BY DALE BREDESEN, MD

Whether you are twenty-five or ninety-five, a high performance brain that is protected from neurodegeneration is one of your most valuable assets for lifelong cognitive health and well being.

Performance without protection is easy: cocaine, Adderall, and sugar can all give quick performance bursts at the expense of long-term protection.

Conversely, protection without performance is also easy: you could simply have your brain frozen in liquid nitrogen, where you’ll have no risk of neurodegeneration but likely won’t be pleased with your neural performance.

The real challenge—and opportunity—is achieving sustained cognitive health and performance with lifelong protection.

So how realistic is that, anyway?

To answer that, let’s first take a look at some real-life cognitive “guide stars”—individuals who’ve kept their minds thriving well into triple digits. Their stories not only inspire but also help us chart our own paths against what we now know is possible.

When Les Savino began his nearly daily workout at the age of sixty-one, he was already one of the oldest regulars at his gym in Hanover, Pennsylvania. Forty years later, his regular “lift day” at the gym included more than nine hundred reps on fifteen different machines. On aerobic fitness days, the former US Army Air Corps pilot and manufacturing executive would do eight miles on a stationary bicycle and two miles on a treadmill.

“Most people when they get older give up,” Les said in 2022.

“You know, it’s an effort to come in here every morning. That takes a lot of effort, and people don’t want to extend that effort. They just want to sit in a chair and watch television.”

But sitting around idle is not what Les wanted to do in his so-called “golden years.” And what struck many of the employees at the gym, as well as everyone else around him, was not just his ability to exercise for three hours each day at the age of one hundred, but his impeccable memory, astute wisdom, and acerbic wit.

Les, they observed, was not a man whose body and mind were drifting apart with age, but rather he was a person who was cognitively healthy at one hundred as most people in their thirties and forties.

Another shining example of cognitive vitality is neurologist Howard Tucker, MD, who was still seeing patients at Saint Vincent Charity Medical Center in Cleveland, Ohio, when he celebrated his 100th birthday. When the COVID-19 pandemic struck in his late nineties, Howard didn’t retreat like so many others his age were urged to do.

“I had to work,” he recalled.

“I put on a mask. The hospital didn’t tell me to stay home. They said everyone should come to work. In medicine, we have a responsibility. If you take it seriously, you follow through.”

When not at work, Howard and his wife—ten years his junior—often read the newspaper together in the morning, staying engaged with the latest news and the world around them. Howard is known for his ability to quote everyone from the statesman Winston Churchill to the poet Dorothy Parker, and he developed a thriving following on social media.

What I have come to adore about Howard is that he isn’t just using his remarkable cognitive health for himself, but in service to so many others.

Sisters Ruth Sweedler and Shirley Hodes also exemplify the power of lasting cognitive vitality. Both remained intellectually curious and socially engaged—two hallmarks of healthy longevity—into their second century.

“My doctor loves to talk to me,” the younger sister, Ruth, said in 2023.

“He’d say, ‘You’re amazing!’ And I’d say, ‘Because I’m old?’ And he’d say, ‘No! Because you’re sophisticated.’”

Three years older than Ruth, Shirley bristled at the very notion of age.

“I’m not old!” she said shortly after her 106th birthday, noting that no one who retained a curious mind was ever really old.

“Some people aren’t interested in anybody but themselves,” she said.

“I was always so interested in hearing people’s stories, backgrounds. They’re full of surprises!”

Cognitive guide stars like Ruth, Shirley, Howard, and Les are not alone. In 2024, there were approximately 750,000 centenarians worldwide—a number projected to quadruple over the next thirty years!

While not everyone who reaches one hundred will enjoy perfect cognitive health, we can take meaningful steps to improve our odds of approaching a hundred-year brain-span—marked by high-performance and protection against neurodegeneration. Let’s explore three practical strategies that can help get us there: physical exercise, mental exercise, and a gut-nourishing, brain-boosting diet.

1. Engage In Physical Exercise.

This information is intended for anyone between the ages of eighteen and 122. If you’re under eighteen, bookmark this section and check back in a few birthdays—you’re a little early for the data we’re about to explore. If you are older than 122, you don’t need to learn from me, more like I want to learn from you because you are doing a lot of things right.

Why is eighteen our starting point? A recent and rather surprising study found that a single Alzheimer’s risk gene variant—ApoE4, present in about twenty-five percent of the population—can impact memory as early as age eighteen.

Hard to believe, but true.

But here’s the good news: previous studies have shown that the memory effects of this gene variant can be offset by one particularly powerful antidote.

Here’s a hint: think Les Savino.

