Everything is Shrinking, Including My Brain.

First it was the automobiles.  They get smaller and smaller.  Then computers, cell phones, etc.  Has anyone out there besides me gotten totally frustrated trying to text on those tiny keys????  Then the NEWSPAPER.  It is like the size of a birthday card now!  The newest and most disturbing trend is GIRL SCOUT COOKIES.  They are virtually HALF the size they used to be.  And not half the price, alas.  At some point they will be about the diameter of a quarter.  And cost more than they do now, to be sure.  What kind of planet do we live on anyway?  One where things constantly get smaller, evidently.

Even my brain is shrinking.  And I can tell.  I thought at first it was due to stress and depression.  You see, that's been proven.  I turned up some interesting proof on the Psychology Today website to confirm my worst fears. A new research study has uncovered the genetic mechanism underlying these brain changes.  You see, depressed brains are more fragmented.  I KNEW my brain needed defragmenting, just like my hard drive, the size of which, is also diminishing.  We have an external hard-drive now that is the size of a deck of cards, although don't be impressed; I am fairly sure there is one now that is the size of a matchbox...But I digress.  In the study, conducted by Professor Richard Dumin and colleagues from Yale University, scientists compared the genetic makeup of donated brain tissue from deceased humans with and without major depression. (NOW I know what I can do with my brain when I am finished with it....) Only the depressed patients’ brain tissues showed activation of a particular genetic transcription factor, or “switch.” Scientists hypothesized that in the depressed patients’ brains, prolonged stress exposure led to disruption (due to this switch) of brain systems involved in thinking and feeling. Depressed brains appeared to have more limited and fragmented information processing abilities. This finding may explain the pattern of repetitive negative thinking that depressed people exhibit. (It explains A LOT more than that.) It is as if their brains get stuck in a negative groove of self-criticism and pessimism. They are unable to envision more positive outcomes or more compassionate interpretations of their actions.  

As for stress, things called glucocorticoids, or stress hormones, damage brain neurons.   The stress response activates a brain region known as the amygdala, which sends a signal alerting the organism (you) to the threat, releasing short-term hormones like cortisol which prepare the organism (again, you) to sustain “fight or flight” and fend off an attacker. But with long-term exposure from stress that is not life-threatening, these hormones appear to cause brain neurons to shrink and interfere with their ability to send and receive information. In animal studies, under chronically stressful conditions, glucocorticoids such as cortisol can remain elevated for long periods afterwards.  And any middle-aged woman out there also knows that cortisol makes you fat around your middle. Nice little bonus there. 

Research in both mice and humans has demonstrated an association between stress exposure (footshock in mice, life events in humans) and shrinking of the hippocampus – the brain center responsible for forming new, time-sequenced memories. Studies done of sufferers of PTSD have shown this to be true.  In another study, patients recovered from long-term major depression showed a 15% decrease in volume of the hippocampus, compared to non-depressed patients.

Major life stress probably also shrinks brain neurons in the Prefrontal Cortex (PFC), the brain area responsible for problem-solving, adaptation to challenge, emotional processing and regulation, impulse control, and regulation of glucose and insulin metabolism. In a studty of 100 healthy participants conducted by Dr Rajita Sinha and colleagues at Yale University, and published in the journal Biological Psychiatry, those with more adverse life events had greater shrinkage of grey matter in the PFC, compared to their less-stressed peers. Recent major life events, such as a job loss, make people less emotionally aware while life traumas, such as sexual abuse, seem to go further, in damaging mood centers that regulate pleasure and reward, increasing vulnerability to addiction and decreasing the brain's ability to bounce back.

