all right we'll keep our eye on it dave p tau 217 what are your thoughts

Yeah, so I mean, I think it still is probably the, at least of the sort of biofluid-based biomarkers or certainly blood-based biomarkers, the measure that I think is the most clinically practical that we can get and does, as Chris mentioned earlier, tell us about the likelihood of amyloid in the brain, as well as I think, and there's more and more data supporting the idea, tells us a little bit about the staging.

of the disease as well, or which other biomarkers in concert with it might be particularly helpful.

But one of the other areas that was a major theme of the meeting was this idea that we are heading towards the possibility of drugs that could succeed in preclinical trials of Alzheimer's or trials when people are asymptomatic, two of which we'll read out the next year to two years, and trying to think about how markers that are clinically practical like PTAP 217 might help us in figuring out who patients, who are the prospective people or individuals that would benefit the most from these drugs.

And so there was one very prominent session from a number of groups, including the group at MGH and at Mayo, as well as UCL, University College of London, that presented data demonstrating the predictive value in cognitively unimpaired people for their absolute risk of developing cognitive impairment in the future, which obviously is going to be a really important thing for us to know if we're treating people at a preclinical stage, because you really only want to take a treatment if you're likely to develop symptoms during life.

And I guess what I might say from the sort of take-home from that data is that a measure like PTAU217 does provide a fairly strong amount of risk stratification for the likelihood of developing symptoms at five and 10 years, but are far from deterministic.

did not see any abstracts on memantine.

Yeah.

You know, how does that conclusion of little to no benefit compare with what you're seeing in patients in the discussions you're having about treatment?

I think that's a great question, and I think probably, you know, the really important one which is, you know, how are our patients thinking about these drugs and how do we convey that information to them? I'll, you know, say that when we have these discussions, you know, we're generally basing them on the two approved drugs and their phase three data rather than the conclusions of Cochrane, although it has come up in a couple patients that, um, have heard about these results.

Um, but the real challenge for our field is, uh, I think as Cindy alluded to, is how do we take these, you know, somewhat standardized measures and place this into a context in which a family member and a patient can think about how this may, you know, impact, um, them in the future? And you know, I think what the trials, the two successful trials showed was, you know, about a third, 25% slowing of disease progression, uh, over time.

And I, you know, we try to place that into some sort of timescale.

So you know, over 18 months maybe that's four to six months of, of slowing of the disease relative to where you would've been if you didn't take this drug.

And that often is actually appealing to a lot of patients who are, you know, many, most of the patients we see are in the kind of mild cognitive impairment stage and still by definition functioning fairly well in the, the real world and are, uh, you know, very interested in trying to maintain that level of function for as, as long as possible.

Another thing we, uh, point to is, you know, that trials did try to look at these analyses where they looked at people who progress to a later clinical stage.

And so do you think the balance between risk and benefit was presented in a way that reflects how these conversations between clinicians and patients are actually happening in clinical practice? And I know Cindy and Dave, you both talk to patients about this, and so, you know, how, how do you feel like it was conveyed?