Window of Opportunity of Estrogen Therapy for Neuroprotection

Those of you who find this topic one of interest should check out the newest post at my other blog: Menopausemoments.blogspot.com.

Social genomics and loneliness

The term social genomics is a new one to me. The fact that social factors influence health is not.

I wrote some time ago about the effects of self-described loneliness/social isolation has on the health of older adults. UCLA researchers examined the white cells of persons who were highest of the "high-lonely" vs. those "low-lonely" (socially connected) subjects.(1) A total of 209 genes showed different levels of expression between the two groups. Over 4 years of study, the lonely crowd over-expressed genes that resulted in inflammation and under-expressed those involved in antibody production against bacteria and viruses.

These DNA effects of social isolation were very specific to three groups of genes. The first group of affected genes are involved in the early phase of the immune response wherein the body revs up inflammation as a first response to injury or infection. I have written numerous times about the blessing/curse of inflammation insofar as appropriate levels are essential to a successful recovery from infection but too much (think cytokine storm in influenza pneumonia) or wrong place at the wrong time (say in an arterial wall that has cholesterol build-up) can be counter-productive or downright destructive.

The other two groups of immune genes that respond to the lonely soul's transformed internal environment are those that stimulate the production of interferon (a molecule that amplifies immune response against viruses) by lymphocytes and those that stimulate production of antibodies by B lymphocytes. The activity of both these types of genes is diminished in people who are less connected to friends and family.

The psychological literature abounds with studies in which socialization is correlated with susceptibility to viral illness. In another one of those 'who the heck volunteers for these things' type of study, researchers at Carnegie Mellon University assessed 193 subjects for PES (positive emotional style) vs. NES (negative emotional style of course) and then sprayed rhinoviruses/ common cold or influenza viruses up their noses to see who got sick.(2) Those NES-positive individuals, described as anxious, hostile, and depressed were 3 times as likely to succumb to the influx of nasal virus compared to all the PES prone Pollyanna types who were happy, lively, and calm.

Per Steve Cole, co-author of the study on white cells and loneliness: Research in social genomics has now clearly established that our interpersonal world exerts biologically significant effects on the molecular composition of the human body.(3) What remains to be seen is how attitude adjustments of the cognitive or pharmocological variety can affect how our DNA gets activated.
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1) Cole SW, et al. Social Regulation of Gene Expression in Human Leukocytes. Genome Biol. 2007;8(9):R189.
2) Cohen S, et al.Positive emotional style predicts resistance to illness after experimental exposure to rhinovirus or influenza a virus.Psychosom. Med. 2006 Nov-Dec;68(6):809-15. Epub 2006 Nov 13.
3) Cole SW. Social Regulation of Human Gene Expression. Current Dir. In Psych. Sci. 2009 Vol 18 No 3.

Is Multitasking Bad for Your Brain?

This morning I was perusing an August issue of Science. My husband walked into the kitchen and switched the radio on to NPR's Car Guys, then began grousing about what idiots they were and what bad advice they gave. So there I am, reading, drinking coffee (I don't suppose that counts), listening to those Car Guys yuk it up, and degrousing the spouse (that's what you do when you acknowledge someone's rants with sympathetic murmurings of assent). Oddly enough, in one of those 'bloggable moments' that those of you who blog know so well, the magazine article I was reading was "Multitasking--Bad for the Brain?"(1).

A word or two first about multitasking--I don't know when the word was coined, but in this day and age of electronic devices, the skill ranks right up there with missing sleep to multitask as one of the characteristics of New Age success. The ability to text, talk on the phone, work on the computer, and troubleshoot simultaneously is the mark of a modern manager (and that, Jean C, is why we pay you the big bucks!). More than once I've cited 'inability to multitask' as one of the job requirements that a patient applying for disability can no longer perform.

I personally go into what I call overwhelm mode if called on to multitask too long. Bi-tasking I can do, fielding an urgent message say in the middle of an exam, or mixing pancake batter while talking on the phone. Well actually, the latter has proven problematic in the past. But layering calls from the ER, prescriptions, annual exams, work-ins, and a kid crisis in a single afternoon puts me over the top with agitation.

So here's what Stanford scientists found when they compared 19 heavy habitual media multitaskers with 22 persons who generally limit their electronic input. The subjects were tested for their ability to filter out irrelevant environmental information as well as "irrelevant representations in memory." In addition, all the volunteers were also tested for the ease with which they switched tasks. Those heavy duty multitaskers (IM'ing, skyping, texting, gum-chewing fools no doubt) were more distractible and less able to switch tasks midstreams than their colleagues who characteristically uni- or bi-tasked.

