Current Series: Advances Treatment Alzheimers Disease

Jeffrey L. Cummings, MD, ScD: Ali, I’d like to turn to imaging now, imaging technology. How has imaging technology changed the diagnosis and treatment of Alzheimer disease?

Alireza Atri, MD, PhD: I think imaging and other biomarkers are really exciting. We have fluid biomarkers and imaging that are really allowing us to have a much better accuracy in diagnosing this in life. It used to be that they said, “Well you can’t diagnose it until someone passes away. We have brain tissue.” Now using an algorithmic multi-tiered approach, we can actually see if people have the pathology in their brain. And if it’s in the right clinical setting, it’s more than 99% accurate.

I think about it a different way. If you think about the category of structural imaging, which is something that is almost part of all guidelines, that allows us to both exclude and include the diagnosis. How do we do that? We look at other sources of brain injury, vascular brain injury, and tumors: they happen, but they’re rare. And we caution about that to make sure that you have an understanding that just because the reading comes back on an MRI [magnetic resonance imaging] that says there are age-related changes in the white matter and atrophy, that doesn’t mean that could not have been neurodegeneration and this doesn’t have Alzheimer at the other end of it.

One good scan, MRI, allows us to look at atrophy patterns. In Alzheimer disease oftentimes it could be the medial temporal lobe or hippocampus, or the parietal lobes, can be shrunken early. If that’s there, that’s very suggestive in neurodegeneration. And then in specialized cases, we can look at FDG-PET [fluorodeoxyglucose-positron emission tomography] for metabolism. So again, in Alzheimer disease, there’s a typical temporal and parietal hypometabolism where basically the brain is not revving correctly. And right now we also have amyloid PET scans that can tell us whether there are plaques in the brain, and those are relatively accurate.

The issue with that is that it’s not being reimbursed by insurance very much. Some VAs [Department of Veterans Affairs centers] will actually apparently pay for that. But going down the path, I can tell somebody who really wants a high level of certainty if they have Alzheimer disease, doing this algorithm, that it’s actually due to Alzheimer disease by doing the kinds of profiling, doing the blood work, and doing the MRI. And then I shouldn’t forget the spinal fluid, which is something that isn’t done as much in this country, but really can give us information on whether you actually have the pattern of amyloid and tau in your spinal fluid that’s consistent with Alzheimer disease. That’s a very accurate diagnosis.

Jeffrey L. Cummings, MD, ScD: Anybody else have a different approach to using imaging, or is that pretty much your approach: use MRI first, and work down toward more complicated imaging? Of course, amyloid imaging is very expensive so out of the reach….

Marwan Sabbagh, MD: I’m starting to use the NeuroQuant software or Volumetric software more so than I did in the past, and I find it’s sensitive but not specific. So if you have significant atrophy in the hippocampus, I find that to be informative, but if you don’t, it doesn’t mean there’s a problem. So that’s the thing about it.

Jeffrey L. Cummings, MD, ScD: And of course, atrophy can be a consequence of many different types of neurological disorders.

Marwan Sabbagh, MD: Correct.

Jeffrey L. Cummings, MD, ScD: So it doesn’t establish Alzheimer. But I also agree that it’s very helpful. I find it reassuring if I’ve seen a hippocampal type of memory impairment, and now I’ve got hippocampal atrophy on a quantitative volumetric scan. That’s helpful to me.

Marwan Sabbagh, MD: Right.

Elaine R. Peskind, MD: I take a little bit of a different approach. Certainly, I think every patient getting a first diagnosis needs to have an MRI to, as you say, mostly rule out other causes of cognitive impairment. And if you see some hippocampal atrophy that’s great, but sometimes you don’t. I think for the straightforward typical presentation, you don’t need an amyloid scan. And it’s probably about $7,000.

I think that for atypical presentation, an amyloid scan will be very helpful. FDG-PET is very helpful to make the differentiation between Alzheimer disease, Frontotemporal dementia, and Lewy body dementia, which can all be done with, if you’re lucky, an FDG-PET. And certainly, use amyloid scanning if the patient is able to afford it or if their insurance covers it. But otherwise, for a typical presentation it’s really not necessary.

Alireza Atri, MD, PhD: Interpretation is really important again, because oftentimes if a clinician gets the report back saying “age-related changes,” to then say that it can’t be Alzheimer disease is wrong. So again, the positive predictive value is really high, and to my eye when I look at these scans myself, oftentimes what is read as age appropriate is actually really not. You can actually see clear patterns of atrophy, to my eye, in areas like the parietal lobes or medial temporal lobes that aren’t called.

And FDG-PET I think should be reserved for special cases. But again, I find many, many reads not to be quite accurate. It has to be quite severe for somebody to call that hypometabolism, where to my eye, it’s pretty clear that it’s hypometabolism. So there are caveats with that.

Jeffrey L. Cummings, MD, ScD: I’ve seen the opposite as well where people were diagnosed as having Alzheimer and really the scan was unconvincing and when repeated, was normal.

Marwan Sabbagh, MD: I wanted to add that regarding FDG-PET, there was a paper years ago suggesting that the higher the Mini-Mental State Exam score—meaning the closer to 30—the lower the sensitivity of FDG-PET. And so if you’re in the 25-and-above range, you may have a false negative, when in fact you need to go a little bit lower.