Alireza Atri, MD, PhDAlireza Atri, MD, PhD
The push in therapeutic development to treat patients at earlier points in the Alzheimer disease and dementia process requires clinicians to better identify patients who are at risk for developing the disease. That of course is easier said than done, as a multitude of factors play a role in how the disease develops and expresses in each individual patient. 

Many argue that monitoring for cognitive health should be no different than monitoring patients for hypertension or heart disease, with consistent screenings used to compare and measure change over time. Establishing this baseline is critically important to our ability to not only help prevent, but to also treat those who experience cognitive decline related to dementia. 

In an interview with NeurologyLive, Alireza Atri, MD, PhD, medical director of the Banner Sun Health Research Institute, spoke about the importance of open-ended cognitive screening, and the value that early detection and intervention can bring to the table. 

NeurologyLive: Are the cognitive screening tests that we use currently sensitive enough, or do they often produce false positives or negatives? 

Alireza Atri, MD, PhD: I think the most important aspect of that is there's no one size fits all. And taking the concerns of individuals-- if they notice changes or symptoms in themselves, that's really, really important. It's also important to not take as gospel one cut off for any particular test. For example, in neuropsychological testing, you can have individuals who are very bright, very accomplished, very educated, and they would have to fall a lot and have a lot of damage accrue before that may be reflected even in in an instrument that's used very commonly like the MoCA. They could actually be at a level where they're not functioning like they did, and they need support and even be at the dementia level with their behavior or judgments and yet score well on a what we call brief, standardized kinds of test. So, it's not that we don't have instruments--I think you have to start somewhere, but not take the test results as gospel if you think that people are still scoring kind of normally, or be a bit more in tune to if they're missing points, where it is and what the pattern of that is. In primary care, it really depends on the proficiency of the clinician. What instruments they like to use, knowing the limitations of those instruments, and for people who are those extremes of age, education, language, or maybe they're behavioral syndrome isn't as well captured in some of those instruments, to know who to refer to and how, and I think neuropsychological testing with somebody who knows how to do this well and interpret it well is really important.

As a neurologist and sub-specialist neurologist like myself, we have other things in our toolkit--it's not just the MoCA. We have other tests that we can even give at the bedside, including tests of memory, cognition, executive function, etc. At that point if I'm still concerned because the pattern of maybe a point here or a point there is a little bit off, the gold standard really is a really good neuropsychological evaluation. It's not just testing, it's a whole evaluation.

Recently, the American Academy of Neurology issued a new quality measurement for annual cognitive assessments for people age 65 and older regardless of whether they are showing signs of impairment or not. How do you feel about that?

It's long overdue. The US Preventative Services Task Force for years has said well, there's no level 1 data to advocate or not advocate for this. Well, the fact is that there's no level 1, randomized, double-blind, placebo-controlled trial data that says that you shouldn't smoke or that you should use a parachute if you're going to jump out of a plane. I mean, it goes against so much clinical sense and common sense--just because those studies haven't been funded doesn't mean that there's no value in doing it. And that goes for screening in the general public. If you have patients who are coming to a neurologist for a problem related to the brain, the AAN is recognizing that that in itself is a risk factor for cognitive impairment and dementia. So there's the the element of screening, which is doing it in people without risk or you can have detection or stratified screening, or you can go about it based upon concerns. The Alzheimer's Association clinical practice guidelines really defines the screening pathway as starting with a concern for a change about anything from anybody--patient, informant, or clinician, that's a good place to start.

It's very different when you're sitting there as an epidemiologist as opposed to people like me who take care of patients and families. I understand data. I have a PhD in bio math. I've done 3 postdocs, and I do quantitative work, but I also understand evidence. They say, you know, there's no evidence here and there's gaps in the evidence, but you can't ignore the wealth of data and knowledge that the practitioners have. They also say that what there's no evidence that detecting it helps you with anything; that's just so wrong. There's no face validity to that to say, gosh, you can detect an impairment in cognition or behavior, but that's not a value. What does that even mean? You're telling people to take medicines and manage their own conditions and that is why they end up at hospitals and emergency departments.

We're increasingly focused on targeting therapies earlier and earlier. How does the frequency of those cognitive assessments fit in to that therapeutic model? 

People should have baselines. You should know where you're coming from so you can detect change. That's the part that's important. Why do we take someone's blood pressure? Because we can then detect if there's a change. So it's in the same vein; it's really important to establish baselines to begin with. Then when there are issues that are really subtle and early, people can have an opportunity to have maybe a more detailed baseline, a more accurate baseline, and then have the opportunity to go into clinical trials like for BAN2401 or prevention trials like A3 and A45 depending on if they have amyloid in there brain, or maybe they want to go into a multimodal exercise program, a mindfulness program, or a nutrition program, but at least it allows people to have the autonomy to be the masters and mistresses of their own fate early on where they can make decisions as opposed to when it's really late and they can't participate as well in their care.

What are your thoughts on sub-threshold amyloid in light of trying to identify patients early in the disease process for intervention? 

So the word sub-threshold is interesting, right? Very few things in life are binary: death, pregnancy--even those things we get wrong. So really, everything's on a continuum, yet we've decided to draw a line somewhere. We're drawing a line on something that we don't understand its full implications in the brain, because amyloid is only one component. So for any person with a given amyloid level, which could be lower, they may have more inflammation in their brain, they may have vascular changes, and those things all together additively and synergistically can impact synaptic dysfunction and neurodegeneration. It's always a balance between our own resilience factors and vulnerabilities and the other conditions and pathologies we have. So if we leave it until late in the disease process, and only say we're going to treat people with the highest levels of amyloid, we're ignoring the effects on neurogeneration and synaptic and network dysfunction.

Transcript edited for clarity