The future of Alzheimer’s disease: blood biomarkers, brain imaging, and screening the cognitively unimpaired

Thank you very much, everybody, for introducing yourselves.

It's very useful to have some background context.

Cliff, this series takes what you call a futuristic look at practice five to 10 years from now.

Forecasting in this field has been humbling.

Anti-amyloid trials failed for years before the recent approvals.

So what gives you confidence in these projections and what would prompt you to revise them?

So what would prompt me to revise them may seem like a strange response, but

nothing.

So I think that what has been written in these three future-looking papers are very accurate, and I don't think any revisions would need to be made at the present time.

What gives me confidence that now, having said that, there's a difference between future planning and actual operationalization.

Operationalization of biomarker screening in asymptomatic people, imaging in asymptomatic people, the kind of triaging that Jonathan's going to discuss in detail.

That operationalization may have to be moved further into the future than 5 to 10 years if the current group of trials do indeed fail to demonstrate clear-cut clinical benefit.

But I think most people on the field believe that treatments for asymptomatic people with the disease are inevitable.

And why is that? And that's because the logic underlying such an approach is so compelling.

The logic underlying prevention of irreversible neurodegeneration prior to the onset of symptoms is undeniable.

And it's not going away.

So one of the striking things about the series is that your writing groups were open about not reaching consensus on whether a cognitively unimpaired person with amyloid and tau pathology has a disease or a risk factor, So how did you go about building a clinical pathway and screening workflow while that question is still genuinely open?

Yeah, I think it's important not to overstate the disagreement.

There was actually far more agreement than disagreement amongst the writing members.

For example, we all agreed that biomarkers are becoming increasingly important and that individuals at risk of cognitive impairment can be identified earlier than before.

And that if these prevention trials that Cliff alluded to demonstrate meaningful clinical benefits, that health care systems really need a plan for how to identify and potentially treat these individuals.

So rather than wait for every terminology debate to be settled, we really focused on a practical question.

If these trials are successful, what should these clinical pathways look like? And our goal was to be transparent about where the disagreement exists while also preparing for a future that might arrive sooner than many people in the field expect.

Thank you for clarifying.

So another concern raised about biomarker first frameworks is that they risk medicalizing aging itself, creating a large population of patients in waiting who may never become symptomatic.