Northwestern researchers study brains to better understand memory, aging and the human spirit. By Martin Wilson
It’s a strange experience to hold a human brain in your hands. The mass of spongy tissue — home to all our thoughts and memories — is a little smaller than a football and weighs about as much as a half-gallon of milk. Yet its worth is immeasurable.
“I don’t know how to describe the feeling of holding the brain of someone you’ve known,” says Tamar Gefen. “It’s intense. There is a sense of overwhelming respect and honor because, my God, this is their most precious donation.”
On a quest to end the scourge of neurodegenerative disease, Gefen hopes brains like the one she’s holding — donated by generous and passionate research participants — will reveal the secrets to understanding memory and aging. Gefen ’12 MS, ’15 PhD is a clinical neuropsychologist at the Mesulam Center for Cognitive Neurology and Alzheimer’s Disease in Northwestern’s Feinberg School of Medicine. She helps lead the center’s SuperAging Program, which studies older individuals with exceptional memories. “We’re flipping the ethos of aging on its head,” Gefen says.
Today, the Mesulam Center brings together physicians, scientists, social workers and others to study the brain and all the various challenges that can come with aging — working to uncover clues that will help us understand, treat and prevent dementia.
It’s a big brain place.
And Gefen is one of the most promising brains on the case. In person, she combines the focused energy of an ER doctor with the soulful intensity of a therapist. As she talks about her work, she maintains an urgent and steady gaze, even as her eyes occasionally glisten with emotion.
She sees the critical need for advances in neurological care as she works every day with individuals dealing with a wide range of dementias or cognitive decline. Alzheimer’s disease is the most common cause of dementia for people over 65 — an estimated 6.9 million Americans are living with Alzheimer’s in 2024.
“There’s no question they need help,” Gefen says. “They need a cure. I need a cure. We all need to work harder and faster.”
Sel Erder Yackley was born during an earthquake in Istanbul in December 1939. And 84 years later — wearing a colorful, feathered scarf while bustling around her Chicago apartment — she retains her flair for the dramatic.
Yackley grew up in a multilingual household: While the family spoke Turkish, her mechanical engineer father learned German, and her mother spoke French. To keep pace, Yackley attended a special school in Ankara, Turkey’s capital, to learn English.
After graduating high school, she won a scholarship to attend Arizona State University in Tempe, Ariz.
“I thought I would become a psychologist,” Yackley remembers. “But the only C I got was in psychology. Everything else was A’s and B’s, so I decided psychology is not for me!”
She turned her attention to journalism and received another scholarship, this time to attend Northwestern in what is now the Medill School of Journalism, Media, Integrated Marketing Communications.
Yackley earned her master’s degree in journalism and immediately landed a broadcast wire gig with United Press International, adapting written articles to be transmitted over the radio.
After three years, she heard about a job at The Chicago Tribune. There was just one problem. “I always considered myself a liberal,” she says. “And in my mind, The Chicago Tribune was way too conservative. I didn’t think I would want to work there.”
Despite her doubts, Yackley worked in neighborhood news for the Tribune, where she sat across from a “troublemaking” reporter, the late Michael Killian. Even within the “conservative” Tribune, Yackley too found ways to make some trouble. She remembers writing a series of articles in the 1960s about several of Chicago’s south suburbs that were successfully desegregating their public schools.
“I won an award for that,” Yackley says. When a parent’s club in Arlington Heights, a predominantly white northwest suburb of Chicago, invited her to speak, “I didn’t get booed, but I didn’t get any applause either.”
Today, Yackley credits her SuperAger status partially to her upbringing in a multilingual household and her active lifestyle. She serves on the board of the Turkish-American Women’s Scholarship Fund, knits hats for people experiencing homelessness and published a memoir in 2006.
Her participation in the SuperAging Program continues her family’s longtime connection with the University. “All three of my children went to Northwestern to get their bachelor’s degrees. I’m very proud,” Yackley beams. “Northwestern was a second home to all of us.”
