Lithium Could Prevent Alzheimer’s?

Lithium has shown such consistent effects in protecting neurons that several research groups have looked at it for protection against Alzheimer’s disease. Alzheimer’s causes a loss of neurons. Could lithium prevent that? if so, it would be the first medication shown to do so. Given the dramatic rise in Alzheimer’s rates, this is a very important possibility.

The data so far (2014)

First lithium was studied in patients who had already developed Alzheimer’s dementia. It didn’t help. Maybe it’s too late, if the disease has already developed? Maybe lithium could help if it was started earlier?

The earliest signs of Alzheimer’s have been called “Minimal Cognitive Impairment”, or MCI.  People with MCI can tell that their memory is not as good as it used to be, but it’s not seriously impaired.  Okay, right, everyone loses some memory abilities as they age (lemme tell ya’). But MCI is a bit more obvious than that: something’s wrong, but not very wrong. Yes, there is a “spectrum” from normal memory to Alzheimer’s, just like mood is a spectrum from no mood problems to clear-cut mood disorders.

Okay, so the obvious research trial was to take a bunch of people with MCI and divide them into two groups: one gets lithium, one gets a placebo.  Test their memory now, and then test it again in a year. Use a tiny dose of lithium so you’re not taking a big risk (lithium gets trickier to use in older folks). That study was recently done in Brazil. It’s what we’d call a “pilot study”: not as many participants as would be ideal, and not as formal a set of memory tests before and after as would be ideal, but a test of the general idea.

The daily dose was only 300 micrograms. That’s only one-thousandth of the typical lithium pill (300 milligrams).  Yet in a year, it worked to prevent progression toward Alzheimer’s. ^Nunes

If you’re being a good scientist you’d want a second study, by another research group, also seeing the same positive results. But that means waiting another year. Oh wait, there is a second study.^Forlenza  It had a smaller group of subjects, though, and perhaps for that reason, even though the results went in the same direction as the first study, it wasn’t “statistically significant” (meaning, roughly, it could easily have happened by chance).  Interestingly, this second study used a much larger dose, but not “bipolar” doses:

What to do with these two Brazilian studies?  Different doses. Different outcomes. The second is not a replication of the first, and the first one used an unprecedented low dose.Here’s a technical review of all this by the authors of the second study, if you wish. ^Forlenza Note they conclude by asking: “so, are we ready to start using lithium to prevent Alzheimer’s?” and conclude no. Because they are going by scientific and standard medical criteria for judging a therapy. But what if you are facing Alzheimer’s? Might you consider a different standard? One that compares risks, as well as what’s known about effectiveness?

How does lithium protect brain cells?

The short version: it causes an increase in “cell fertilizers” in the brain.  These cause neurons to grow and even reproduce, and works against neuron “atrophy.”

The word “trophic” comes from the Greek root meaning “to feed”. Cell death (atrophy — literally, “not fed”)  because of a lack of such trophic molecules is the working model of how depression changes the brain.  So lithium is promoting cell life in the brain.

More on that in the series of mini-chapters on the Genes, Stress, and the Brain. Start with Chapter 6 to continue the trophic factors story.

Conclusion

For now we can say a couple of things for sure:

1. another replication of these Brazilian studies is desperately needed, because the stakes are very high: are we already in possession of an Alzheimer’s prevention agent?
2. if you take lithium for depression, you may well be getting a brain benefit beyond mood.  You might be getting a brain protection factor. Amazing.

(updated 10/2020)