. Ten-year change in plasma amyloid beta levels and late-life cognitive decline. Arch Neurol. 2009 Oct;66(10):1247-53. PubMed.


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  1. This study is clearly of interest, supporting the idea that a lower plasma Aβ42 to Aβ40 ratio (i.e., a higher Aβ40 to Aβ42 ratio in this study) may be associated not only with an increase in risk of developing dementia, as previously described by us and others, but also with a faster cognitive decline in global cognition in the elderly. This faster decline was detectable even at a very early stage in “midlife” (63.6 +/- 2.4 years), 10 years before the first cognitive assessments.

    This paper provides further evidence that something is happening with Aβ peptides in plasma, even if we still do not know from where these Aβ peptides are coming.
    Particularly, if these plasma peptides are not representative of the brain production as previously suggested, this raises the question of why and how the Aβ peptides produced in other organs may be indicators of cognition functions and risk of dementia.
    Furthermore, if the Aβ42/Aβ40 ratio is more than a marker, what are the physiological and perhaps pathophysiological roles of these peptides in plasma?

    However, it is also clear that the associations observed in this paper are weak. The study design suggests an oversampling of participants (only women) from the top and bottom 20 percent of the distributions of cognitive decline. It will be necessary to replicate these results in other large prospective population-based studies; we are currently performing such analyses in the 3C Study.

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