Rats! It's Welch's!

The average rat lives for 24 months. A 19 month old rat, therefore, is getting on in months and may well be on its way to becoming a doddering old rodent. In an effort to see if rats could retain their marbles well into their second year, investigators at Tufts University encouraged an aging rattine* group to exclusively drink Concord grape juice from the age of 19 to 21 months. One group knocked back a 50% concoction, another a 10% brew, and a confused final group got no grapes at all.

The half-strength gang excelled at motor skills (the team reported that this group of elderly daredevils were able to hang onto a wire for two seconds longer than all the rest -- suspended perhaps above a pen of hungry cats?). The ten-percenters, on the other hand, mastered a Morris water maze with an ease that shamed their thrashing colleagues, and then they oozed far more dopamine from their striatal slices -- this after they no longer needed their brains to stay afloat -- in a manner not usually seen in aging vermin.

The implications for those of us humans attempting to hang onto our aging brains but not necessarily wires? Dr. John Folts of the University of Wisconsin concludes that "a good antioxidant might be helpful" to old neurons. I don't know about you, but I've switched to Welch's as my a.m. juice du jour.
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*Just to prove you can find anything on the internet, check out the discussion on ratty adjectives at Ratty and rat rights.

Docosahexaenoic acid or DHA

DHA is an appealing PUFA (poly-unsaturated fatty acid) delivered by fish oil. French investigators theorize that this PUFA or omega-3 fatty acid becomes incorporated into the cell membranes of neurons. Once embedded in the cellular surface, DHA may protect against the injurious effects of beta-amyloid, the protein fragment that gums up the brainworks in Alzheimer's disease.

And in clinical news, a decade long study of Boston old fogies* showed a 48% decrease in the incidence of AD among those who had the highest levels of DHA from their regular intake of fatty fish.

Lead author, Tufts scientist Dr. Ernst Schaefer had this to say "These dramatic results show how older adults can play a significant role in their neurological health by increasing their intake of fish, fish oil or especially, DHA."
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*Arch Neurol. 2006 Nov;63(11):1545-50.

Silent brain infarctions

...and no air through the airway means no oxygen to the brain!

Clinically identified stroke represents the tip of the iceberg in terms of cerebral vascular disease by at least an order of magnitude...It is hard to believe, however, that loss of brain tissue should go without consequences. The brain may reorganize functional networks to adapt to lesions and recover function. But with each subsequent stroke, the capacity to do so is diminished.
--Brian J. Murray, MD

Silent brain infarctions or SBIs occur when a small amount of brain tissue is lost due to a lack of oxygenated blood to the area caused by a blockage in its blood supply. While any one such event can pass unnoticed, the cumulative damage from many such events builds up over time until the loss is manifested by neurological symptoms such as confusion or unsteadiness with walking. Nursing homes are filled with old ladies who lost their independence piecemeal in just such a fashion.

Scary new news on SBIs--one-fourth of persons with obstructive sleep apnea (the bedmate who keeps you awake as you lie awake waiting for him to take his next breath) were found in a Japanese study to have evidence of extensive silent strokes on MRI imaging.

How do you know if you've got sleep apnea if no one is lying awake waiting for you to breathe, and then telling you about it in the morning? Excessive daytime sleepiness,* a high red blood cell count, hypertension, and a short, thick neck are often associated with this dangerous condition.
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*As your oxygen levels drop off when you stop breathing, brain sensors rouse you to near consciousness to get you to make that big, annoying (to your bed partner) gasp for breath. While you may not be aware that you are waking up multiple times during the night, the lack of deep levels of sleep leaves you heavy-lidded by early afternoon.

Menopause morning

Moment, shmoment, this is turning into a day long lapse.

After looking frantically about for my cellphone, I called it to see if I could hear it ring somewhere in the house. No sooner did I hang up but the phone rang, my office manager calling to say the MIA phone was ringing on my office desk where I'd left it last night.

Then I rushed to exercise class, skidding into the lot at the last minute but, alas, no athletic shoes in the car. Between the moment I picked them up and the time I settled into the car, they vanished both from consciousness and arms.

When I arrived (late) to my dentist's office, I explained to his middle-aged receptionist the aggravating events of the day.

"Oh," she said in reference to the missing shoes, "I've done that. They're on your kitchen counter."

And so they were.

How can you tell if you've got memory problems?

Women who do too much classically suffer from CRS (can't remember you-know-what).

Overwhelmed and inattentive, we hurry with great purpose into the kitchen and arrive clueless as to why we're there. At what point, however, does distracted crossover to demented?

While people with age-associated memory deficits may have difficulty recalling names and retrieving information, their day-to-day functioning remains normal. Dr. Julie Fago of the Center for Aging at Dartmouth Medical School lists the following warning signs indicating when "brain freeze" may be progressing to Alzheimer's dementia.

