December 9, 2005

  • One of the advantages of having your work as your hobby is that you get
    to do it all the time.  Of course, the disadvantage is that you
    have to do it all the time.

    One of the enjoyable sides of statistics this fall has been shifting
    over from Splus to R.  R is open source (read "FREE"), but
    maintained by some very smart people (who provide a lot of code for
    Splus as well).  I can do nearly everything I want in R and I
    don't have to fight with the Splus license manager to be able to do
    it.  There are a few occasional perks of Splus that I miss - but
    since they've decided in the last couple of years to focus on the
    people with the big bucks (financial institutions, drug companies), I
    don't really miss much.

    Today I've been working on a project that involves looking at two
    cognitive tests that were done in several hundred women who were at
    different stages of the menopausal transition.  The tests work
    like this.  An interviewer reads a brief story and then asks the
    interviewee to name as many story elements as they can.  There are
    12 elements that are scored, so everyone gets a score from 0 to
    12.  This is called immediate recall.  The interview goes on
    to other items and then, a few minutes later, the interviewer repeats
    the question (this is called delayed recall - sneaky, isn't it?) and
    notes how many elements the interviewee can remember.  Got
    it?  On average the women in our study could name about 10 of the
    12 elements.  Pretty good!

    The part of the brain that is working when we do immediate and short
    term memory tasks like this involves the prefrontal cortex (which is in
    the front of our brains).  This part of our brain happens to have
    more estrogen receptors (ie things that make cells sensitive to the
    presence or absence of estrogen), so it is reasonable to think that
    this type of memory might reasonably be enhanced (or not) as a woman's
    estrogen balance changes during the menopausal transition.

    Everyone wants to know if there are differences in the level of
    functioning and, if so, what those are.  Some colleagues out in CA
    had been working with this data and had not found any significant
    differences.  I recently started working with the same measures
    (immediate and delayed recall), looking at the relationship between
    various genotypes found in blood samples and scores on our memory
    tests, and realized that there was a better way to approach the
    analysis of these measures of immediate and delayed recall.  My
    colleagues were thinking of them as a continuous score on a scale of 0
    to 12 and examining means and standard deviations as if they were
    normally distributed (as in "bell-shaped curve").  The problem
    with that approach is that there is a clear "ceiling effect" - that is,
    you can't get more than 12.  So, you could have a standard
    deviation of 2 and a mean of 10, but you would never be able to get 2
    standard deviations above the mean (10+2*2=14), because the maximum
    score is 12.  That's bad, because in a normal distribution you
    would expect to see about 15% of your people have scores above 12.

    Another way of thinking about it is like 12 flips of a coin.  How
    is that?  Well, there are 12 elements and the interviewee either
    succeeds (heads) or fails (tails) to name each one.  Statisticians
    call this kind of collection of successes and failures a binomial
    random variable.  There is the tacit assumption that the
    probability of successfully naming each element is the same, which is
    not strictly true.  (Some are probably easier to remember.) 
    But as a famous statistician (I think it was Dr. George Box) once
    pointed out:  "All statistical models are wrong!  But some of
    them are useful."  In this case thinking of the test results as a
    binomial random variable is more useful than thinking about it as
    having a normal distribution with a mean and standard deviation.

    Cut to the chase.  When you treat the results using means and
    standard deviations, there are no significant differences. 
    However, when you treat it as flips of a coin, there are significant
    differences, even after you adjust for a whole bunch of other things
    that are also related to cognitive functioning (age, education,
    ethnicity, BMI, poor health, vasomotor symptoms, poor sleep, somatic
    symptoms, mood symptoms, estrogen levels and FSH levels).  The
    primary finding will be that there is a small but significant decrease
    in the number of elements named by women who are post-menopausal
    compared to those who are late peri-menopausal.  And the effect is
    significant at the 0.001 even after adjusting for multiple comparisons,
    which is statistician-speak for "WOW!".

Comments (4)

  • Wow Mr. Meyer, you made that very accesable for the non-statistician. I can now give statistical affirmation to my mother's forgetfulness :) (I see where Joel gets his brains)

  • Wow, that's really cool. What provided the insight that thinking of it as a binomial random variable would be better? I'm with Jeff - that was very accessible to a statistically-impaired person like myself

  • I personally enjoyed Dr. George Box's quote--it makes me feel better about myself and my statistical ineptitude. By the way, I'm just curious, but do you know of any research detailing the cellular/molecular mechanisms of estrogen activity in the prefrontal cortex (and possibly hippocampal formation)? Memory is always interesting and the deeper you go, the more interesting it can get...besides, those of us who aren't quite as intelligent can deal with that better than statistics.

  • My favorite article (out of a very limited reference list) is: Shaywitz, S. E., B. A. Shaywitz, et al. (1999). "Effect of Estrogen on Brain Activation Patterns in Postmenopausal Women During Working Memory Tasks." JAMA 281(13): 1197-1202. It's a fascinating article using functional MRI to detect areas of the brain that are activated during various cognitive tasks. The following article sheds some light on the sex/developmental aspects: Gorski, R. A. (1999). "Development of the Cerebral Cortex: XV. Sexual differentiation of the central nervous system." Journal of the American Academy of Child and Adolescent Psychiatry 38(3): 344-346. I found one other article in my reference manager, but I don't remember if it was helpful or not: Zola-Morgan, S. and L. R. Squire (1993). "Neuroanatomy of memory." Annu Rev Neurosci 16: 547-63.

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