lobe function, oral estrogen supplements, and in particular Premarin taken orally, are known to cause some problems even as they may benefit brain function.
Once orally-ingested hormones are absorbed into the bloodstream, they head straight for the liver via the portal circulation. The liver gears up to break these foreign molecules down and, in doing so, produces some unwanted proteins such as angiotensinogen (which can raise blood pressure), C-reactive protein (which causes inflammation), clotting factors (which raise risk of clots and blood vessel inflammation) and triglycerides (which raise risk of heart disease and stroke).
If you haven't had a major clot from Premarin, you are unlikely to get one now unless you have to undergo major surgery such as a knee replacement. You don't have breasts or uterus to worry about cancer risk. But you do have to worry about stroke.
I would consider going off Premarin. But...estrogen supports frontal lobe function. You might consider replacing the Premarin with a transdermal estradiol patch such as Vivelle Dot. That way, the estrogen you take is not foreign (like the horse estrogens of Premarin) and it does not go through your liver (causing all the above troubles). It is known that transdermal estrogen does not raise clotting factors, C-reactive protein, or angiotensinogen. It has not been studied whether or not transdermal estrogen increases risk of stroke the way oral estrogen does, but logically it should not.
The only vague part of my information is whether or not you should change hormone delivery systems or go off it altogether. That is a weighted decision best made by yourself and your doctor.
Sunday, March 2, 2008
Exercise and estrogen
Lady rats discovered that exercise plus estrogen was the magic formula for keeping their memory for maze-running intact. This interaction of estrogen and physical activity on the cells of the hippocampus which is the memory center of the brain may be important for humans as well.
Brain-derived neurotrophic factor (BDNF) is a molecule recognized by neuroscientists for its role in nerve cell growth and repair. In particular, BDNF promotes the growth of dendrites or those little tree-branch-like projections off a nerve cell body that hook that cell up with its neighbors. The more those neurons connect one to another, the easier the flow of important information such as the next word and the next word in the sentence that you are speaking.
Animal studies suggest that in the presence of estrogen, happy neurons bristle with dendrites. And lots of dendrites in the hippocampus and the frontal lobe of your brain promotes, perhaps, the fluent flow of speech. Without estrogen, dendrites drop off neurons like the broken teeth of an old comb. Those left out of estrogen and low on dendrites may be left dazed and confused in the kitchen, wondering for what they came.
Back to our California rats. While physical activity increased their hippocampal BDNF, this exercise effect was reduced by a loss of estrogen in a time-dependent fashion. In other words, the longer the rats went without estrogen, the less brain benefits were derived from working out on the old exercise wheel. By the seventh estrogen-free week, exercise affected BDNF levels not at all. What's even worse, voluntary activity levels dropped off as well; those rats who were out of estrogen were disinclined to bustle about their cages for the sheer joy of mousy bustling.
Estrogen replacement then restored the rodents' BDNF back to normal levels. And hopping back on the workout wheel, in combination with long-term estrogen use, increased BDNF the most of all.
Brain-derived neurotrophic factor (BDNF) is a molecule recognized by neuroscientists for its role in nerve cell growth and repair. In particular, BDNF promotes the growth of dendrites or those little tree-branch-like projections off a nerve cell body that hook that cell up with its neighbors. The more those neurons connect one to another, the easier the flow of important information such as the next word and the next word in the sentence that you are speaking.
Animal studies suggest that in the presence of estrogen, happy neurons bristle with dendrites. And lots of dendrites in the hippocampus and the frontal lobe of your brain promotes, perhaps, the fluent flow of speech. Without estrogen, dendrites drop off neurons like the broken teeth of an old comb. Those left out of estrogen and low on dendrites may be left dazed and confused in the kitchen, wondering for what they came.
Back to our California rats. While physical activity increased their hippocampal BDNF, this exercise effect was reduced by a loss of estrogen in a time-dependent fashion. In other words, the longer the rats went without estrogen, the less brain benefits were derived from working out on the old exercise wheel. By the seventh estrogen-free week, exercise affected BDNF levels not at all. What's even worse, voluntary activity levels dropped off as well; those rats who were out of estrogen were disinclined to bustle about their cages for the sheer joy of mousy bustling.
Estrogen replacement then restored the rodents' BDNF back to normal levels. And hopping back on the workout wheel, in combination with long-term estrogen use, increased BDNF the most of all.
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