Tablet rasa

Me: What supplements do you take?
Middle-aged woman: Glucosamine...B...er...E...oh yeah D...fish oil...ginkgo...and...um...ohh that other C one.
Me: Do you mean vitamin C?
MAW: (laughing) Yes, that's it!
Me: The gingko's not working.

Hare to hair!

I was shuffling down a leaf-covered sidewalk, enjoying the late afternoon sunshine. The lady of the house was out front raking, her mid-sized mutt clamoring at her heels for a game of fetch. Spying me, he grabbed his small toy, a saliva-soaked bunny, and dropped it at my feet. He was used to the well-aimed flick of an expert wrist, so he raced down the block anticipating the toss. I, in turn, heaved the soggy animal and hit his mistress upside her head.

A neighborly piece of advice?

Five words you do not want to hear from your son while you're out of town whether you're menopausal or not:

Did the neighbors call you?

Baked and befuddled on the Boulevard

I went to a lot of trouble to cross midday traffic on Colorado Blvd. to get to The Great Harvest Bread Company. Cute little bread girl pierced like a pin cushion gives me huge slab of 9-grain bread with butter to eat while I'm waiting for my loaf to go through the slicer. I pay up, leave with bread in hand, savoring my good luck and the fact that I will have something to munch on as I crawl home through northbound traffic.

After slogging through two blocks of brake lights, I start thinking about bread in hand vs. bread in bag...sliced...sitting undisturbed on the Bread Company counter. Beskewered bread girl does not offer me a second slice of bread, nor does she find my "Oops, menopause moment!" comment the least bit funny.

Whose moment was this?

My patient and I chatted as I did her Pap test. I always try to carry on a bit of light conversation during this uncomfortable task.

I withdrew the brush, trying, as always, to do so without knocking the tip into the speculum. Who knows what happened next, but the flexible plastic handle bent like a bow, sprung from my fingers. flew through the air like an arrow then bounced off of the wall and onto the floor.

My patient did not miss a beat but continued her story about her college-age son. Could she really not have noticed the brush as it circled above her and landed on the floor next to the exam table? Barely suppressing my urge to burst out laughing, I fumbled for a new brush and repeated the sampling. If my patient was aware of my antics, she was too polite to say.

Making medical decisions in menopause: A workshop

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.

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:

• 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

In other words, the person is bothered by memory troubles and, while other people have noticed the deficit, the subject's daily life is unaffected by mental deficits. I start to worry when I hear about troubles in job performance, difficulties with multi-step tasks that were not formerly a problem, frequent missed obligations, and an inability to learn new information. I am especially concerned when the kids call or come in with mom to discuss this issue, and--worst of all--when others are concerned but the patient is not.

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.
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(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.

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!
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(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.

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.
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*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.

The changing face of primary care

My medical partner and I are facing big changes in the way we deliver medical care. I urge all of you--particularly my patients--to head over to Denver Doc Online and read about our dilemma, then leave your thoughts behind.

What's your read on this?

I noticed this a.m. that all three pairs of readers were on the kitchen table. Oh-oh, I thought, that may spell trouble later on. But I didn't do anything about it, and now I can't find a single pair.