What Lies Ahead for Dementia Therapy

Andrew N. Wilner, MD


June 10, 2019

While attending this year's annual meeting of the American Academy of Neurology (AAN), Medscape contributor Andrew Wilner, MD, interviewed Bradley F. Boeve, MD, professor of neurology at the Mayo Clinic in Rochester, Minnesota. Boeve noted that although this year's meeting failed to produce any relevant advances in dementia therapy, there is still much to look forward to in the years ahead.

A Transitional Meeting

I think we're all somewhat frustrated in the clinic with what we have to offer our patients with Alzheimer disease and other dementias. Did you see anything here at the AAN meeting that was encouraging?

It seems like it's a transitional phase right now, given the disappointing recent results from the antiamyloid therapies, mainly the amyloid immunotherapies such as aducanumab.

One question this raises is, are these therapies doomed to fail no matter where they're given in the course of Alzheimer disease pathogenesis, or are we giving them too late? There's still enthusiasm that earlier in the course of disease, in the presymptomatic phase, they may be effective. There are trials pursuing that, although that's a pretty controversial subject.

Is it correct that we now believe that someone clinically diagnosed as having Alzheimer's probably has had that disorder for at least 10 or 20 years?

Yes. A big question in the field is still how amyloid induces or is in any way related to the tau. There must be a relationship, but that tangled pathogenesis is still being sorted out.

But the pendulum does seem to be swinging. There wasn't a whole lot presented at this meeting, but there were a lot of discussions about movement in the symptomatic phase for primary tau-based therapies. Progressive supranuclear palsy (PSP) is a good prototype for the primary tauopathies. Because PSP is relatively easy to diagnose by a neurologist and also has a frustratingly rapid rate of progression, a signal should be apparent over a relatively short period of time.

There are programs being developed for the use of tau as a target in Alzheimer disease. It's still in the fairly early stages, so there weren't many results presented at this meeting. However, future Academy meetings will surely have them.

Do you think there's anything in the pipeline that we're going to see next year for our patients with Alzheimer disease?

There may be some updated results soon on the Eisai compound, BAN2401. I don't know if they'll have the results ready for presentation a year from now, but that one still seems to be going. That's probably the primary amyloid agent still in progress in symptomatic Alzheimer disease.

Enabling Earlier Diagnosis

Even if we could find a treatment that was effective early, do we have a way to diagnose patients early?

It looks like the biomarkers are quite compelling. It is hard to do it in the clinic yet, because a lot of these things aren't reimbursed—at least tau and amyloid PET imaging isn't. It is available, though it's rather expensive. Cerebrospinal fluid (CSF) biomarkers look relatively inexpensive compared with PET imaging, and quite solid, with the low amyloid/high phospho-tau being solid biomarkers for Alzheimer disease. In the mild cognitive impairment phase, those look quite good.

In the presymptomatic phase, this assessment is not done routinely in the clinic. We should be doing CSF or PET imaging in the presymptomatic phase, and that movement very likely will happen if it's shown that any of these therapies are efficacious and safe in the symptomatic phase.

I think as soon as we have an effective treatment, our efforts will be directed to early diagnosis; that'll be a priority.

Exactly. Then when it comes to other therapies, such as gene therapies and antisense oligonucleotides therapies, and more novel therapeutics that affect synaptic functioning (synaptogenesis), those are still in the early stage. But it seems like there's more and more interest among smaller companies to go in that direction. So we'll have to wait and see.

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