The obvious question that arises from this study: Do multitaskers scramble their brains in the multitasking or are they just a flighty, distractible bunch from the get-go who are attracted by nature to a 3-ring cognitive circus?

My reaction to my a.m. over-stimulus? I excused myself ASAP to go blog, taking my IPhone along so I could respond to a text that just came through from Jean C.
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(1) Ophir, E, et al. "Cognitive Control in Media Multitaskers." Proc Natl Acad Sci USA. 2009 Aug 24.

Verbal fluency exercises

Verbal fluency or the ability to find the right word at the right time in a timely fashion is one of those front brain skills that lags with age. Add dwindling hormone levels, social isolation, and/or a history of even a mild concussion, and you may end up as fumble-mouthed as an evening news anchor.

We know that reading, working crossword puzzles, and interacting with friends are all ways to support brain function and verbal fluency. To heck with all that, how 'bout still another way to waste time on the Internet? Try lumosity.com, a web-site full of games that do both--bolster your brain and while away time you don't have. In particular, have a go at Word Bubbles which not only tests your verbal fluency but your typing and spelling skills as well.

And thanks, or no thanks, to my niece Miranda for the loss of many an hour!

The oriented-in-space place

Drawing a mental blank is a drawback of a busy day; being unable to draw a mental map of your current location is a red flag for trouble. While getting lost in your work rates high performance reviews, getting lost while driving maybe a sign of dementia.

Arriving safely at home at the end of our day requires the proper functioning of an oriented-in-space place in our brains located just behind and above the ear. This medial superior temporal area (MST) is charged with personal global positioning, providing our brain with continual updates on our current location in space.

Unfortunately, the MST is particularly vulnerable to the cellular destruction associated with Alzheimer's Disease(AD), leaving its victims unstuck in their once familiar world. This deficit has been dubbed 'motion blindness'; the the resultant inability to navigate, even through one's own home, leads to a tragic loss of independence.

Here's another scary consequence. While early AD victims may remember street names and the basic rules of the road, there are certain driving skills that lapse early in the course of the disease based on MST dysfunction. I remember an office visit where my elderly patient arrived slightly late for her appointment. She sat down in the chair with a sigh, then proceeded to recount her harrowing drive over during which, per her report, she sideswiped several cars on both sides of the narrow streets near my office while trying to guide her car down the middle of the road. She had no sense at all of where her car ended relative to those parked by the curb.

I don't know what was more disturbing--her zigzag navigation of a potentially lethal weapon or her relative indifference to destruction that she left in her path.

Of linens and proteins...*

And stressful situations in closets and cells.

I've mentioned before that I suffer a weensy bit from disposophobia or the inability to part ways with stuff. Old towels are no exception. My linen closet bulged (past tense due to recent reform efforts) with tattered towels and sheets too short for current mattresses. As I dug deeper in search of bath accessories with the most residual fluff, the rifled remaining towels took up more and more space, threatening the hinges on the closet doors. I desperately needed an unfolded towel response (UTR).

Enter the towel-like equivalent of body clutter, namely unfolded proteins. Not only do your cells need to string the appropriate sequence of amino acids together to form proteins, but they also must pull a little proteinaceous origami trick to get them into the right spatial configuration for proper functioning. Unfolded proteins are the bane of an aging cell's existence--witness all that rumpled beta-amyloid protein that gums up old neurons in Alzheimer's disease.

Hurrah for evolution! Enter the unfolded protein response (UPR), nature's way of sensing a haphazard pile of proteins on the cellular floor. And if the UPR can't straighten up the protein closet--wadded proteins stacking ever higher--then the UPR just makes some sort of nasty enzyme that explodes that cell and its proteiny mess right then and there.

Alas, as Dr. Dale Bredesen of the Buck Institute for Age Research points out, the UPR is no different than a lot of other body responses to dysequilibrium: "The initial response is protective, but the late response is destructive." He and other neurobiologists are hoping to unlock the secrets of UPR in order to keep this organizing principle on our side.
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*Check out Menopause Moments for a review of a book with one theory how misfolded proteins may be the infectious basis for Alzheimer's Disease.