* Inability to follow a complex train of thought, such as cooking a meal
* Trouble formulating problem-solving plans
* Difficulty finding the way in familiar places
* Increasing difficulty finding words or following conversations
* Increasing passive, unresponsive, irritable or suspicious behavior
* Misinterpretation of visual or auditory stimuli

So it's not a problem when patients forget they had an appointment with me (at least it's not a problem with respect to the long-term outlook for their brain). A cause for worry would be if they missed their follow-up visit because they couldn't find my office.

Apoptosis

Brain injuries, whether traumatic, toxic, or ischemic (lack of blood flow due to stroke or aneurysm), cause immediate cell death that is unavoidable. A secondary wave of death occurs, however, when cells adjacent to the damaged site basically commit molecular hari-kari. This secondary die-off is called apoptosis which means 'fading away,' an unfortunate event occurring in healthy neurons exposed to inflmmation.

Researchers have found in animal experiments that estrogen "dramatically" protects against this delayed cell death in brain injury. Neurobiologists at the University of Kentucky began the investigation by removing the ovaries of 100 rats, plummeting the unsuspecting rodents into menopause.

They then gave half the rats low doses of estrogen. After one week, the rats were subjected to an 'experimental stroke' as the researchers cut off blood flow through a cerebral artery. While estrogen did not protect against the initial cell death that occurred within hours of the stroke, it did markedly reduce the secondary damage.

Estrogen is known to have both direct and indirect benefits to brain cells. Scientists are working to develop 'non-feminizing' estrogens. In other words, such estrogen-like molecules would provide neurological benefits but would not occupy estrogen receptors in tissues like the breasts or uterine lining and, therefore, would not unfavorably stimulate these body parts in a cancer-causing sort of way.

Location, location, location

I gave my package addressed to Philadelphia, PA to the middle-aged clerk to weigh. She looked at the destination and smiled.

"I've been there," she said. "Alcatraz was fascinating."

That stopped me cold. Something not quite right about that statement.

"I loved the Golden Gate Bridge," she added.

Got it now. Right sights, wrong city.

"Oh, I think you mean San Francisco," I finally countered. She nodded in agreement and gestured to the package.

"I've been there too! Next I'd like to go to Niagara Falls."

That's in Florida, right?

Melatonin

Forget vitamins C and E. The unrecognized antioxidant hero of your molecular world may be melatonin. This hormone is produced by the pineal gland at the base of the brain particularly during the wee hours of the night. Melatonin levels are adversely affected both by light at night and aging, so if you're an aging insomniac, you should lie in bed and curse the darkness rather than light a single reading lamp.

Melatonin is a wonderfully efficient free radical scavenger. Free radicals are highly reactive oxygen- and nitrogen-based molecules in search of electrical stability. These unstable characters have such an immediate need for electrons that they will travel only an angstrom or two before exploding some important piece of your cellular machinery. The most effective antioxidant then is the one that's on site when these radical bad boys are produced.

Scientists call the area in which a toxic radical mutilates its neighbors the "reaction cage." Fat soluble vitamin E happily resides in the cell membrane, sopping up radicals in this reaction cage. Likewise, water soluble vitamin C works its magic in the water-based inner sea known as the cytosol. Not only does melatonin also work in these reaction cages, it is antioxidizing away in the mitochondria and the nucleus of the cell as well. In other words, melatonin is widely distributed throughout the cell, making it a scavenger extraordinaire, always in the right place at the right time.

Inexpensive, minimally toxic, and easily available in pure form (Consumer Labs tested 14 preparations and found them all to contain their advertised amounts of melatonin without contamination), melatonin has been lauded as a wonder treatment for the conditions that cause "feebleness in the elderly." In particular, melatonin prevents the secondary damage to brain cells caused by trauma, strokes, Alzheimer's disease, and Parkinsonism, effectively squashing the radical oxygen species produced as a result of these disorders.

If you've tried melatonin for sleep and found it wanting, consider coming back around on it in a higher dose, say 3 or 5 mg. This research suggests that you may want to take melatonin each night whether you need it to snooze or not.

Can't hold a thought. Period.

My forty-something patient and I chatted about her recent hysterectomy before we got started on the business of her annual exam. As we settled into her medical history, I ran through my usual questions about her energy level, sleep habits, diet, and exercise.

Moving on through the interview, I looked up and asked "So when was your last period?"

Estrogen and mood

Antidepressants are still first-line treatments for major depressive
disorder across the female life cycle, but when they fail, novel
approaches that integrate the use of estrogen are now being
investigated, including the use of estrogen by itself or in combination
with antidepressants.
--Dr. Stephen Stahl, UC San Diego

Investigators such as Dr. Stahl have an increasing appreciation of the many actions of estrogen on the brain. The same types of cellular receptors for estrogen that abound in reproductive tissues are also found throughout the brain, notably in many areas involved in mood and memory functions. Does your mind mind a lack of estrogen?

Dr. Stahl notes that phases of a woman's life associated with large hormonal fluctuations --think postpartum and perimenopausal-- are times in which a woman is at highest risk for the onset of major depression. Women with a history of a depressive episode following any estrogen shift are even more vulnerable to a recurrence following other 'reproductive events' later in life. In other words, if you think premenstrual was difficult, look out for perimenopause.