There’s no such thing as a “typical” SuperAger. They are not a monolithic group of joggers or teetotalers or churchgoers. Some are globetrotting jokesters; some are quiet homebodies. Some eat acai; some eat Snickers. But all have cognitive abilities that defy the odds of aging.
For research purposes, a SuperAger is defined as someone who is over age 80 but has the memory capacity of someone in their 50s or 60s and “sometimes even younger than that,” says Gefen.
The study, now in its 25th year, has about 110 active participants, the majority of whom have agreed to donate their brains to the program after their death. “We have about 70 donated brains,” says Gefen. “That’s incredible.”
Every year, Gefen and her team meet with each SuperAger to test their memory, language, executive functioning, visuospatial functioning and more. Researchers also take MRIs of each participant’s brain and collect blood samples to track longitudinal changes. “We’re trying to find a biomarker for successful aging,” says Gefen. Some of the participants in the program have been doing this for decades.
But the way to identify a SuperAger in the first place is less high tech: Gefen typically employs paper-and-pencil tests. During these tests, researchers may read a list of 15 words several times to a participant. Then 30 minutes later, they ask the participant to repeat back those words. Gefen says that a typical ager, around 50 years old, would likely remember eight or nine words. But SuperAgers often remember 14 or 15 words, year after year. “I’m almost 40,” Gefen says, laughing, “and I can’t really see myself remembering that much.”
Once enrolled at age 80, participants remain in the program regardless of their annual test performance or their physical fitness. “We can’t predict what’s going to happen, so part of this study is to evaluate the trajectories of aging,” she says. “Many SuperAgers retain their cognitive stability over time.”
Gefen says SuperAgers seem to share some other common traits. “We have shown preliminarily that SuperAgers tend to be more extroverted and less neurotic, based on personality tests,” says Gefen. “We are studying diet. I’m curious about differences in religious proclivity and ethnicity, and one of my students wants to examine their tendencies toward demonstrating grit, will power and tenacity.”
Gefen says the SuperAging Program is arguably the most comprehensive study of successful aging. “It allows for the understanding of cognition, of biomarkers, of anatomy and of pathology at death,” she says. “A SuperAging study of this caliber is unique to Northwestern.”
One of the key differentiators of the program is the sheer length of time the researchers have been tracking their volunteer participants — in some cases for more than 20 years. Another differentiator is the center’s collection of donated brains.
Tamar Gefen
Each brain is carefully tracked and dissected. The dissected brains are then stored, suspended in a fixative solution, in refrigeration units and freezers. Impossibly thin cross-sections are sliced for slides and stained, allowing researchers to see the neurons clearly. Every slide is stored for efficient retrieval in what looks like a card catalog from an old-school library.
“I’m able to study these SuperAgers during life and then study their brains after death,” Gefen says. “The bridge between meeting these individuals, getting close to many of them, and then feeling that same sense of intimacy even after they pass is, for me, not just scientific. There’s a spiritual element too.”
Gefen recalls one SuperAger in particular — memorable both because she was a Holocaust survivor and because she once tried to set Gefen up with her grandson. “She was very happy and resilient,” Gefen remembers. “And she was funny! It’s been over 10 years, but I still think about her all the time. I still examine her brain.
“Her hippocampus was beautiful,” she continues. “The architecture was well-defined. Her neurons were plump and healthy. I remember thinking how incredible it was that such a stunning and intricate structure could hold such terrible memories — how it managed to withstand a lifetime of experience, good and bad.”
And that’s just a single brain, known in life and examined after death. That same kind of connection and potential for discovery exists in each brain within the collection — each an entire world, and collectively rich with beauty, possibility and mystery.
“There is a sense of immortality in brain donation,” Gefen says. “We will be utilizing this person’s tissue for decades to come. If there is a cure to Alzheimer’s disease, if there is a cure to neurodegeneration, it’s somewhere in those brains. So is that person gone entirely?”
She leans forward and smiles. “They’re still contributing.”
