And why you should turn off your GPS

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 like 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 in forming 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 to 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 straight-forward — 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 this paper, 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 US between January 1st 2020 and December 31, 2022 — and all had an occupation listed on their death certificate.

All told, the authors coded 443 occupations and calculated what percent of people in each occupation died from Alzheimer’s disease.

I’ll show you a picture — try to remember it, it’s probably good for your hippocampus.

The graph you see here compares the age at death versus the likelihood of death from Alzheimer’s disease. Right away, you see the correlation — the older you are when you die the more likely you are to die from Alzheimer’s disease. This makes sense — age is the major risk factor for the disease.

Each dot in this graph represents data from one of those 443 occupations. And the line, which I added to their original picture, is the overall average rate of death from Alzheimer’s: 3.88%.

So dots above this line are occupations where people are relatively more likely to die from Alzheimer’s, and dots below are occupations where people are less likely to die from Alzheimer’s.

Taxi drivers appear and ambulance drivers, another group that needs to do a lot of spatial relations work on a day-to-day basis, are here.

The bad news is that the average taxi driver seems to be dying on the young side — a mean age below 70. But even accounting for that, the Alzheimer’s rate is still fairly low. Adjusting for the relationship between age and Alzheimer’s (as well as some other factors like sex, race, and educational attainment) yields this graph — we still see taxi (and ambulance) drivers below the curve.

In fact, those two occupations have the lowest adjusted risk of death from Alzheimer’s disease of any of the 443 studied. Makes me want to start a real hippocampus training program.

But the authors wanted to pressure test these findings a bit. Could this be driven not by the need to form complex spatial maps in your brain, but by the fact that the type of people who do these kind of jobs are, for some reason, protected? It doesn’t seem like it. Other transportation jobs — bus drivers, airline pilots, ship captains, are all sort of middle-of-the-road when it comes to Alzheimer’s risk. It’s worth noting that these jobs, while they require navigating, tend to do that navigation on predefined routes — so perhaps not as much work for the old hippocampus.

Does driving a Taxi prevent all forms of dementia? It doesn’t seem like it. In terms of death from vascular dementia, the second most common form of dementia, taxi and ambulance drivers are actually on the high side. This lends some support to a unique protective effect of hippocampal size on Alzheimer’s mortality specifically.

But we do need to be a bit careful here. This study, as I pointed out at the beginning, included individuals with one thing in common — they had all died. So these findings are restricted to taxi drivers who died compared to other people who died. In other words, if they didn’t die from Alzheimer’s, they had to die from something else to be in this dataset. Which means that the results we see here could actually reflect an increased risk of death from other causes. In the extreme, imagine that Taxi drivers have a 10-fold risk of dying in a car accident. Well, that might mean they are less likely to die from Alzheimer’s — and sure, adjusting for age at death might help a little — but not completely — because it’s possible that the car accident risk holds true across any age.

What I really wanted to see was more than just the two professions — taxi and ambulance drivers — with the lowest risks. I’d like to see the #3 and #4 and so on — let’s see if we can intuit a pattern there that is meaningful — or that reveals some of the inherent biases in this type of analysis.

That said, if we believe the implications of this study, we don’t have to do too much. I mean, yes, we could all quit our jobs and become taxi and ambulance drivers. But if this protection is truly mediated by hippocampal volume — then maybe to prevent Alzheimer’s we simply need to spend more time navigating — less time using GPS — and who knows, maybe get lost every once in a while and try to find our way home.

A version of this commentary first appeared on Medscape.com.