We still don’t know exactly what causes Alzheimer’s disease. We know there are certain genetic and environmental risk factors, and of course, we know what the brain pathology looks like, with the characteristic amyloid plaques and neurofibrillary tangles. We know that it is progressive and, barring death from another cause, fatal. Some medications have been developed, though the track record for success is pretty poor. It seems that perhaps the best way to treat Alzheimer’s disease is to never develop it in the first place. But do we even know how to prevent it?

A new clue to that particular puzzle comes this week from a most unlikely source: taxi drivers. But I can’t explain why taxi drivers seem to be protected from Alzheimer’s disease without first talking about the hippocampus.

Deep in the brain, on the floor of the lateral ventricles and abutting the medial temporal lobe, you’ll find these structures which 16th century anatomists thought looked something like a seahorse — hence, hippocampus, from the Latin.

This part of the brain is critical for converting short-term memories into long-term ones. If you’ve seen the Christopher Nolan film noir Memento, you have an idea of what a problem with the hippocampus can look like. For a real-life example, we need look no further than to Henry Molaison, a Connecticut native with severe epilepsy who had both hippocampi removed surgically and subsequently lost the ability to form new memories. It’s a fascinating story and one that gave real insight into a complex bit of brain functioning.

The other main function of the hippocampus is to form spatial memories, our ability to navigate in a complex way.

And the hippocampus is inextricably linked to Alzheimer's disease. It is the first brain structure that starts to deteriorate in the disease, leading to the characteristic early symptoms: poor memory and spatial disorientation.

With that introduction to the seahorse living in your brain, we turn to the real subject of this discussion, taxi drivers. Taxi drivers are special people when it comes to the hippocampus. A seminal study in the year 2000 used MRI to scan the brains of 16 healthy, male, right-handed taxi drivers from London — a notoriously complex city to navigate — and compared them with 50 healthy, male right-handed regular people.

The taxi drivers had significantly larger hippocampi, and the longer they had been driving the taxi, the larger the hippocampi were. The conclusion was straightforward: These guys’ hippocampi were working overtime to keep track of where they were in the sprawling city, and, like any muscle used frequently, were getting bigger as a result. (As an aside, these results could also mean that people with naturally larger hippocampi are more likely to end up as taxi drivers — but we’ll drop that thread for now.)

So, if Alzheimer’s disease starts in the hippocampus, would people with really strong hippocampi be protected from Alzheimer’s disease? That’s the subject of a paper, “Alzheimer’s Disease Mortality Among Taxi and Ambulance Drivers: Population Based Cross Sectional Study,” appearing in The BMJ.

In contrast to the very small MRI study, this paper is huge, encompassing 8,972,221 individuals with one thing in common: All of them died in the United States between January 1, 2020, and December 31, 2022 — and all had an occupation listed on their death certificate.