Gefen half-jokingly worries that people might think the amount of time she spends with brains is “creepy.” But the Mesulam Center collection offers special, nearly limitless research opportunities.
Recent studies show that SuperAger brains are physically different from other brains. Gefen and her team have found that neurons in the hippocampus of a SuperAger brain are bigger and plumper than in the brains of their cognitively average peers and even in the brains of much younger individuals. Further, SuperAgers appear to have lower amounts of the protein tau in their blood compared with their cognitively average peers. Tangles of tau in the brain are characteristic of Alzheimer’s disease.
SuperAgers also have more von Economo neurons (VENs) in the anterior cingulate cortex — an area of the brain responsible for encoding memories — than some people in their 20s and 30s.
“And for reasons we’re still trying to figure out,” says Gefen, “in SuperAgers, the VENs were packed in and lined up like sardines in a can — tons of them.
“Down the line, we need to understand what makes those neurons special. In SuperAgers, why are they resilient to disease? Are they enhancing efficient processing of information? We’re working systematically to answer all those questions.”
Beyond the published findings and dogged investigation, the research is also personal.
Many of the researchers and scientists at the center have family histories of neurodegenerative disease, including Gefen.
“My grandmother was diagnosed with Alzheimer’s disease at a relatively young age. I was young, but it still left a mark,” she says. “Sometimes in the lab we joke that it’s me-search instead of research. It’s only a little bit funny. But the personal connection drives a lot of our hard work and dedication. It’s not just about our participants. It’s our family. It’s everyone around us. We’re not necessarily spared.”
Ralph Rehbock was born in Gotha, Germany, in 1934.
His earliest memories are of a normal childhood, but historical events had already shaped his future before he was even a year old. In 1935 the passage of the Nuremburg Laws stripped German Jews, including his parents, of their citizenship. Rehbock’s mother, Ruth, became convinced the family needed to flee.
Fortunately, Ruth was able to obtain sponsorship from cousins she had never met who were living in Chicago.
“We got a letter in the summer of 1938 saying that we should appear at the American Embassy on the 10th of November,” says Rehbock. “We got to Berlin on the 8th because we didn’t want to be late for the appointment. The night of the 9th we looked out of the hotel room window and there were flames.”
It was Kristallnacht — the “night of broken glass” — when German forces attacked and vandalized Jewish-owned businesses, schools, homes and synagogues.
Some 30,000 German Jews were arrested that night. The Rehbocks never returned to Gotha.
They sailed on the SS Manhattan to New York Harbor in 1938 and eventually settled in Chicago’s Hyde Park neighborhood.
In 1948, in his first science class at Hyde Park High School, Rehbock met his future wife, Enid Solomon ’56. Both graduated from Northwestern — Rehbock in 1957 with a degree in industrial engineering and Solomon in 1956 with a degree in speech therapy. They married in 1956 and had two children, Mark and Robert. Today they have been married for 68 years and have eight grandchildren and five great-grandchildren.
Rehbock served in the U.S. Air Force during the Korean War and retired a few years ago after working as a manufacturers’ sales rep in the gift industry.
Rehbock says he is happy to be a part of the SuperAging Program.
“We, as Holocaust survivors, need to have our stories remembered,” says Rehbock, who shares the story of his narrow escape from the Nazis with students who visit the Illinois Holocaust Museum.
“When I speak, I ask everyone in the class to go home, get their parents or grandparents together, get out their recording instrument and ask them questions about their lives,” Rehbock continues. “We SuperAgers go to funerals all too often, and grandparents are gone, and there’s a hole in the background.
“That’s why storytelling is so important. Life stories should not be lost and forgotten.”
The SuperAgers program started 25 years ago as the brainchild of Marsel Mesulam, founding director of the internationally renowned Northwestern University Cognitive Neurology and Alzheimer’s Disease Center, which was later renamed in his honor. Mesulam may be best known for his pioneering research in primary progressive aphasia, a form of dementia that affects language and speech.
