To operate one of London's iconic black cabs, drivers must pass a licensing exam about the city's thousands of streets and the landmarks and businesses associated with them. The grueling test, known as “the Knowledge,” comprises a series of progressively more difficult oral exams in which applicants have to show they've memorized the entirety of London. To prepare, they drive the roads, usually on motorbikes, to learn the shortest, quickest routes and how to get anywhere in the city without the use of maps, either electronic or paper. On average, it takes three to four years to complete the licensing requirement, although some people need even longer.

When drivers do pass, their brains appear to have changed. That's what Eleanor Maguire, PhD, professor of cognitive neuroscience at University College London (UCL), discovered when she scanned the brains of London's black-cab drivers more than 20 years ago. In a study published in the Proceedings of the National Academy of Sciences in 2000, Dr. Maguire and colleagues found that the posterior hippocampus—the seahorse-shaped part of the brain associated with memory and spatial navigation—was larger than normal in the drivers.

A decade later Dr. Maguire reported on another study, which followed drivers for four years as they were going through the black-cab licensing process. She found that among those who passed the rigorous exam, the posterior hippocampus was larger at the end of the four-year period than at the start. By contrast, there was no hippocampal growth in demographically matched subjects who were not cabbies or in the taxi drivers who failed the licensing test. The results suggested that spatial learning and memorization may lead to brain growth, whereas the earlier study's findings could have been skewed if the pool of people who decide to become London cabbies happen to already have large hippocampi. Dr. Maguire's follow-up work provided evidence of neuroplasticity—the capacity of adult brains to grow neural networks in response to learning.

Now another team is repeating the research, with updated tools, to shed light on Alzheimer's disease. “Spatial disorientation appears to be more specific to Alzheimer's disease [than to other forms of dementia],” says Hugo Spiers, PhD, professor of cognitive neuroscience at UCL, who is heading the new Taxi Brains Project. “The hippocampus, which grows in the brains of these cabdrivers, tends to shrink in the early stages of Alzheimer's. Understanding which part of the hippocampus gets bigger when navigating may provide insights into how to develop diagnostic tools for detecting Alzheimer's earlier,” he says. To pinpoint specific areas of the hippocampus that grow with the Knowledge, Spiers' lab is using more sophisticated MRI technology than the original study as well as a game app that tests spatial navigation skills.

Drivers were recruited for the Taxi Brains Project through word of mouth, ads in a taxi drivers' newsletter, and social media, says Stephanie de Silva, a UCL master's student working in Spiers' lab. Tom Hutley, a 30-year-old cabbie who has his own YouTube channel (Tom the Taxi Driver), learned about the study through Twitter. Hutley passed the Knowledge in 2017, after two years and 11 months—and 13 oral exams. In one, he got a route right but forgot the landmarks along the way, and made other mistakes on other routes, too. “They really push you,” Hutley says. On his YouTube channel, he demonstrates a Google Maps challenge: A passenger needs to get across town, and Google Maps specifies a route that would take 39 minutes. Hutley chooses a different route and arrives in 37 minutes—over less distance. Because cabbies charge by distance, Hutley saves his customer “a couple of minutes and a few quid.”

To participate in the study, Hutley completed a questionnaire about his health and lifestyle habits and underwent an MRI. He was then asked to play Sea Hero Quest, an online game developed in 2016 by a company called Glitchers working with Michael Hornberger, a researcher at the University of East Anglia in Norwich, with support from Alzheimer's Research UK and Deutsche Telekom, in which players steer a boat and find sea creatures. The game was designed to predict the ability to get around real places, including London and Paris. While it was available for free through an advertising campaign on YouTube, the game was played by more than 4 million people, creating an international database that allows researchers to investigate how gender, age, location, and socioeconomic status affect navigation performance.

The Spiers lab is measuring how well London taxi drivers play the game compared with the average user, says de Silva. “Future iterations of the Sea Hero Quest app may become a diagnostic tool, identifying people who are at heightened risk for Alzheimer's disease,” she says. Performance on the game may also become an objective way to tell if a particular Alzheimer's drug is working, adds Dr. Spiers.

Dr. Spiers and colleagues are currently analyzing data from the Taxi Brains Project and may publish results later this year. While this study won't be able to identify protective behaviors, that's an important goal for future research. Scientists may learn, for example, that reading maps and memorizing routes, rather than relying on GPS, could reduce the risk of developing Alzheimer's. There's no evidence for it at the moment, says Dr. Spiers, but research groups are looking into it.

Certainly, learning new things is good for the brain. “Staying socially and cognitively active is important in preventing Alzheimer's disease,” says Samantha Allison, PhD, a neuropsychologist in Utah, who has conducted research on spatial navigation and Alzheimer's disease at Washington University in St. Louis. “So are exercise and diet and cardiovascular health, including managing hypertension and sleep apnea.” Navigating streets and cities without relying on GPS might be one way to stay cognitively active, she says.

Hutley would be glad to know his career as a cabdriver is beneficial for his brain, since gene sequencing tests have revealed that he has two copies of the apolipoprotein E4 gene (one from each parent), which increases his risk of developing Alzheimer's disease. Hutley hopes his spatial navigation skill—as well as his hobby of competitive cycling—will help protect him from the condition as he ages. Since passing the Knowledge, Hutley has noticed a difference in how his brain works: “Once I've been to a place and come at it from a different direction, a switch goes off in my brain—the map gets filled in.”