Fretful and friendless raises risk of dementia

Just untangling the conclusions of this Swedish study was a brain workout in its own right, a downright 'how much wood would a woodchuck chuck..." sort of puzzle:

Neither high neuroticism nor low extraversion alone was related to significantly higher incidence of dementia. However, among people with an inactive or socially isolated lifestyle, low neuroticism was associated with a decreased dementia risk (hazard ratio [HR] = 0.51, 95% confidence interval [CI] = 0.27-0.96). When compared to persons with high neuroticism and high extraversion, a decreased risk of dementia was detected in individuals with low neuroticism and high extraversion (HR = 0.51, 95% CI = 0.28-0.94), but not among persons with low neuroticism and low extraversion (HR = 0.95, 95% CI = 0.57-1.60), nor high neuroticism and low extraversion (HR = 0.97 95% CI = 0.57-1.65).(1)

Got it? So do we fret and socialize, stay home and calmly knit, or placidly go out drinking with our buddies? Don't freak out while you discuss this conundrum with your friends because, as you will see once you sort out the various possibilities here, being a Buddha of a buddy is your best bet for the brightest brain.
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Wang, HX, et al. Personality and lifestyle in relation to dementia incidence. Neurology. 2009 Jan 20;72(3):253-9.

How do crossword puzzles help my brain?

Check it out at Menopause Moments.

Can NSAIDs prevent Alzheimer's Disease?

Alzheimer's disease (AD) gums up the brainworks with tangled neurons and protein plaques. Much of the damage occurs, however, as a result of an inflammatory response to these changes. Scientists theorized that the regular use of anti-inflammatory drugs such as Advil, naproxen, or Celebrex (also known as non-steroidal inflammatory drugs or NSAIDs) could slow down or prevent this degenerative disease.

The Alzheimer's Disease Anti-inflammatory Prevention Trial(1) enrolled over 2,000 seniors aged 70 years and older and followed them through 7 years of life correlating the use of NSAIDs (naproxen 220 mg. twice daily, Celebrex 200 mg. twice daily, or a look-alike placebo with no anti-inflammatory properties at all). All participants had a family history of AD and were thus considered to be at increased risk for developing the disease.

Made no difference what the septuagenerarian subjects took--naproxen, Celebrex, or no drug at all--with respect to their subsequent tendency to drift towards dementia. In fact, there was 'weak evidence' for a detrimental effect of naproxen.

The problem, however, is that this really wasn't a preventive trial at all. By the time old folks enter their eighth decade, they may well already be on the road to AD. Chemopreventive studies--i.e. those research trials seeking substances that actually protect against the development of AD through a neuroprotective substance-- would need to be undertaken on younger subjects over a longer period of study, an approach that is prohibitively expensive. The studies that suggest that NSAIDs are indeed useful in AD prevention are largely observational and/or retrospective; large populations are quizzed as to their health habits and medication usage, and these reports are correlated with present or future health outcomes. And if you've ever quizzed an old person about their drug use now and in the past, you may well wonder as do I how accurate those self-reports really are.

While the jury's still out as to whether NSAIDs are useful against AD, there is evidence that they may lower the incidence of cancer, and they certainly are good for pain. On the other hand, a recent study(2) showed a strong link between their use in patients also on anti-depressants such as Prozac or Lexapro (aka SSRIs) and gastrointestinal bleeding. Those on this pharmaceutical duet were 4.8 times more likely to bleed from their upper GI tract.
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1. ADAPT Research Group. Cognitive Function Over Time in the ADAPT: Results of a Randomized, Controlled Trial of Naproxen and Celecoxib. Arch of Neur. 2008;65(7): 896-905.
2. deAbajo FJ, et al. Risk of upper GI tract bleeding associated with SSRI and Venlafaxine therapy: Interaction with NSAIDs and effect of Acid-suppressing agents. Arch of General Psychiatry. 2008;65(7):795-803.

Working memory and menopause moments

Wondering why you're wandering around the house in pursuit of who can remember what? Check out Working memory and menopause moments.

Panic attacks and menopausal women

The first time I had a panic attack, I assumed that my heart rhythm was abnormal, and that was why I felt like I would lose consciousness as I drove to Boulder. By the second panic attack, my educated guess was that a tumor was pressing on my trachea, and that was why I could not draw a deep breath and might have a seizure at the wheel. Needless to say, driving after my snowy day collision with a moving van became a bit of an ordeal. As a result of my experience, I know that panic attacks are not about an anxious fear that you might die but rather a strong bodily feeling that you will die.