Stahl calls this phenomenon 'kindling,' and theorizes that each mood crash associated with estrogen withdrawal may actually damage the brain. He dubs this process excitotoxicity in which the neurons are literally excited to death, and these episodes increase the future risk of treatment-resistant depression under similar hormonal circumstances.

A study supporting the use of estrogen in the treatment of depression was conducted at Massachusetts General Hospital. Fifty perimenopausal women --defined here as the transitional state from cycling hormones to no hormones at all marked by irregular periods and elevated FSH levels-- were diagnosed with varying degrees of depression. Half were randomized by investigators to receive estradiol (known to some as 'bio-identical' estrogen) via a skin patch such as Vivelle Dot or Estraderm. The control subjects got sticky, hormone-free blanks.

Two-thirds of the estradiol treatment group were depression free after three months of patchwork compared to only one-fifth of those without hormones.

Is frustration frying your brain?

When your teenager awakens in the morning with a fully developed case of rage, do you go there with him, or do you smile benignly at the little darling and turn the other cheek? A study out of Maryland* suggests that your response may significantly influence your risk for a stroke.

I'll bet these Baltimore investigators had a field day with this one. They invited 67 "older subjects" down to the lab for an afternoon of testing. The unsuspecting seniors (ages 55 to 81) were subjected to "repeated interruptions of statements and harassment during mental arithmetic tests," while their vital signs were monitored as the aggravation wore on.

The hot reactors in the group raised their blood pressures along with their ire. These simmering subjects were found to have a significantly increased number of unsuspected little infarcts on subsequent MRI brain scanning (see 'The White Matter Matter' below). In other words, their explosive reactions to life's little unpleasantries had taken a permanent toll on the health of their brains.

Lead investigator Dr. Shari Waldstein concluded, "If these findings are replicated, it may be worthwhile to investigate whether treatment of stress-induced blood pressure responses -- in addition to the resting blood pressure -- can reduce cerebrovascular risk."
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*Waldstein, SR, et al. Stroke. 2004 Jun;35(6):1294-8.

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.

The white matter matter

The brain is divided into two main regions: the superficial gray matter, and the white matter below. Gray matter is the surface control center; the nerve cell bodies in this layer connect to one another via long extensions called axons. These electrical connectors travel through the white matter, so-named because a white, fatty material called myelin surrounds and insulates the axons, one from another.

We have long known that damage to the gray area through stroke or injury results in devastating paralysis and loss of physical functions such as speech. Through the fancy radiological technique of magnetic resonance imaging (MRI), we now know that the white matter is also vulnerable to a patchy sort of damage which, over time, can have a cumulative effect on motor, speech, and thinking skills.

These damaged areas appear on MRI scanning as small bright spots within the large body of white matter. The number of these 'white matter hyperintensities' (WMH) increases with age. WMHs have also been linked to a history of hypertension, migraine, and depression. Microscopic studies done on brains whose owners no longer need them confirm that these areas represent ischemic damage due to a loss of blood supply and fresh oxygen to the tissue. Many bright spots in the brain do not foreshadow a bright future for cognitive functioning. The following two studies have aided researchers in understanding the significance of such MRI findings.

Maryland researchers at Johns Hopkins University scanned the aging brains of 3600 individuals and graded the white matter abnormalities from 0 (no white matter matters to speak of) to 9 (a huge load of stressed-out white matter). Over the next five years, they followed the group for the occurrence of stroke. The higher the grade, the more the brains failed to age in good style. Those whose white matter was heavily spotted and bright (grade 5 or higher) had triple the stroke incidence compared to those whose white matter was scarcely spotted at all.

In 1932, public health authorities in Scotland administered the "Scottish Mental Survey" to all the resident 11 year olds. In 1999, scientists at the University of Edinburgh rounded up a bevy of 78 year olds and compared their current cognitive ability to their pre-teen mental testing as well as their current brain MRI scans.* The scientists found that the amount of white-matter lesions in their subjects' aging Scottish noggins was a better marker for present mental functioning than the early-age IQ scores. Furthermore, the impact of the white matter changes was independent of youthful mental ability.

Don't take it's 'just age' for an answer if bright spots are spotted on your MRI scan. Get cardiovascular risk factors such as elevated blood pressure, cigarette use, elevated blood sugar, and high cholesterol out of your life.
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*Leaper, SA et al. Radiology. 2001 Oct;221(1):51-5.Click here to read

Just plane trouble

I was standing in the crowded aisle of the plane, waiting for the attendants to unlock the doors and let us out. I realized, with a sudden weak-in-the-knees, adrenalin sort of rush that I did not have my purse with me. Hoping to find it stowed on the floor of my seat, now several rows back, I turned to face the crush of people pressing forward.

"Scuse me...so sorry... left my purse...pardon me."

I squeezed my way against the crowd, arms held tightly against my chest. Finally, I reached my former seat and leaned forward to check the floor for my purse. Freed at last from my tight grip, it swung forward from my shoulder to hit me in the face. My very red face.