If you look at all the published evidence for enhancing cognition and preventing decline, the singular intervention that has the most evidence backing its efficacy is not some billion-dollar drug or expensive procedure. It’s exercise.

Aerobic Exercise

In the wake of World War II, a US Air Force exercise physiologist named Kenneth Cooper, MD, and a physical therapist named Colonel Pauline Potts, noticed something disconcerting among the young men they were charged with helping train.

Military recruits who appeared to be very fit—lean, muscular, and athletic—were often unable to engage in strenuous physical movement for longer than a few minutes.

This, they suspected, was because military training at that time emphasized short-duration over sustained drills. Together, Cooper and Potts conceived of a new kind of physical training—dubbed aerobics—designed to enhance the body’s ability to use oxygen efficiently and maintain endurance during prolonged activity.

Today, most people recognize aerobic exercise as a cornerstone of physical f itness—but far fewer realize its critical role in preserving and protecting cognitive health.

One of its most important benefits is enhanced oxygen delivery to the brain. Aerobic activity increases cerebral blood flow—the rate at which blood circulates through brain tissue, which at a very basic level means more oxygen.

This matters because, while the brain makes up only about two percent of total body weight, it consumes more than twenty percent of the body’s oxygen supply. Neurons are remarkably efficient at using oxygen—but they can’t store it. That means a steady, reliable flow is essential for maintaining focus, memory, and overall cognitive health.

However, recent research shows that this process becomes less efficient with age. Simply put, the aging brain doesn’t use oxygen as effectively as it once did. The aerobic solution to this problem is twofold:

First, aerobic exercise helps the brain maintain efficient oxygen use. Specifically, it improves vascular health—and healthier blood vessels are simply better at delivering oxygen and nutrients to the brain.

Second, aerobic exercise increases blood flow—even when vascular function begins to decline. This ensures that the brain continues to receive the oxygen it needs to function at its best, even under less-than-ideal conditions.

Strength Training

When healthy brain aging researcher Michael Valenzuela, PhD, led a small study involving 100 adults with mild cognitive impairment, he didn’t expect the results to be quite so striking.

Participants engaged in just ninety minutes of resistance exercise per week for six months—but the benefits extended well beyond the training period. Over the following year, Valenzuela and his team tracked participants using cognitive assessments and MRI scans targeting key regions of the hippocampus.

The findings were remarkable: strength training not only slowed brain shrinkage and improved cognitive performance, but those gains persisted for up to a full year after the program ended.

Valenzuela’s response was clear and emphatic. “Resistance exercise needs to become a standard part of dementia risk-reduction strategies,” he said in a 2020 statement from the University of Sydney.

Needs. That’s the word Valenzuela used. Not “should be considered” or “might be effective.” This intervention, he said, was an absolute must.

What makes this even more powerful is that strength training and aerobic exercise complement each other. Weights can be incorporated into an aerobic routine, allowing the brain to reap the combined benefits of enhanced oxygenation, neuroplasticity, and glymphatic clearance—a pseudo-lymphatic waste removal system that flushes out metabolic waste and other harmful substances from the brain.

So, whether you’re dancing, swimming, walking with dumbbells, or circuit training at the gym, movement is medicine. Just ask Les Savino, who kept his mind sharp well into his 100s. The prescription is simple: move your body to protect your brain.

2. Engage in Mental Exercise.

Think about how you start most mornings. Do you wake up in the same bed, in the same room, in the same house, in the same town? Do you shower in the same bathroom, using the same soap, drying off with the same towel?

If coffee is part of your morning ritual, is it brewed in the same machine, poured from the same cupboard, and sipped in the same familiar spot—or picked up from the same coffee shop on your way to work?

And speaking of work, do you take the same route each day, walking the same sidewalks or driving the same streets, watching the same scenery drift by as you commute?

There’s nothing inherently wrong with routine—most of us rely on it, and without it, daily life would feel chaotic and disorganized. But the predictability of these habits demands very little from the brain. In familiar environments, the neural pathways we formed years—or even decades—ago are more than enough to keep us functioning, often without much conscious effort.

This is why, in many cases, we begin to notice our struggles only when our environment changes. Once, a patient told me that she only began to worry about her cognitive health after her company changed locations.

Almost a year after the move, she still found herself driving to her old office on occasion. Another patient explained to me that he felt furious after his church moved to a fully digital tithing system. He knew his emotional response was irrational, but he just couldn’t get over the fact that, after decades of donating by check, he was going to have to learn how to do it a new way.

We used to think of situations like this as being related to people being “absent-minded” or “set in their ways.” We now know that there is a neurological explanation: They’ve formed deep and lasting connections in their brains for certain functions of life and, over the years, have gotten inadequate practice at forming new connections from day to day, month to month, and year to year.

