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Chipping Away at the Unknown: A Conversation with Dr. Yaakov Stern on Resilience, Research, and the Reality of Alzheimer’s

Jun 2, 2025 | For community

June is Alzheimer's & Brain Awareness Month. Flux Communications Committee Member Kahini Mehta, a PhD student at Columbia University, provided this interview with Dr. Yaakov Stern, chief of the Cognitive Neuroscience Division in the Department of Neurology, also at Columbia.

When Dr. Yaakov Stern began his career, Alzheimer's wasn’t widely understood. It wasn’t even called Alzheimer’s for most people. “My grandfather had what they called ‘senility,’” he recalls. “But people like Bob [Robert] Katzman were starting to shift the perception of Alzheimer’s as a rare inherited disorder to a prevalent disease.” Researchers were also beginning to highlight the role of proteins like tau and amyloid, which accumulate in the brains of individuals with Alzheimer’s disease.

As a graduate student, Dr. Stern worked closely with current Columbia Neurology leader, Dr. Richard Mayeux, at a time when the national institutes were just beginning to prioritize Alzheimer’s research. “It was a very new area, which is hard to imagine now. We didn’t know much, and everyone thought we’d find a treatment fast, maybe even a cure. I think we were influenced by Parkinson’s and the miracle of L-DOPA.”

But that quick miracle never came. “We know so much more now, across every level of science,” he says. Yet Alzheimer’s remains incredibly complex. It’s not just one disease: it’s multiple processes unfolding at once. That’s part of the challenge.

Despite the lack of a cure, recent advances have transformed the field. The ability to image pathology using PET scans (and now blood-based biomarkers) has opened whole new ways of tracking disease risk and progression. “That’s been a game changer,” he notes. We can now study cognitively normal individuals who already have amyloid, and ask why some decline and others don’t.

This question sits at the heart of his life’s work. Dr. Stern is best known for developing the concept of cognitive reserve, a framework for understanding why some people cope better with brain changes than others. “Some individuals seem to have more resilient networks,” he explains. “They function well even with the same amount of pathology as someone else who’s severely impaired.” The idea that some brains can take more of a hit than others has guided him for years.

He’s careful to point out that there’s no single formula for building cognitive reserve. “We started with IQ and education, but it’s much more than that. Different exposures seem to impart reserve in different ways.” Early-life exposures, socioeconomic background, quality of schooling, friendships, job complexity, exercise—every stage of life contributes.

Even defining Alzheimer’s remains a moving target. “Cognitive changes happen in normal aging. We see decreases in memory, processing speed, reasoning—but also gains in vocabulary and perspective.” When it comes to dementia, the key question seems to be: when do these changes start to impact daily function? “That varies a lot depending on someone’s lifestyle,” Dr. Stern admits. “You can’t diagnose someone the same way if they’re working at a high-stress law firm versus if they’re retired.”

There’s also tension in the shift toward pathology-based definitions. Most people don’t actively access advanced biomarker testing, and many people have amyloid in their brains but are cognitively normal. For Dr. Stern, this raises hard questions about when and how to diagnose, as well as who gets treatment.

He worries, too, about public messaging. “One challenge is that when you talk about lifestyle factors and reserve, people might feel guilt. Like they didn’t do enough if they get sick. I don’t know how common that is, but it’s something I think about. Still, I do think the public has a fairly accurate understanding of the disease these days. I just feel a lot of frustration that we’re not closer to a cure.”

He’s also frank about the recent controversies in the field. He acknowledges that there has been some disturbing fraud in the field, especially in amyloid research. But he also knows the field is broader than ever now. Omics, novel imaging techniques, and a more nuanced view of pathology are all expanding researchers’ horizons. Alzheimer’s research is no longer just about one protein.

Despite the challenges, Dr. Stern remains deeply committed. “There’s so much left to learn. I have brilliant postdocs doing work I never would have thought of, like combining amyloid PET with structural connectivity to better understand cognitive aging.” Dr. Stern believes the future lies in that kind of innovation.

For him, the fight is personal. “My grandfather had Alzheimer’s,” Dr. Stern reveals. So did his father. “I remember sitting with some of the best researchers in the world and realizing there was nothing we could do. It was devastating. The psychiatric symptoms especially. People still don’t talk about those enough,” Dr. Stern says.

But progress, he says, is still happening. Just in quieter, subtler ways. Researchers are still striving towards a deeper understanding, better tools, more nuance. “I don’t think there’s a single magic bullet. We chip away at the problem. That’s how we’ll get there.”

written by Kahini Mehta

written by Kahini Mehta

University of Pennsylvania

I am PhD student at Columbia University. While initially interested in journalism, I became drawn to neuroscience through the course of my education. I studied Psychology and English (non-fiction) at Brown University, where I grew increasingly interested in the brain-behavior interface.

I also developed a passion for computational approaches towards questions of abnormal behavior. As a result, I completed my undergraduate thesis on interventions targeting different cognitive mechanisms implicated in depression via a Drift Diffusion Model.

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