Lithium to treat AD?

I was in attendance at the Alzheimer's Association International Conference (AAIC) in Toronto last week, along with about 20,000 other participants. I got to hear the lastest results from the two drugs currently on the market to reduce amyloid: Leqembi (produced by a partnership between Eisai & Biogen), and Kisunla (sold by Eli Lilly). There were some updates to the reported frequencies of side effects, but the general story remains unchanged. Namely, some people develop something called ARIA, which is a pleasant term for a not very pleasant response (brain swelling and/or bleeding). In most cases, ARIA develops with no symptoms (people don't know they have it until one of the check-up MRIs regularly scheduled after starting treatment shows signs of ARIA). When ARIA does develop, it tends to go away by itself when treatment is paused. Lots of people have infusion-related reactions, things like headaches, and shaking / chills. These can be controlled for in future infusions by taking medications to mitigate the infusion-related reactions. Less common infusion-related reactions include nausea, vomitting, fever, and diarrhea.

Alzheimer's Disease is generally characterized as a slow reduction in cognitive decline over time. At AAIC, Eisai presented real-world data on post-FDA approval of Leqembi from diverse US clinical settings. The average patient age was 74, with 51% of the people they studied 75-84 and 4% over 85. They reported that about 84% of the patients on Leqembi either remained stable or clinically improved. It is easy to answer the question about how the group would have declined had they not been on Leqembi. In the Phase 3 trials for Leqembi & Kisunla, about 1/2 the people were taking the active drug and the other half were taking a placebo. In general, those on placebo had declines in cogniton during the trial as they were not taking any active drug for Alzheimer's. The effectiveness of Leqembi & Kisunla in their respective Phase 3 trials was establishing by comparing the cognitive decline of those taking the active drug with those on placebo. The average person receiving Leqembi or Kisunla had slower cognitive decline compared to the average person not taking an active drug.

Eli Lilly presented different data for Kisunla. They calculated something called meaningful within-patient cognitive change. This is their way of estimating the cognitive decline of any one particular individual taking Kisunla, versus if they let nature take its course. They found that over 76 weeks, someone taking Kisunla had a 38% lower risk of meaningful within-patient change over 76 weeks. Another way to state this statistic is that Kisunla reduces your risk of having a reduction in cognition over 76 weeks. Ideally, it would be nice if there was a magical drug that could cure AD. But today, all we have are medications that can reduce your risk of cognitive decline.

I compare the question of starting on Leqembi or Kisunla to gambling at Las Vegas. I am not a gambler myself, but for those who enjoying feeding slot machines, I presume they are hoping they will hit the jackpot and fly home from Vegas with $1M (less a bunch Uncle Sam will collect in taxes). For those of us diagnosed with AD, the question is whether we want to let the disease follow its natural progression, with the cognitive decline we all have seen in our friends & loved ones with late stage Alzheimer's, or try one of the new drugs which have demonstrated in clinical trials that they slow the progression of the disease. For me personally, it was an easy question to answer, I didn't hesitate to start on Leqembi. I was aware of the risks, but I was confident that my Neurologist and the infusion center could handle any situation that might arise. I have been one of the lucky ones, I have had zero reactions to my infusions (I just had my 30th infusion, I started over a year ago). I walk out of the infusion center feeling exactly the same as walking into the infusion center, and go on with my day with normal activities.

Perhaps I should not have posted the article about Lithium Orotate. It never occurred to me that anybody would consider taking such a drug based on a trial with mice. I apologize for my ignorance. I was trying to offer hope for the future, with the possible option of volunteering for a future clinical study with Lithium Orotate for those with a very high risk tolerance and willing to serve as test subjects.

There is an annual paper listing all of the Alzheimer's drugs undergoing clinical trials in the U.S. The 2025 edition listed 138 drugs being assessed in 182 clinical trials. These trials are easily searchable on the clinicaltrials.gov website. Again, I don't understand why anybody would discount these 138 drugs that were approved for a clinical trial by the FDA, and instead take a drug that is in the early research stages and has only been tested with mice.