This is where brain-training programs can offer valuable “plastic practice”—intentional opportunities to build and strengthen new neural connections. Now, we obviously can’t change everything about our lives every day, but I don’t think we need to. Instead, we should be striving to take on a small new cognitive health challenge each day, a medium new cognitive challenge each month, and a big new cognitive challenge each year.

Daily Cognitive Health Challenge

What counts as a small daily cognitive challenge? Just about anything that activates your memory, attention, decision-making, or problem-solving—especially if it nudges you to do something differently than usual.

For example, if you’re a habitual crossword puzzler, try switching things up with a cryptogram, solitaire, a word search, or sudoku. If you always visit the same coffee shop, opt for a different spot—and maybe even try a drink you’ve never had. If you work from the same desk each day, try setting up in a new location or shifting your start and end times to shake up your routine.

None of these changes need to become permanent habits—nor should they. The goal isn’t repetition, but disruption: brief, intentional breaks from routine that give your brain the chance to form new connections.

And once you’ve completed a particular daily challenge, it’s not off-limits going forward. In fact, revisiting a task after some time can be just as valuable, helping to reengage or even rebuild the neural pathways originally formed through that activity.

Monthly Cognitive Health Challenge

A medium-monthly cognitive challenge might involve reading a book from a genre you rarely explore, learning the rules of a new game or sport, or cooking meals from a cuisine that’s unfamiliar to you.

As with daily challenges, the goal isn’t just to try something new—but to vary the type of activity each month. For example, if one month you dive into the basics of Indian cooking, the next month, don’t just shift to another cuisine like Japanese—instead, take up backgammon.

The following month, skip another strategy game and try something entirely different, like immersing yourself in jazz. If you discover a love for sushi-making or develop an appreciation for Miles Davis, by all means, make them part of your life.

But remember—the objective isn’t mastery. It’s variety. It’s novelty. It’s about giving your brain the raw material it needs to build and strengthen new neural pathways.

Annual Cognitive Health Challenge

An annual cognitive challenge is, naturally, a bigger commitment—which is why it makes sense to align it with a meaningful personal goal or long-standing interest.

If a trip to Florence is on the horizon, enrolling in an Italian language course may be in order. If you’ve developed a love for the music of Miles Davis, perhaps this is the year to learn the trumpet or take up another instrument. True mastery of any subject after just a year is unlikely, but even ten to fifteen minutes a day of focused effort adds up.

After twelve months, you’ll have built not just skill, but a deeper cognitive capacity to engage with that passion for life.

3. Nourish Your Brain (and Gut).

In addition to physical and mental exercise, diet is an equally foundational pillar of brain health—especially through its influence on the gut microbiome.

This diverse inner ecosystem—made up of trillions of bacteria, fungi, viruses, and other microbes—does far more than support digestion. It plays a key role in keeping your brain sharp, resilient, and energized. Among its many functions, the gut microbiome:

• Synthesizes postbiotics—including microbially-derived B vitamins—which support neurotransmitter production, mental clarity, and overall brain health.

• Produces essential amino acids—the building blocks for brain-signaling molecules like dopamine and serotonin.

• Converts carbohydrates into energy, helping fuel both body and brain.

• Identifies and neutralizes toxins that enter through food and water—protecting against inflammation that can impair mental function.

• Enhances bioavailability of minerals like magnesium and zinc—essential cofactors for learning, memory, and stress resilience.

For these reasons, we need to nurture our microbiome and prioritize foods rich in probiotics and prebiotics—key ingredients for cultivating the ideal environment for postbiotics: the health-enhancing, brain-supportive compounds our microbes produce.

Let’s break down how each of these gut-health allies contributes to cognitive well being:

Probiotics. Found in fermented foods like kimchi, sauerkraut, sour pickles, miso, kombucha, and kefir, probiotics help cultivate a diverse and resilient community of gut microbes. A 2024 review in Neuroscience & Biobehavioral Reviews analyzed dozens of human and animal studies and found that regular consumption of fermented foods provides neuroprotective benefits and may even slow cognitive decline in older adults.

In one notable randomized, doubleblind and controlled trial, Alzheimer’s patients who drank a daily probiotic beverage for twelve weeks experienced measurable improvements in cognitive function, along with reduced markers of inflammation and oxidative stress.

These findings are echoed in a growing body of research, including a 2025 umbrella meta-analysis published in the Journal of Health, Population and Nutrition and a 2023 systematic review in Frontiers in Nutrition.