I was interested, therefore, to read a study in last year's Archives of General Psychiatry about cardiovascular outcomes in postmenopausal women who suffer from panic attacks. Panic attacks are common among women in this age group (although mine occurred over a decade ago). Researchers collected data from nearly 3400 women who participated in the Women's Health Initiative Observational Study.* The women self-reported whether or not they'd experienced panic attacks over a 6-month period, then they were followed for the occurence of coronary heart disease (CHD), stroke, or death in the next 5 years.

A 6-month history of full-blown, real deal, I-can't-get-a-deep-breath or I'm-going-to-die sort of panic attacks was significantly correlated with both outcomes in a scary sort of way. The women demonstrated a 4.2 fold increased risk for CHD, a 3.08 increased risk for the combined outcome of CHD or stroke, and (yikes!) a 1.75 times increased risk that those subjects who ducked heart attack or stroke would die of any other thing.

No surprise, panic attacks are awful, and they simply are not good for you.
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*Participants in the WHIOS were those women who either were not eligible for the hormone portions of the WHI but agreed to provide investigators with other information about their lifestyles and health outcomes. This particular sub-study was the Myocardial Ischemia and Migrained Study.

Overactive bladders

This posting is not really about twitchy aging bladders that can't hold their own against a simple cup of coffee without whining uncomfortably for attention, but rather about the effect those frequent signals to head for the head have on our already addled brains.

Here's how the bladder connects with brain. That 'gotta' go now' message is sent to Barrington's nucleus, the brain center in charge of bladder contraction and urination. But no simple reflex here; rather than just send back a simple command to let 'er rip or hold on a moment dear, Barrington's nucleus feels compelled to tell the locus ceruleus all about it. This is the area in our noggin in charge of arousal and attention. I guess it makes sense because someone's got get up, find the loo, and transport the bladder there to do its business.

So researchers in Pennsylvania asked a group of rats to participate in an experiment wherein their bladder outlets were surgically narrowed to mimic an obstructed or overactive bladder(1). While Barrington's nucleus showed decreasing activity in the obstructed rodents compared to a control group (which may explain why people with OAB leak without knowing it until it's too late), the obstructed group demonstrated a hyperactive locus ceruleus.

Because the locus ceruleus is connected to the cerebral cortex, an area in charge of thinking, mood, and memory, the Philadelphia investigators conjectured that this hyped up bladder thing ultimately could affect behavior in an adverse sort of way. Indeed, the poor blocked-up rats brain activity consistent with chronic hyperarousal as seen in persons feeling anxious or stressed. And when the rats with obstructed bladders slept, their brain activity showed theta waves associated with restless sleep.

Researchers concluded: "Overactive bladder as a result of partial obstruction is particularly prevalent in the elderly, a population that is also vulnerable to neurobehavioral deficits and sleep disturbances. The present findings suggest that this visceral dysfunction may contribute to neurobehavioral and sleep deficits in this population."

Of course, surgically obstructed male rats are one thing, and aging women with overactive bladders quite another, but OAB may be just another brick in the deteriorating wall of our aging brains.
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(1)Rickenbacher, E. et al. Impact of overactive bladder on the brain: Central sequelae of a visceral pathology. Proc Natl Acad Sci U S A. 2008 Jul 21. [Epub ahead of print]

Enduring love or just never letting go?

When it is our time to grieve, we must live each day as it comes,
dealing with both the mundane routine of living and our inner struggle.
Grieving and living through the entire experience of bereavement will
change us, and if we do it well, the change will be for the better. We
know we are becoming whole when we can look to the future with some
readiness to engage once more.
--Carolyn Jaffe "All Kinds of Love: Experiencing Hospice"

Grief, of course, has been a part of my life and thoughts this past year, both during the final months of my mother's life and the time since she died in late March. I have been surprised at the ease with which I've made this transition since her death, realizing though that she and I had ample time to say good-bye and knowing that she was ready to exit when she did. Interesting research from UCLA(1) suggests that those who experience what is termed 'complicated grief'--defined as feelings of loss that are so overwhelming that the person is debilitated and unable to resume normal life--have characteristic patterns of brain function underlying this show-stopping state of mind.

Psychologists there studied a group of women who'd experienced the loss of a mother or sister in the previous five years. The subjects were classified as either complicated or noncomplicated grievers. Using functional MRI imaging (fMRI), a technique that can identify which parts of the brain are actively at work, the researchers found that all the women lit up their pain centers when they viewed either pictures of their loved ones or words related to loss. Neutral words or pictures of strangers did not elicit this response.

