(image of Scrooge McDuck CC by Peter Lee on Flickr)

A newsletter had an article recently about funding for better early diagnostic testing in Alzheimer’s and related dementia (AD).  It’s private funding, with names like Gates, Bezos and Lauder involved.  It’s their money, so why should AlzheimerGadfly be a Scrooge, Bah! Humbug! about it, especially in this glittering holiday season?

From an affected family’s POV, this is the kind of work that we used to scoff at during my short time in a lab: it’s like the drunk looking for his lost keys under the lamppost, at night, because that’s where the light is, missing a bigger picture or better strategy.  I applaud scientific work in general, but money spent there is not spent on therapeutics.

This kind of work avoids the more challenging problems of developing a therapy for current patients here and now, making “prevention” the strategy of patients in the future. Mammography and prostate screening examples of early diagnosis in cancer may not be as effective as one would guess (hence the changing public health guidelines every few years), and in those diseases we have effective therapies to do something about it (or not, maybe, for prostate).

For AD, a consensus “early” clinical stage can be already be defined, called Mild Cognitive Impairment (MCI).  There are no national guidelines for screening, but they’re working on it. Here’s a bit of the National Institute of Aging’s MCI information: 

“Researchers have found that more people with MCI than those without it go on to develop Alzheimer’s. However, not everyone who has MCI develops Alzheimer’s disease. About 8 of every 10 people who fit the definition of amnestic MCI go on to develop Alzheimer’s disease within 7 years. In contrast, 1 to 3 percent of people older than 65 who have normal cognition will develop Alzheimer’s in any one year.”

Mayo Clinic’s information on MCI states that there is no one test for MCI and others say no “disease-modifying” therapeutic approach exists, except the general idea these days is to do exercise (how many steps did you do today?), eat right, challenge your mind, live your best life before you start your inevitable decline, good advice from any grandparent.  But with an early diagnosis, you can have something to think about while you can still think.

What do doctors really do, though?  We were taught that sins of commission might be better than sins of omission, damn the side effects or costs (at least in US medicine, evidently not true in other places). A terrific [IMHO] compact review of therapeutic aspects of AD, by E. Joe and J. Ringman (USC), published just last week in The BMJ, mentions off-label use of meds like donepezil in MCI specifically:

“Timing of initiation of therapy

Although none of the acetylcholinesterase inhibitors is approved for mild cognitive impairment, they are commonly prescribed for this indication in the US. An analysis of 402 participants with mild cognitive impairment in the observational Alzheimer’s Disease Neuroimaging Initiative (ADNI) study showed that 44% were taking acetylcholinesterase inhibitors. This group had a higher rate of decline over two years than patients with mild cognitive impairment who were not taking acetylcholinesterase inhibitors; however, 95% of patients in this subgroup were thought by ADNI investigators to have prodromal AD, compared with more heterogeneous etiologies in the mild cognitive impairment group not taking acetylcholinesterase inhibitors.

The utility of acetylcholinesterase inhibitors in mild cognitive impairment is controversial…..”  The authors go on to describe some clinical trials for MCI, including one with an unexplained increased death rate in the MCI treatment group.  They also review evidence for other AD therapeutics, from medical foods (Vit E is prominent), to exercise, to anti-amyloid monoclonals, etc. Sadly, despite valiant attempts of clinical groups doing the arduous work of mounting trials, nothing has been shown to be disease-modifying (i.e. the way chemo can cure cancer.) Still waiting on Biogen’s attempt to revive aducanumab at the FDA.

When Mr. Gates pledged his $30M last year, I wrote this blog piece: Bill Gates’ $30M for Alz Diagnostics [Jul 2018]: hmmmm…. Probably for nerds only, I mention issues like the chore of test validation (years?), lead-time bias (Will Rogers Phenomenon), and market issues (for a home test, whether it’s good or not, old folks with money will spend, OK Boomer).

Would Scrooge McDuck say “quack quack quack”?  Nah, in this season, he’s no Ebenezer, and Uncle Scrooge loves his nephew ducklings Huey, Dewey and Louie, so he’s gotta say “Happy Holidays Everyone!”