MRI assay for early signs of Alzheimer’s

Yesterday we considered a paper that potentially lays the foundation for a microarray-based blood test for Alzheimer’s disease (AD). With that in mind, I couldn’t help but notice a recent announcement of another promising technology for early AD detection, this time from the field of medical radiology. (I knew I was reading a medical journal because the authors actually include their MDs alongside their names, a cultural quirk that we PhD’s don’t share in “our” journals, and which we find the slightest bit touchingly amusing).

Ray (MD) et al. report that a parameter called the apparent diffusion coefficient (ADC) — a measure of how rapidly small molecules diffuse through a medium — differs significantly between patients with mild cognitive impairment (MCI, often a precursor diagnosis to AD) and those with normal/healthy brains.

Materials and Methods: Magnetic resonance (MR) imaging was performed in 13 patients with MCI (nine men, four women; mean age, 74 years ± 6 [standard deviation]) and 13 healthy elderly control subjects (seven men, six women; mean age, 75 years ± 4). … ADC was measured from manually drawn regions of interest (ROIs) of the hippocampus, parahippocampal gyrus, amygdala, corpus callosum, and anterior and posterior cingulate gyrus and from automatically defined frontal, parietal, occipital, and temporal lobes by using template masking. …
Results: Higher ADCs were found in hippocampus, temporal lobe gray matter, and corpus callosum of patients with MCI compared with that of control subjects … By pooling all subjects together, an elevated hippocampal ADC was significantly correlated with worse memory performance scores in 5-minute and 30-minute delayed word-list recall tasks …

So MCI correlates with higher ADC. Translating from alphabet soup: cognitively impaired brains allow a freer flow of small molecules through the tissue, as though the cells were less tightly packed together; this is what one would expect if the brain had suffered significant cell death.

Such an assay (especially if deployed alongside the microarray-based diagnostic we discussed yesterday) could conceivably be used to detect the earliest stages of AD, allowing earlier treatment and better patient care.

Both techniques have a good deal of scatter, and that the significance of the findings emerge when comparing one clinically well-defined population against another. The uncertainty inherent in statistical endpoints of this kind limits the usefulness of a tool for the diagnosis of a specific patient at a specific time, and in some ways takes us back to where we started: “on the basis of this test, you are 80% likely to be in the earliest stages of the disease.”

I therefore speculate that technologies of this sort will have greater diagnostic value if measurements could be prepared against a patient-specific baseline, taken years earlier. The physician would then be looking at the change in a parameter over time in the same individual, rather than trying to glean information from a single snapshot of that individual and its relationship to the distribution in well-defined populations.

Thinking more broadly: Almost any measurement of tissue function as it relates to age would be more powerful if the individual baseline had been regularly assayed over the years (decades?) previously, a point to keep in mind as we sketch out the plans for medical lifespan extension.