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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.”
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.
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.”
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.”
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.
Northwestern's SuperAgers research supports the University priority to advance the biosciences. Read more about the priorities.
Reader Responses
I am a psychology university student interested in keeping a healthy mind and body throughout my life. This article was fascinating and gives me hope for the future, both for myself and my/future generations. I am hoping that the ravages of diseases like Alzheimer's will become a thing of the past one day. I hope I live to see the day where growing old is something to be celebrated and not feared. Both my maternal and paternal grandmothers have lived into their mid-80s and still lead active lifestyles. So I've seen how the future can look for "superagers."
—Matthew San Francisco, via Northwestern Magazine
I am 86 years old and still full of life. I read a lot of Christian books and am currently doing an online Polish language course.
I was nothing special in my working career, a computer programmer, systems analyst, data communication techie. My dad was a bookbinder and paper cutter for his life. He died at the age of 60. My mom was a stay-at-home mom who died at age 34. I began Northwestern in the evenings in 1963, and because of good fortune and my faith I graduated in 1983.
My memory is really good. I can remember lots of movies and music of the '40s and '50s and more current.
I do think that one thing that provides long life is being silly with your spouse. I was married for 58 years. Another thing I believe about long life is keeping the mind active. I have read a lot of history and now I read a lot of Christian books. I also do play a lot of online chess.
I do thank Northwestern for the gift of learning subjects I would not have if it wasn't for those classes.
—Raymond Barkowski '83, Knoxville, Tenn., via Northwestern Magazine
I turn 92 next week. I think what kept me going so long is liking to learn new things. When I neared 70, I took a job teaching in China, which I did on and off from 2000 to 2008, sending letters to my hometown newspaper — letters that became part of a self-published book when I returned home. I also took calligraphy lessons, a form of intellectual tai chi. I like to credit olive oil for my health. Now I am working on my life experience for my grandchildren.
—Patricia Endress '54, '60 MS, Sherman, CT
I found reading about what happens to those donated brains was fascinating. And I like the Hebrew inscription on that wooden sign ("do not forsake me in my old age").
I am now 85. My entire career of work was as a Bacteriologist for the Illinois Department of Public Health. My husband (who was also a Bacteriologist: we met at work) and I never had children, but traveled worldwide; mostly into areas of wilderness. We also kept quite active doing backpacking, x-c skiing, bicycling, hiking, and folk dancing.. He died at 92 of Alzheimer's and dementia. I now live in independent living at a Senior Living facility; where I still try to stay very active physically and mentally.
—Mary Ellen Endo South Elgin, Ill.
The brain that Tamar Gefen was holding could have been [the brain of] my father, Dr. William “Wiley” Rosenberg, a pioneering Chicago ophthalmologist who died in September 2018 at the age of 101. He was a participant in that study and agreed to donate his brain. When they opened his skull, the researchers may have been surprised by its tint of Northwestern Purple. My Dad, near the near the end of his six decades of private medical practice sold his practice to Northwestern’s Feinberg School of Medicine, where he practiced for several more years before his retirement. But that’s not all. His oldest son, Dr. Michael A. Rosenberg ’67 MD, recently retired as professor emeritus from the Department of Ophthalmology at the very same school, and his youngest daughter, Dr. Lisa F. Rosenberg ’89 GME, is a clinical associate professor of ophthalmology at Feinberg. His son-in-law, Fredric J. Kreiter ’72 JD, is a graduate of the Northwestern Pritzker School of Law.
Oh and me? Class of 1967 from the then–Medill School of Journalism.
—Neil D. Rosenberg '67 MS, Tamarac, Fla.
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