Bottom line:  the optimistic view is that there may be hope in a sub-population of a small human study looking at inhaled insulin, but if one looks at the official Press Releases and Awards, news of substantial or imminent clinical help for patients with Alzheimer’s or dementia is notable in its absence.

I did not attend the AAIC19 meeting in LA that just finished, although I felt justified in commenting on this blog about the lifestyle and prevention papers that were presented there, because those actual peer-reviewed articles were made available online. Big meetings in medical science are important, and I used to go, as a member, to ASH, ASCO, Children’s Oncology Group and ASPHO meetings whenever I could.

I like looking at the Awards, because the recipients have spent their whole careers trying to deal with this frustrating arena, and should be acknowledged and lionized.  The Award category also lists young investigators and their work, which is also encouraging.  But out of the eight awards for student and post-doc posters, only two were for therapeutics, and only in rodent models.

Of course, given the duration and elaborate complexity of human clinical trials, it would be surprising for a student or post-doc to have results to share or present at a big meeting.

The headliner in their Clinical Trials press release was an inhaled insulin study with a curious report of several stages.  The first stage used Device 1, comparing regular insulin with placebo, had 49 subjects, and seemed to have positive impact on measures of cognition, abilities (ADL) and even in CSF biomarkers, but the overall P-value was a non-statistically significant p=0.091 [Did you see that NEJM is trying to drop P-values in their research articles?]

The press release writes that Device 1 “had inconsistent reliability”, so the study went forward with another 240 subjects with different Device 2.  Unfortunately, there was “no benefit” detected for the larger Device 2 group, even with another 6 month stage of an open label extension.

So the study, to me, has a puzzling ad hoc “design,”  and the press release of course is not subject to peer-review or much scrutiny.  On the other hand, a few subjects really seemed to get better (including biomarkers)!  Was that some kind of statistical fluke, or selection bias, or unknown factor, some luck or magic provided by the unreliable Device 1?  A wag might say that it was just the therapeutic magic of sneezing, or that we need to include nasal mucous as an amyloid disposal route, or that the olafactory bulbs must have special cognitive neurotransmitters!  A desperate empiricist doesn’t care. Treat now for effect, figure it out later.

The fact that anyone seemed to improve seems worthy of a deeper dive.  I would guess that the investigators will more fully characterize the responders (the way some cancer treatment trials are analyzed).   Yes, there have been some “responders,” (at least as I interpret the papers) on some testing and serial PET imaging in anti-amyloid immunotherapy and BACE agents trials that were ultimately considered clinical failures.  This is the study Alz Assn PR people chose to highlight, so let’s hope the investigators can tighten things up and deliver!