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    The Lift of An Alzheimer’s Memory Test

    Eugen G Tarnow  May 2 2016 04:58:45 PM
    The proportion of old people is increasing and with that increase follows an increase in particular types of disease, one of which is Alzheimer’s disease.  If Alzheimer’s disease is not an example of Gompertz’ law (an exponential death rate purely due to age) it might be possible to design drugs that may slow down or even reverse the disease progress.

    In order to put those drugs to clinical trials, symptoms of Alzheimer’s disease have to be easily measurable.  The “gold standard” of Alzheimer’s symptoms, unfortunately, are the results of an autopsy.  Thus “silver” standards have to be used.

    One of the silver standard symptom categories are memory failures.  Alzheimer’s disease attacks the brain and causes damage to the memory.  There is some reason to believe that the damage follows a particular path in the brain and the memory failures would then follow a well-defined path.  It is believed, for example, that the diagnosis of “mild cognitive impairment” represents early Alzheimer’s disease.

    While it is unlikely that damage to long term memory could be reversed by drugs (even if the brain tissue comes back the information is gone), damage to long term memory may be slowed and damage to short term memory may even be reversible.

    But what is short term memory?  Despite what is commonly believed this question is not settled.  Accordingly, there are many Alzheimer’s short term memory tests.

    One of the memory tests most sensitive to Alzheimer’s disease is “free recall” in which a set of words are studied and then repeated.  Unfortunately, words can be “chunked” together, creating larger meaningful units that each are as easily remembered as a single word.  Some of us can chunk words more easily than others so that a word free recall test of ten words can appear to some as just five “chunks”.  Thus test results cannot be compared between individuals and instead would require multiple tests over time to detect individual changes.  

    We at Avalon Analytics wanted to see whether an extremely well defined memory test, we named TUT (Tarnow, 2013), with items that lack meaningful connections would be sensitive to Alzheimer’s disease.  The test items were three double digit integers (the capacity of “working memory” is about 3), the particular numbers selected to make chunking very difficult.  Since the test items were common we thought that they may not be sensitive to education or language.  To lower the statistical noise level the TUT test consisted of three sets of three numbers each.

    We were able to work with the Alzheimer’s Disease Research Center at Icahn School of Medicine at Mount Sinai (ADRC ISMMS).  The 132 participants (Table 1) were part of a clinical study for aging and dementia. Inclusion criteria included 65 years of age or older, primarily English/Chinese/Spanish speaking, visual and auditory acuity adequate for cognitive testing, willingness to participate in all clinical assessment, and having a study partner available as an informant.  Three records indicating dementia due to oncology treatment and vascular dementia were discarded as was a record of a subject who refused to recall more than one number.

    DX
    Frequency
    Percent
    Valid Percent
    Cumulative Percent
    Valid Normal
    83
    62.9
    63.8
    63.8
    MCI
    37
    28.0
    28.5
    92.3
    AD
    10
    7.6
    7.7
    100.0
    Total
    130
    98.5
    100.0
    Missing System
    2
    1.5
    Total
    132
    100.0



    Table 1.  Breakdown of study subjects.

    We found that the participants remembered on average 2.6 items, independent of language (English, Cantonese, Mandarin and Spanish), independent of gender, age and education.

    The participants were diagnosed as normal, Alzheimer’s disease, and two types of MCI (“mild cognitive impairment”).

    The test detected participants with Alzheimer’s disease (remembered an average of 1.9 items versus 2.6 for normal participants) but was insensitive to participants with MCI (remembered an average of 2.5 items).  The standard deviation for both Alzheimer’s disease and normal subjects were 0.6 items.  The probability of a subject in the test population having Alzheimer’s disease as a function of the number of items remembered is displayed in Figure 1.

    The lift is calculated by taking the ratio of the highest target response of 40% from Fig. 1 and the average response (the prevalence of Alzheimer’s disease in the sample) of 7.6%.  This gives a lift of 4 at 20% (the lift below 1 is 0!).

    If we search for a meaning of the result of our very simple memory test it is quite complex.  One of the participants with Alzheimer’s disease had a perfect score on our test.  Thus the loss of working memory capacity for double digits is a common but not necessary condition for Alzheimer’s disease (clinical diagnosis, not autopsy).  Perhaps there are separate working memories for various item categories?  Or is the memory system with the worst symptoms geographically close in the brain to where the working memory for double digits is?  In addition, the participants with the lowest working memory capacity for double digits did not have dementia.  How is it possible to function with such an impaired memory?  Perhaps double digits are just not that important?

    Time will tell.

    Image:The Lift of An Alzheimer’s Memory Test
    Fig. 1. Probability that a subject coming to the clinic will have AD as a function of the TUT 3 item recall.

    Bibliography:

    Tarnow, E. (2013). U.S. Patent Application No. 14/066,195.

    Tarnow, E. (2016). Preliminary Evidence -- Diagnosed Alzheimer's Disease but Not MCI Affects Working Memory Capacity - 0.7 of 2.7 Memory Slots is Lost. arXiv preprint arXiv: 1603.07759.

    Biography:

    Eugen Tarnow is a Director of Data Science at Avalon Analytics (see http://avalonanalytics.com ).  He has a PhD in physics from MIT and have published research in a variety of fields including surveys, marketing, air plane cockpit behavior, and human memory.

    He can be reached at etarnow@avabiz.com
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