In January 2023 Mesulam stepped down, turning the reins over to Robert Vassar, the Davee Professor of Alzheimer Research in Feinberg. A molecular geneticist by training, Vassar is another scientist fueled by personal passion: Experiencing his mother’s Alzheimer’s diagnosis in 1983 set him on his current research path.
Vassar believes that multidisciplinary collaboration — a hallmark of the center since its inception — is the “secret sauce.”
“Mesulam’s idea was to bring researchers, graduate students and staff investigating all aspects of aging and dementia together under one roof,” says Vassar, “to study everything from the gene and the molecule all the way up to the person and society.”
The Mesulam Center convenes monthly “clinical-pathological correlation meetings,” which bring together the entire team to connect patients’ symptoms to their neuropathology — that is, to understand what is actually happening inside each patient’s brain. “You can see it all pulled together,” Vassar says.
Other big thinkers around the center agree with and echo the center’s motto — “from cells to social work.”
Tamar Gefen, left, observes as Allegra Kawles points to an image of neurons and neuropathology while incoming doctoral student Antonia Zouridakis looks on.
Allegra Kawles ’20 came to work at the center first as a volunteer research assistant after her junior year as a neurobiology major in Northwestern’s Weinberg College of Arts and Sciences and now as a second-year doctoral student in Feinberg.
“You have so many eyes on SuperAger research participants at every stage,” Kawles says. “The social workers and the research assistants know them. The neurologists and psychologists know them. And then when it comes to an autopsy, the neuropathologist and the research staff know them in another way. There’s just so much care being put into each person.”
Molly Mather believes this approach makes an enormous difference.
Mather is a clinical co-lead of the program and a clinical neuropsychologist who treats patients with issues related to thinking, such as memory or language problems. She says clinicians who work with people experiencing cognitive decline and dementia often take a “best guess” approach to diagnosis, but her position allows for better insights.
“Working at the Mesulam Center — with a brain bank, doing brain research — has allowed me to grasp nuances of brain aging with a depth that would not be possible otherwise,” Mather says. “It can often take years for new findings about the brain to trickle down to clinical practice. This type of multidisciplinary research center shortens the path from discovery to impact.”
Gefen and Vassar are excited about their progress and the future of their work.
“We’re finally, as a field, making progress with treatments for Alzheimer’s,” Vassar says. “The first disease-modifying therapies for Alzheimer’s disease have been approved by the U.S. Food and Drug Administration. … We’re part of a clinical trial that is using these drugs as a prevention strategy. It’s a long trial … but it’s really exciting.
“We still have to think of other therapies that attack different aspects of the disease. … But someday we’ll have a toolkit with a number of different therapies to individually treat people on a personalized level.”
For her part, Gefen wants to make progress toward scientific and clinical breakthroughs. But she also wants to challenge every brain — even young and healthy ones — to think differently about aging.
“I want to break the assumption that old age is synonymous with intellectual decline. I want people to understand that aging can be good,” she says, sitting in her downtown Chicago office.
“And I want people to understand the dedication of our donor participants to brain science, to trying to solve Alzheimer’s disease, so much so that they are willing to hand over their brains so that we at Northwestern can make a discovery.”
Above her desk there’s an intricately painted wooden sign in Hebrew.
“That sign was made for me by a SuperAger,” Gefen explains. “He’s an artist, and he asked me for my favorite quote. The quote [from Psalms] says, ‘Do not forsake me in my old age.’ It can mean exactly what it says: ‘In my old age, don’t cast me away, take care of me.’ The second, more hidden meaning can be a person speaking to their own mind: ‘Don’t forsake me in my old age.’ ”
It reminds her that her work is critical — and intimate. “My job entails working with life and death,” she says. “It’s a study of aging, time, humanity. And I’m hopeful. I have a family history of Alzheimer’s disease. Understandably, I’m nervous. My family is nervous. But SuperAgers offer hope that there’s a path.”
Martin Wilson ’10 MS is director of creative production in Northwestern’s Office of Global Marketing and Communications. Yes, he held a brain while reporting this story.
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