I’m returning to the field with my VA house call program. Today was spent in Huntsville, last Thursday in Guntersville, and shortly off to Jasper. If all goes according to plan, I will be adding Childersburg to the list. At that point, if we can get functional teams in Muscle Shoals and Anniston, we’ll be able to offer house calls to every veteran in the Birmingham VA catchment area. If I retire with that having been accomplished, then I’ll think I’ve really managed to do something lasting with my job. Hopefully the stars will align. Who am I kidding? It’s not up to the stars, it’s up to the bean counters in a back office making decisions based on allocated funding and cost benefit analyses. Medicine, like everything else in US society, revolves entirely around money. The first thing I teach medical students when they ask why things are a certain way is for them to figure out who is being paid and how much. That usually answers their question for them.
I don’t have much to report from Covid land. We are over the 600,000 death mark. Only 10,000 more to go to top the Civil War in terms of casualties. We’ll likely hit that by fall as we’re still recording dozens, if not hundreds of daily deaths. The rates around here, which had been falling precipitously through the spring thanks to vaccination, have stalled and are now inching back up due to the number of unvaccinated people in our local communities. While a lot of states are celebrating the 70% level, Alabama remains stalled around 40%. The number of vaccines given the last couple of weeks has been going up, possibly due to the end of school and more free time for people to go get one, but we still need a lot more. We’re now about two weeks out from the long Memorial Day weekend so the hospitalization rate, if its been affected by behavior changes then, should reflect that this next week or so and the death rate will reflect it the first couple of weeks of July.
I’ve run into a number of people recently who have developed Covid these last few weeks despite being fully vaccinated. I’m wondering if that’s the spread of the more contagious and virulent Delta variant. The good news is that studies and anecdotal evidence have shown that if you catch the disease after full vaccination, you may be miserable for a while but you won’t be sick enough to require hospitalization and the chance of death is negligible. The bad news is that as people jettison their masks and learned behaviors for ‘normal’ and more than half remain unvaccinated, your chance of running into the disease remains rather high and, as the Delta variant takes hold and aggressively crowds out other strains, you may get sick this summer. I don’t take foolish chances, but I’m fully cognizant that I am not immune to the vagaries of fate so I’m expecting to feel rotten sometime between now and Labor Day.
The big thing at work, as far as my patients go, has been the approval of aducanamab (trade name Aduhelm), the first new medication for Alzheimer’s disease in decades. There has been some breathless coverage in the lay press aimed at seniors which has got a lot of people worked up about a potential miracle drug for themselves or loved ones. Alzheimer’s disease is one of the scariest diseases out there for most elders. Everyone recognizes it as the disease that destroys the self and, as the self is the most basic concept we have in Western thought, it is absolutely devastating for all involved. I’m rehearsing my gentle speeches for my patients in my head so when they ask, I can let them down gently and explain that the drug is not what they think it is. Most drugs rarely are.
When I entered geriatrics, back in the very early 1990s (30 years ago next month), there were no real medical treatments for Alzheimer’s or other dementias. We tried to control symptoms with various psychoactive drugs, often not very well, but we experimented and learned and stopped doing some of the more destructive things we were doing at the time because we didn’t know any better. Actually, there was one drug on the market for dementia – hydergine. I don’t think they even make it any more as it didn’t work. Everyone knew that the major mechanism in memory involved neurons using acetylcholine as a neurotransmitter and that if you could increase the amount of that chemical in the brain, things should get better. The problem is taking oral acetylcholine is useless – gastric acid breaks it down into acetate and choline which get nowhere near the brain.
People were experimenting with direct injections of acetylcholine into brain ventricles and all sorts of other iffy things without much success until someone hit on the idea of just using the acetylcholine that was already in the brain. Rather than adding more, create a medicine that would prevent it from being broken down in the brain’s constant recycling of materials. Drugs were developed that blocked the enzyme responsible for this breakdown. The first one was tacrine (Cognex) which came out towards the end of my fellowship. It was imperfect. It had to be taken four times a day and it was very toxic to the liver in certain individuals requiring regular blood tests. (Both of these things can be problematic in the demented.) A few years later, better drugs came along with the same mechanism of action donepezil (Aricept), rivastigmine (Exelon) and galantamine (Razadyne). They were not toxic in the same way and could be dosed once or twice a day. None of these drugs is great. They may show down the disease process some for a time, generally not more than a year or two, but they cannot prevent the disease’s slow inexorable march across the brain. But they are something and we use them routinely.
About twenty years ago, one more drug appeared, memantine (Namenda) – it has a very different mechanism of action. It prevents neural cell death by blocking the process of apoptosis – programmed cell destruction. It is only proven to have positive clinical effects in moderate dementia (the point at which someone cannot go into the bathroom in the morning and get ready for the day without help) but again, it’s something. Aducanamab, unlike these other medications, is not an oral drug but rather a monoclonal antibody which enters the brain and prevents amyloid protein (which slimes over and prevents proper function of neurons) from attaching itself and accumulating with time the way it usually does in Alzheimer’s. The clinical trials showed no clinical benefit in terms of improving memory in test subjects, they instead showed a decline in protein accumulation over time. Whether this change manifests itself as any sort of benefit in a living person remains unclear. This is why a lot of experts in the area were against the approval of the drug and a number of people affiliated with the FDA resigned when it was approved as they were so against a drug of such unclear benefit being launched on the world. Monoclonal antibodies must be given as infusions, not as pills. They would be destroyed by the acid environment of the stomach. There are some significant brain bleeding complications in certain individuals requiring routine MRI scans of the brain to detect early problems. Trying to explain infusions and MRIs to the demented can be problematic and the procedures themselves are scary. Then there’s the cost. Biogen has decided $56,000 a year is appropriate. It is unclear which insurances are likely to cover it due to its weak evidence. The FDA has demanded post approval data showing clinical benefit or they will rescind their approval. We don’t know if it will be possible to ascertain this.
Needless to say, it’s not high on my list of things to prescribe to patients. I’ve been laying this all out to patients and families so they have information on which to base choices. We’ll see who opts for the drug and I’ll report back on my clinical experience when I have some.
Life, The Universe, and Everything 