. MRI cortical thickness biomarker predicts AD-like CSF and cognitive decline in normal adults. Neurology. 2012 Jan 10;78(2):84-90. PubMed.

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  1. This paper is very interesting, and another in a series by Brad Dickerson showing that his "cortical signature" set of regions of interest (ROIs) seems to be a pretty good biomarker for AD. I think in the aggregate, the work is impressive—he also had a prior report (Dickerson et al., 2011) that was in Neurology this year showing predictive power of this set of ROIs in two different cohorts—one at Massachusetts General Hospital and the other at Rush. So, in a way, this is the third. I guess this is not so much "novel" as fuel for the already burning fire—supporting the use of a targeted, focused group of brain regions as indicative of AD. I think the main novelty here is the CSF finding showing that not only does this predict decline, but it also seems to be associated with a major Aβ biomarker.

    How will this be used? That is a good question. So far, the main structural biomarkers that seem most widely applied are hippocampal volume and whole brain atrophy rates (i.e., the brain-boundary shift integral [BBSI]—particularly by Nick Fox's group). But I think this is very promising. In fact, we are looking at a similar approach in my lab to see how this does at picking up PIB-positive normals. The ultimate questions are always (1) how dependent are these on the particular cohorts (now that there are quite a few studies with this biomarker, it is beginning to look generalizable, though, of course, the sample of "decliners" is still small); (2) how do the different biomarkers compare (i.e., will this biomarker do better than hippocampal volume, BBSI, FDG-PET, and Aβ measures); and (3) what do markers of neurodegeneration in general tell us that is different from markers of Aβ?

    References:

    . Alzheimer-signature MRI biomarker predicts AD dementia in cognitively normal adults. Neurology. 2011 Apr 19;76(16):1395-402. PubMed.

  2. This is an interesting study that aimed to assess whether a composite measure of cerebral atrophy—called an "AD signature"—was useful in predicting cognitive decline in "cognitively normal" elderly individuals from ADNI. It showed that individuals with lower volumes did indeed have more (subtle) cognitive decline over the following years.

    The "signature" is a composite of nine regions including the medial temporal lobe and a number of other cortical grey matter regions. One point of interest is that even at this early stage of AD (which is likely, but not certain to be the cause of the cognitive decline), the disease either involves diffuse areas of the brain and/or the disease is heterogeneous, with some individuals having a medial temporal lobe-led onset and others a more posterior cortical onset. A second interesting aspect is that this is another study confirming that diffuse volume loss is occurring at a very early prodromal stage (and clearly pre-diagnostic).

    In terms of clinical trials, regardless of whether this particular composite is the one to go for, the study points out the value of multiple regions (or some composite) in tracking early structural change, which is of relevance for the (hopefully soon to come) "prevention trials."

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