KRISTINE YAFFE

By Hannah Ongley

Kristine Yaffe is a pioneer in the field of geriatric psychiatry, melding the discipline with neurology and epidemiology to better understand brain aging and dementia. Fascinated early on with the relationship between brain function and behavior, Kristine trained in neurology before pursuing a second residency in psychiatry. This path might seem straightforward today, but it was unconventional at the time, met with resistance from some of her colleagues. “Medicine in a lot of the world can be very paternalistic, hierarchical, infantilizing,” she recalls. “People would say, When will you be done with this foolishness? And I’d say, Foolishness?”

Kristine’s research challenges the status quo in terms of how medicine is performed in the US. Today, she is the foremost leader in identifying modifiable risk factors for dementia, heading the Center for Population Brain Health at the University of California, San Francisco. She recently led the ambitious Systematic Multi-Domain Alzheimer’s Risk Reduction Trial (SMARRT), which examined how personalized behavioral interventions might help individuals reduce their dementia risk and slow cognitive decline. Kristine highlights the need for a more integrated approach to brain health—one that combines medicine with lifestyle interventions. “Part of the challenge is that we’re very focused on pharmaceutical interventions, technology, and biomarkers,” she says. “It shouldn’t be genetics and biomarkers and drugs or [mitigating] these risk factors. They need to come together.”

HANNAH ONGLEY: What led you to geriatric psychiatry?

KRISTINE YAFFE: I was always interested in the connections between the brain and behavior. I decided to go to medical school and had a really interesting time, but behavior, psychiatry, and psychology were barely taught. I was torn between neurology, psychiatry, and general medicine. I ended up doing neurology first and came to UCSF. I was around some of the smartest people I’ve ever met, but it was all about localizing the lesion with very little attention to what that might look like behaviorally. I found I wasn’t quite getting this connection to higher-level functioning, emotions, or cognition.

I tried to teach myself a lot. I was one of the only women residents in three years. At the last minute, I did a second residency in psychiatry. I didn’t think it was such a big leap. It was just a couple more years. It was my life, right? I was disowned by a lot of my neurology colleagues because they felt that I had crossed over. I was considered a good resident, capable. How could I do this soft thing?

HO: I’m interested in your trial on the epidemiology of Alzheimer’s and dementia and modifiable risk factors. Which behaviors were people most willing to focus on modifying?

KY: It’s hard to change people’s behavior. My thinking was maybe the answer was not to assign everybody the same thing. Maybe you tailor the intervention to risk factors and ask them what they want to work on and how they want to work on it. You might see more of a result, and it also might be motivating. This was all during COVID. It changed people’s behaviors. They’re shut up in their houses. They’re not seeing their friends. They’re not going to their doctors. They’re not exercising. They’re drinking too much. They’re not sleeping. I thought, Well, we’re never going to see anything! But, lo and behold, we did find something. I was shocked. Not only did we see a change in risk factors, which is good, but we also saw that their cognition got much better compared to the control.

HO: How did you assess cognitive activity?

KY: The idea is basically to use it or lose it. We applied it to both physical and cognitive [activity]. By being active, by stimulating your brain, you’re building resilience. There is also a big socioeconomic component. If you’re in utero and have better nutrition and medical care, and you’re raised in a more stimulating environment, you’re going to develop a bigger brain. I tell my patients, Find something where you’re learning. It could be reading. It could be learning a language. It could be games. It doesn’t matter what it is or how you’re doing it, as long as you’re challenging your brain.

Part of the challenge is that we’re very focused on pharmaceutical interventions, technology, and biomarkers. Let me be fully clear: I am a big fan of these things—I prescribe medications, I have a lot of work in biomarkers. But in the US, some of the lifestyle and modifiable risk factors have been short-changed because of the feeling that it’s soft, or not really getting at the issue. If you look closely, that’s not true. Some of these things have a very strong biological basis. Some of the most exciting work in the last few years has been showing the biological basis for risk factors and how they do modify biomarkers. We now need to look at what happens if we [use] drugs and replace. Do we get more results?

HO: Where are you noticing a shift among the next generation?

KY: One [junior colleague I’m working with] is interested in this question of genetics and risk factors. I think it’s very cutting-edge. We’re also very interested in what we call the “life course approach.” When in life does it make the most sense to look at these risk factors? Usually, when we study people, we’re studying them in their 70s and 80s. But we’ve missed out on the whole life before. When should you be exercising? We say often it’s never too early, and it’s never too late.