Then there's menopause.  Had a look at Medscape Today's website.  Estrogen, it seems, protects brain neurons from oxidation, stimulates nerve growth, helps repair damaged neurons, and increases the concentration of vital neurotransmitters such as serotonin, dopamine, and norepinephrine. Postmenopausal women (that would be me) have been shown to exhibit a significant decrease in blood flow, and flow decreases further with time past menopause.  In studies, no significant decrease was attributable to aging alone. (Oh, great, another reason for brain shrinking.) Another study of 63 postmenopausal women before and after starting hormone replacement therapy demonstrated reduced impedance to blood flow in carotid circulation. (that's the artery in your neck that gets gunked up and has to be cleaned out.) Hot flashes, incidentally are related to this function of estrogen.  A hot flash consists of a sudden sensation of heat in the upper body, often followed by perspiration and a chill. Peripheral vasodilation, tachycardia, decreased skin resistance, and sweating have all been documented to occur during a hot flash. Though poorly understood, the episodes certainly originate in the brain.  It now appears that hot flashes are not merely symptoms of low estrogen levels; they may themselves lead to other neurologic problems. (no big revelation to those of us who have had the damn things...) In women without their ovaries, hot flashes have been directly correlated with memory impairment.  In addition, single proton emission computed tomography (SPECT) of healthy menopausal women revealed decreased cerebral blood flow during hot flashes. The greatest change occurred in the hippocampus, a center for memory and cognition. Regional patterns of cerebral blood flow during hot flashes resembled those characteristic of Alzheimer's disease. (Let's not even GO there...) Hormone replacement therapy  resolved the hot flashes and restored normal patterns of cerebral blood flow.  (This is nice, seeing as how after that study a few years back vilifying hormone replacement, no doctors are giving their patients prescriptions for hormone replacement therapy without a threat to their own lives, usually coming from those same patients...OR THEIR HUSBANDS.)

Based on this evidence, reproductive biologists have hypothesized that hot flashes contribute to degenerative or aging changes in the brain. Frequent vasoconstrictive episodes might lead to cerebral ischemia and free radical formation,  damage similar to that seen in the coronary arteries with plaque formation. (Ladies, it's not your high cholesterol or your stress hormones that's going to get you, it's your LACK OF ESTROGEN!) The population of healthy neurons might be reduced, particularly in the hippocampus, leaving the brain with impaired ability to tolerate the neurodegenerative processes of aging and Alzheimer's disease. (Damn, there's that nasty "A" word again...)  Even in healthy older women, brain volume begins to decline as estrogen levels fall preceding menopause. This atrophy occurs particularly in the hippocampus and parietal lobe, areas primarily associated with memory and cognition. A similar loss in brain volume does not begin in men until a decade later (around age 60), most likely because male sex hormone production declines much more gradually with age. In fact, because of aromatization of testosterone to estrogen, men over the age of 60 have approximately three times more circulating estradiol (This is estrogen, folks...) than women of a similar age.  (Is there no end to the unfairness of being a woman on this planet?...in 8 years my husband will have more estrogen than I do.)

In women, these cerebral changes may contribute to the frequent perimenopausal complaints of decreased mental clarity and short-term, verbal memory problems. Many research groups have found   a connection between hormone replacement and cognition, particularly in the area of verbal memory. For example, in one study of 727 postmenopausal women, history of estrogen use was associated with significantly higher scores on verbal memory and abstract reasoning tests.  (Finally, a light in the proverbial  tunnel!! Just imagine how bad my cognitive function would be now if I HADN'T taken those birth control pills all those years...)  

OK, I think I've proved my point.  Hormone replacement is NOT on my allowed medications list.  I have atypical hyperplasia in the breast tissues, which isn't cancer, but the cells aren't normal either.  They are just lurking there, waiting to mutate into something more ominous sounding than "atypical," like "malignant."  Estrogen would encourage them in that direction, so I don't get any.  BIG SIGH.  The depression is less debilitating than it has ever been, due to years of psychotropic drugs and cognitive behavioral therapy, but it has no doubt done some damage.  Stress is a part of life that you cannot avoid; only learn to handle in a more healthy way.  I'm working on that.  The baking powder fiasco aside, I can make it through this.  Crossword puzzles are supposed to help cognitive function.  Yeah, that's the ticket.  If I can find some that don't require an exhaustive knowledge of today's ridiculous pop culture to complete, I've got a solution.....I'll let you know how it works.