Four thoughts on how amyloid beta mediates cognitive decline

A new paper addresses the question “how does the presence of amyloid beta (Ab) on neuroimaging correlate with memory deficits?” in a variety of interesting ways. Here are some assorted thoughts:

1) Their strongest direct association (in Tbl 2) is the -0.46 correlation between logical memory scores and Ab positivity on PET imaging in MCI patients. “Positive” status is based on a previously defined threshold basically meaning “lots of Ab.” This is much stronger than the -0.1 correlation between logical memory and Ab positivity on PET imaging in cognitively normal controls. Per their discussion, that Ab correlates well with memory deficits in MCI and not cognitively normal people has been found before, and is rightly part of the justification for why people say that Alzheimers pathology is not normal.

2) This is actually quite nitpicky, since it is not the central point of their article, but to me it’s worth pointing out that the line in their methods, “we examined whether the p value for the association between Ab and cognition changed from significant to nonsignificant when adjusting for GM volume or FDG-PET” is troubling, since differences in significance are not necessarily significant differences. But they address the same question in three ways, and this is just one of them.

3) I like their use of ridge regression in the case of correlated predictors. I became especially interested in how it is a special case of the more general Bayesian ridge regression method, and tried out an example of it, the code for which you can find here, if you’re interested in wasting 1-3 minutes of your life.

4) Stepping back, and although this point has been made before, the general proposition that Ab positivity on PET imaging has a moderate-to-strong correlation with worse memory in MCI populations is a non-trivial finding and is in clear support of the amyloid hypothesis. While it seems that tau correlates more strongly with memory deficits, this is still an important point for those who doubt the AH [1] to keep in mind.

Reference

Mattsson et al, 2015. Brain structure and function as mediators of the effects of amyloid on memory. Pubmed.

Footnotes

[1]: Then again, people may be right to doubt the AH. I’m not trying to use “doubter” in the pejorative sense here. But, I don’t immediately see an easier way to phrase this.

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