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[00:00:45] Dr. Cecilia Tremblay: Hi, thank you so much for inviting me.
[00:00:47] Dr. Eduardo De Pablo Fernández: So, In the era of wet biomarkers, there is still room and it's still crucial to an accurate clinical examination and I understand that this is what your paper is trying to highlight [00:01:00] here. Your research is, the current analysis is based on the Arizona study Aging and neurodegenerative conditions for those not very familiar with the study.
Can you tell us a bit about the setting the Population and what sort of clinical assessments did they have?
[00:01:19] Dr. Cecilia Tremblay: Yes, of course. We use data from the Arizona study of aging and neurodegenerative disorders in its brain and body donation program, which is a longitudinal clinical pathological study of aging that has been going on for several years at Bannerson Health Research Institute in Sun City, Arizona.
So this is a community based study in which a volunteer elderly participant agrees to longitudinal follow ups with standardized test batteries that includes cognitive movement disorder exams that are performed by subspecialty neurologists. And then volunteers agree to [00:02:00] brain and body and sometimes body donation.
And at the time of that they have a full neuropathological examination. The program focuses on normal aging, so we include cognitively and movement unimpaired individuals, but also focuses on those that have dementia and Parkinsonism. And there's also additional referral from a community neurologist into the program.
[00:02:26] Dr. Eduardo De Pablo Fernández: So it's wide population based cohorts with a mixed of healthy controls and a different neurodegenerative disorders. So in this analysis, you included 652 participants, and the aim of your study was to try to provide a cost effective way to improve the accuracy of Lewy body pathology in clinical practice and clinical research your study focused on two main symptoms, REM sleep behavior disorder and the presence of hyposmia. Can you tell us a bit more about why you focus on [00:03:00] these two symptoms and how were they assessed in your study?
[00:03:04] Dr. Cecilia Tremblay: Yes, of course. We wanted to leverage the large data set that we had. Like collecting data over the years for both REM sleep behavior disorders and olfactory function. REM sleep behavior disorder, which is a parasomnia characterized by dream enactment behavior and loss of REM atonia has been shown to be a really strong predictor of a final clinical pathological diagnosis that involves alpha synuclein pathology.
And while a definite diagnosis requires a video polysomnography which are measures that can be quite expensive and time consuming sometimes clinicians can therefore rely on clinical diagnosis of probable RBD, which has been diagnosed in our program by our neurologist by the history of the participant and we've been also using tools such as the main sleep [00:04:00] questionnaires to help make the diagnosis.
And then also why we selected olfactory dysfunction I've been myself really interested in studying olfactory dysfunction for quite a couple of years now. And I find it really striking how the symptom is quite easy to assess and is really predictive of different neurodegenerative diseases, but especially of synuclein based diagnosis such as Parkinson's disease, dementia with Lewy bodies.
So in our program, we evaluate the olfactory function using the University of Pennsylvania smell identification test, which is a 40 item multiple choice olfactory identification task.
[00:04:45] Dr. Eduardo De Pablo Fernández: So you run this evaluations in a cohort of 652 participants. And can you tell us a bit about the results that you found of the association between these two symptoms and their. pathologies and co pathologies that [00:05:00] you found at the post mortem examination.
[00:05:02] Dr. Cecilia Tremblay: Yes of course. What we did is that we looked at the cases that had probable REM sleep behavior disorders out of the 652 cases, 156 of them had probable RBD. And then we also separated cases that had a lower olfactory function versus a higher olfactory function to see if a lower olfactory function combined with probable RBD would predict a higher percentage of a synuclein pathology at autopsy.
So what we found was that basically when we would combine both markers together if someone had probable REM Sleep Behavioral Disorder and a low upset score, up to 91 percent of them had postmortem synuclein pathology in their brain, which was significantly higher than if we would look at probable REM sleep behavior disorder, which was about [00:06:00] 74 percent of them had synuclein in their brain.
While when we would just look at a low olfactory score, it would be about 70 percent of them that had synuclein pathology. So using both tests what this study told us is that it would significantly increase the specificity. to up to 97 percent when using both symptoms.
[00:06:21] Dr. Eduardo De Pablo Fernández: So, the idea that we get with biomarkers is usually the combination of several of them are more useful in clinical practice than in isolation. One finding that caught my attention is that, as you said, there is a lot of evidence supporting the association between these two symptoms and synucleinopathies.
But one of the results that caught my attention is that Probable REM sleep behavior disorder diagnosed clinically, as you said, and also hyposmia, which we know that it can happen in other neurodegenerative disorders, but particularly the presence of REM sleep behavior disorder was [00:07:00] relatively Frequent in other neurodegenerative disorders, even when you excluded those with Lewy body as a copathology, for example, I think it was about 10 percent of people with Alzheimer's disease without Lewy body as a copathology, and also a smaller percentage about 4 percent of people with PSP.
I don't know if you have any thoughts on that or.
[00:07:22] Dr. Cecilia Tremblay: Yes, we what we found in our population was that probable RBD was a little bit more frequent than what has been already reported by Sleep Study Center. Or study that focus on neurodegenerative diseases, which may suggest that when you consider a broader and less selected population like our population they might have a lower predictive values that is observed for the prediction of synucleinopathy which is increased when you also take into consideration olfactory dysfunction.
Which is, like you said why this is really important to take into consideration more than one symptom, maybe [00:08:00] combined. Like it adds a value to also look at olfactory dysfunction.
[00:08:04] Dr. Eduardo De Pablo Fernández: I think that's a good point that the setting of your studies is more population based and that may explain some of the differences that we can find. With the results that you have, we now know that the combination of reduced smell and probable RBD is highly specific for Lewy body pathology and with a very high negative predictive value.
What is your take home message? What is the utility of this in clinical practice and clinical research?
[00:08:34] Dr. Cecilia Tremblay: I would just say that overall, this work really reinforced the association that, of course it has already been shown, that between RBD and reduced olfactory dysfunction and how it predicts synuclein pathology, but now we do have a validation in a very large autopsy proven series, which is what I think this study really adds to what is already out there in the [00:09:00] literature.
And this really reinforces that reduced olfactory function, even though not specific, may be a useful biomarker when we combine it in a population that may be screened for probable RBD with a simple questionnaire, for instance. And I think this may justify the use of more expensive tests, such as RT-QuIC synuclein assays, or even a sleep study.
In the screening of the general population or for future prodomal studies.
[00:09:30] Dr. Eduardo De Pablo Fernández: That's a very good point here that definitely this can be easily assessed in clinical practice at the bedside and they will be cost effective to be scalable in large populations. Thank you very much Cecilia for your time and your expert discussion about the findings of your study. So I had Cecilia Tremblay discussing her recent paper predicting post mortem alpha synuclein pathology by the combined presence of probable REM sleep behavior disorder and hyposmia, which is [00:10:00] published in Movement Disorders Clinical Practice, and I encourage the listeners to read the full article. Thank you very much, and I hope you found the discussion interesting.
Bye bye for now.
[00:10:11] Dr. Cecilia Tremblay: Yes, of course. Thank you so much.