They were surprised, however, to discover that those women suffering from ongoing complicated grief also activated the nucleus accumbens area of the brain. This region is the neurological command center for experiences of pleasure and reward. While it is unclear why this occurred, lead researcher Dr. Mary-Frances O'Connor theorized that intense attachment in complicated grief activates reward centers in ways similar to that experienced by contact with the loved one before death occurred. Those with fMRIs lit up in reward centers all reported 'yearning' but there was no correlation with the time that had passed since the death.
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O'Connor, MF, Craving love? Enduring grief activates brain's reward center. Neuroimage 2008 May 10. [Epub ahead of print]

Sleep apnea and memory problems

You snooze, you lose. Neurons, that is, in charge of memory function, lost when you go apneic (quit breathing) while sleeping. Check out the details at Menopause moments.

Methylfolate and depression

...or how to B undepressed.

Folate is a B vitamin that occurs naturally in green leafy vegetables. It plays a host of important roles in the human body, and is so essential to the proper construction of the nervous system of a developing human that the FDA mandated in 1996 that its synthetic form--folic acid--be added to breads, flours, and other grain foods.

The trouble with folic acid supplementation or even naturally occurring dihydrofolate from food sources is that the body must convert them into the active form which is L-methylfolate (known as MTHF--yes, I thought of that word too the first time I read it). Some people are better MTHF producers than others. For purposes of our discussion, we will focus on the effects of MTHF deficiency and the fully developed brain.

The brain is tightly guarded by the 'blood-brain barrier.' Certain molecules can't pass through the blood vessel walls into brain tissue, and folate is one of them. MTHF, on the other hand, slips right in, and a right good thing it does because it is an important co-factor in producing the three most important neurotransmitters involved in mood regulation. If you're low on MTHF, studies suggest that you may subsequently run low on dopamine, norepinephrine, and serotonin. We're talking transmitters with a capital T that rhymes with D that stands for depression.

A host of research shows that supplementing methylfolate--thus skipping the necessary internal steps to activate folic acid--improves depression under a host of circumstances. This being an older person's health blog, let me illustrate with one study which supplied sad, old people with MTHF.

Researchers coaxed 20 elderly people who were not only Italian but also depressed to take 50 mg daily of MTHF rather than antidepressants. Four said the Italian equivalent of 'what's the use' and quit. The remaining subjects showed significant improvement in their depressive symptoms.

But you don't have to be old to enjoy the potential mood elevation of MTHF. A product called Deplin is now available by prescription and specifically indicated for use in patients having a less than stellar response to antidepressants. Theoretically, it might also be useful for persons with mild mood disorders not on other medications.

The basic science literature supporting the theory that MTHF improves brain function is large, but clinical research, except for the random Italian or so, is sketchy. Thus Deplin has been designated a 'medical food' which apparently does not have the stringent proof requirements of prescription drugs. Nevertheless, no adverse effects of MTHF supplementation have occurred, and a downloadable coupon at deplin.com makes this an affordable gamble of a therapy.

I cry too much...

(or Better Mourning through Chemistry)

I cry easily and often. Certainly over the morning comics--who doesn't? For Better or Worse and Funky Winkerbean rival any soap opera or Greek tragedy for tear jerk potential. I cry when small children sing more or less in unison, I cry when other people cry, and, most distressingly, I cry when I'm mad.

Now don't get me wrong, there's nothing wrong with crying (cut to "It's alright to cry" from Marlo Thomas's "Free to Be You and Me" album which, incidentally, is a song that also makes me cry). But sometimes, crying gets in the way of effectively doing that which you want to do. Years ago, I wrote a eulogy for my Dad's memorial service, and I couldn't get through one word of it due to tears so my good friend Janice read it for me.

Last week, I threw a marvelous memorial service for my Mom, complete with a sing-along hootenanny of old favorites like "Down in the Valley" and "You are My Sunshine." I wanted to sing along and, more than anything, I wanted to speak my good-bye piece to Mom and tell her friends about the wonderful times she and I shared even up until the last week of her life.

Prior to the service, I took a little bit of Paxil (an older antidepressant/anti-anxiety drug) and a little bit of propranolol (a beta-blocker that stops some of the adrenalin outflow from the sympathethic nervous system that sets off the heart-pounding, shaky body feeling like when you battle a saber-toothed tiger or say good-bye to your mother). I wasn't tranquilized, I was still awash in emotion, but I was NOT awash in tears. I sang my songs (and I am not generally one to sing in front of a crowd) and I said my piece. It was wonderful.

I cried like mad the next day.

Baby boomers and Alzheimer's Disease

Here's hot-off-the-press bad news for baby boomers: 1 in 8 will develop Alzheimers' Disease. Lifetime risk for those of us BBs who are, have been, or will be 55 is 17% for women and 9% for men.

