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Do the mild memory problems (senior moments) of older people signify greater risk of Alzheimer’s?
(January 2007)

The answer to that question is potentially yes according to an article in the journal Neurology in June 2006.  This is a very thorough and sophisticated study of more than 2,000 older people who agreed to donate their brains for study after death.  They were examined annually with a huge battery of tests to measure thinking capacities and memory (cognition) using 18 individual tests.  They were also examined for dementia and cognition problems annually by nurses, physicians, and neuropsychologists.  During the followup period, 134 persons died who did not have clinical or testing evidence of dementia or cognitive impairment - that is, they seemed mentally normal.  When the brains of these 134 men and women, average age at death about 83 years, were examined, about 37 to 45 percent (depending on the criteria used) met the pathologic definition for probable or definite Alzheimer’s Disease, even though none had manifested any obvious dementia during life.

Those with a high likelihood of or probable Alzheimer’s on brain examination were compared with those whose brain showed no such abnormality in regard to the 18 specific cognition tests done repeatedly during their lives.  Those with pathologic evidence of Alzheimer’s generally had somewhat lower scores, but not by much, and the authors make nothing of these small differences.  Then they did a sophisticated statistical test called linear regression on the cognitive test results, combining the tests into five categories.  One of the five categories called episodic memory was significantly reduced in those with probable or definite Alzheimer’s..  That category consisted of seven individual tests, including the ability to recall a story and word list memory and recall.

The authors were impressed by the linear regression findings in people who, at death, had brains showing probable or very likely Alzheimer’s despite no evidence of the disease during their lives.  They noted “these data suggest that even slight impairment of episodic memory in older persons may signify the presence of pathology (Alzheimer’s) rather than representing a normal consequence of aging”.

Commentary: This is a very interesting and well-conducted study.  The media have jumped on the results to proclaim that inability to remember a name or a particular word (“senior moments”) should raise a concern about developing Alzheimer’s.  That is over-reaching for the following reasons:

-           The individual cognitive test differences between those with pathological evidence of Alzheimer’s and those with normal brains were quite small and unimpressive.  So, it is a question of whether to focus on lack of major differences in individual tests or on the significant differences in the linear regression test combining multiple specific testss; the authors chose the latter.

To get values for average scores for the group for each cognitive test, the individual scores for each individual on the multiple annual evaluations were averaged, and then all these individual averages were averaged to get a group score and then in the multiple regression analysis for “episodic” memory, the seven individual tests were lumped together.  That leaves a lot of room for drawing a wrong conclusion.  It also takes small differences in individual tests, adds them all up, and achieves statistical significance - but, there are still only small differences in individual tests.
-           The regression analysis adjusts for differences in age, gender, and education, but not for nutrition status.  It is possible that these very old individuals could differ in regard to folic acid, B12, and B1 (thiamine) status and those differences, not early Alzheimer’s, could account for some of the small differences on the cognitive tests relating to “episodic” memory.

-           We really need to know the pattern of individual responses over time in those with apparent Alzheimer’s Disease at autopsy.  Since, in life, they had no behavioral evidence of Alzheimer’s, but did appear to show (on linear regression) defects in cognitive function (in episodic memory), the question is did their scores on the seven individual tests deteriorate from year to year.  That would give us a lot more information than that provided by the linear regression lumping all the individuals, all the individual test scores, and the seven separate tests.

This is very interesting and potentially important, but it is just the beginning.  We need a lot more information before drawing any conclusions.

Bennett, D.A., et al.  Neuropathology of older persons without cognitive impairment from two community-based studies.  Neurology.  Vol 66 (June) Pgs 1837-1844.  2006.

Now the critical issue for the public.  Should we worry (or assume) that our “senior moments”, for example, not coming up with a name or a word, are not benign and signify increased risk for or the presence of very early Alzheimer’s?  The answer is a firm no.

There are two points to make.

First, of course, most of those who develop Alzheimer’s will have a period of months, or more likely years, of subtle then greater decline in thinking and memory.  They would be expected to show lower scores in cognitive tests.  However, since these people whose brains showed Alzheimer’s had no evidence of mental troubles into their 80s, this study would actually suggest that, for many, Alzheimer’s can be a mild disease that will not trouble them even if they live to an old age.  If that is true, it is fascinating and changes our picture of Alzheimer’s as always an inexorable, terrible disease (which it often is).

Second, there is no documented linkage between results on these cognitive tests and “senior moments” which affect a large proportion of the population starting at age 50 or 70.  “Senior moments” are not the same as big decrements on cognitive tests and do not have the same significance as, for example, not remembering where you live or where your supermarket is.  “Senior moments” do not presage Alzheimer’s.  They are still part of the normal aging process, to be regarded as trivial annoyances and to be treated with a bit of self-conscious humor.  If they progress to, for example, not remembering where you live or the names of your children, or to overall obvious thinking problems, that is the time to worry.