Women are more vulnerable to AD due to gender susceptibility and longevity. While men tend to die earlier and more abruptly, women tend to dwindle piecemeal with degenerative disease.
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*2008 Alzheimer's Disease Facts and Figures

HDL cholesterol supports the brain too

HDL cholesterol may slow the aging process, and not just with respect to the heart. The worthy little HDL protein plays a pivotal role in reverse cholesterol transport, toting the fatty goo out of the tissues--including blood vessel walls--and back to the liver for elimination from the body. Low levels are a common abnormality in patients destined to develop coronary artery disease, even when total cholesterol values are in the normal range. Researchers have now found a correlation between robust HDL levels and mental clarity in the oldest of the old.

Scientists at the Institute for Aging Research in New York City conducted a study of healthy, really old people (average age 99). They found that these remarkable centenarians maintained much higher HDL levels than expected for their age. HDL levels decline with the passage of time by approximately 5 points for every 8 years. According to this formula, the expected HDL level in this gasp of geezers should've been 20 but averaged 55.

Across the study group, HDL levels were directly related to scores on the Mini-Mental State Examination. The higher the HDL's, the more agile the aging brain. Investigators note that cholesterol plays a key role in maintaining connections between brain cells and processing beta amyloid protein, the tenacious gunk that gums up the neural works in Alzheimer's disease.

Postural perseveration

Necessity is the mother of invention...necessity is the mother of invention...necessity is the mother of invention...
--My Mom

There are days that my Mom doesn't know who I am, and days where she can't even talk. Today she was firing most neurons in a satisfying way. We talked over coffee on a wide variety of subjects--why her oxygen level is low, what is diffusing capacity, how cooking freed pre-humans to develop large and energy intensive brains, how our human genome fosters obesity and diabetes through overeating, etc. In short, the first hour of our visit was a remarkable conversation with Mom as she used to be.

As we rolled to the dining room, however, the situation changed. She'd now been up an hour, and fresh blood to brain was starting to slow. Towards the end of our free flowing talk, she'd wondered if inventors were generally poor as the lack of resources available in poverty might make them more resourceful. "Necessity," I reminded her, "is the mother of invention."

She proceeded to repeat that old adage, first in a thoughtful, musing sort of way, then in an increasingly broken record sort of automatic repetition. Pure perseveration this--an uncontrolled repetition of a word or phrase, and a sure sign the brain is slipping its gears. In short, she was having another postural TIA.

"Oh Jude," she finally gasped, "How do I turn this off?" She became too agitated to eat. I took her back to her room and helped her into bed. As is often the case when gravity robs her brain of blood flow, she was scarcely able to move her left leg to negotiate the three steps from wheelchair to bed. I should've known better, an hour of talk is too much of a good thing.

Verbal fluency

Verbal fluency (VF) is defined as the ease with which a person can find the right word and use it at the right time. Verbal fluency tests generally involve a timed interval in which a person is asked to name as many animals (fruits, vegetables, words that start with Q, etc) as they can during that time.

I test my verbal fluency every day in the consultation room as I explain this, that, or the other medical condition to a patient with more or less ease. Progesterone definitely slows down my VF as does a lack of estrogen. Progesterone is known to have sedating effects on the brain, and my frontal lobe is clearly affected by my periodic use of Prometrium, a proprietary formulation of natural progesterone. A dose at bedtime gives me a great, dream-filled sleep but leaves me fumble-mouthed on the job the following day.

Likewise, estrogen has a strong influence on verbal memory, and some of my patients who choose to motor into menopause without HRT find their word-finding abilities seriously impaired. Estrogen supports the function of cholinergic neurons in the brain (those brain cells that communicate one to another via a neurotransmitter called acetylcholine). Cells in charge of verbal memory and executive functioning are cholinergic neurons and thus affected by lack of estrogen. Likewise, anticholinergic medication such as antihistamines (which are used as over-the-counter sleep aids) also can leave the user tongue-tied with respect to VF.

Not only does dementia cause decrease in verbal fluency, so often do head injuries (as the frontal lobe sitting just behind the forehead, is often first to hit the windshield in accidents), Parkinson's disease, schizophrenia, diabetes, and alcoholism. Persons with chronic lung disease are known to have cognitive troubles whether or not they're running short on oxygen levels. Ohio investigators found that 20 minute exercise sessions significantly increased verbal fluency scores on patients with COPD.