Both emphasize the antioxidant, anti-inflammatory, microbiome-balancing, and neuroprotective effects of fermented foods—highlighting their potential as targeted interventions for neurodegenerative conditions like Alzheimer’s disease and mild cognitive impairment.

Prebiotics. Garlic, onions, leeks, asparagus, bananas, apples, and legumes are rich sources of prebiotic fibers—nondigestible plant compounds that nourish the beneficial microbes already living in the gut. Research shows that diets rich in prebiotic fibers not only enhance gut health but also improve memory, lower stress-related hormones, and protect against inflammation that can compromise cognitive function.

In a 2024 randomized, placebo-controlled trial published in Nature Communications, thirty-six twin pairs over age sixty were assigned to receive either a prebiotic supplement (containing inulin and fructooligosaccharides) combined with protein, or placebo, for twelve weeks.

While both groups maintained similar muscle strength, the test group receiving the fiber supplement showed significantly better performance on cognitive tests—including reaction time, processing speed, and the Paired Associates Learning test, an early indicator of Alzheimer’s risk.

These gains reflect meaningful, real-life benefits—such as quicker responses while driving, better balance to prevent falls, and greater ability to maintain independence.

Expanding on this research, a 2023 study in Frontiers in Nutrition examined a combination pro-and prebiotic intake on the gut-brain connection. The findings suggest that synbiotics—the synergistic pairing of probiotics and prebiotics—can reduce neuroinflammation and increase levels of brain-derived neurotrophic factor (BDNF), a crucial protein for memory, learning, and neuroplasticity.

Postbiotics. When your diet provides enough pro-and prebiotics, your gut microbes can do what they do best: break down nutrients and produce beneficial postbiotics—compounds created by microbes during digestion. Among the most important are the B vitamins and vitamin K2—key to supporting memory, mental clarity, and overall cognitive health:

• Vitamin B1 (Thiamine): Essential for maintaining nerve health, thiamine supports optimal neuronal activity and neurotransmitter function. Deficiencies have been linked to cognitive disturbances, including poor memory, impaired attention, and increased risk of neurodegenerative conditions.

• Vitamin B6 (Pyridoxine): Plays a key role in the synthesis of neurotransmitters such as serotonin, dopamine, and GABA—chemicals critical for mood regulation and cognitive performance. Healthy B6 levels have been associated with enhanced memory, executive function, and reduced age-related cognitive health decline.

• Vitamin B9 (Folate): Copious research indicates folate plays a key role in decreasing homocysteine, improving vascular health, attenuating inflammation, and enhancing antioxidation—all of which lead to improved cognitive health.

• Vitamin B12 (Cobalamin): By raising cobalamin levels in individuals with early symptomatic cognitive impairment, researchers reported improvements in cognitive test scores in nearly seventy-five percent of participants—a striking finding, especially given that cobalamin deficiency affects approximately thirteen percent of US adults.

• Vitamin K2 (Menaquinone): Traditionally recognized for its role in blood clotting, menaquinone is increasingly being researched for its potential to reduce neuroinflammation and slow the progression of Alzheimer’s.

While these vitamins can be obtained through food and, when needed, supplements, many people struggle with proper absorption. This makes it all the more valuable that our gut microbes are capable of producing them as postbiotic byproducts.

Though the diet and exercise strategies we covered are not quick fixes, they are foundational habits that compound over time, rewiring the brain’s cognitive health for resilience, clarity, and longevity.

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Dale E Bredesen, MD, is internationally recognized as an expert in the mechanisms of neurodegenerative diseases such as Alzheimer’s. He graduated from Caltech, then earned his MD from Duke University Medical Center. He served as chief resident in neurology at the University of California, San Francisco, before joining Nobel laureate Stanley Prusiner’s laboratory at UCSF as an NIH postdoctoral fellow.

He is currently senior director of the Precision Brain Health program—the first program of its kind—at the Pacific Neuroscience Institute in Los Angeles.

Well Being Journal adapted the above excerpt from The Ageless Brain by Dale Bredesen, MD. Copyright © 2025 by Dale Bredesen and reprinted with permission from Flatiron Books.

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Bin Xiao, Lina Fu, Zhe Yang, Guran Yu. “Effect of probiotics on cognitive function and cardiovascular risk factors in mild cognitive impairment and Alzheimer’s disease: an umbrella meta-analysis,” J Health Popul Nutr. 2025 Apr 8;44(1):109.

Alexander Popescu, Monica German. “Vitamin K2 Holds Promise for Alzheimer’s Prevention and Treatment,” Nutrients. 2021 Jun 27;13(7):2206.

Anh Pham Thi Ngoc, Adil Zahoor, Dong Gyun Kim, et al. “Using Synbiotics as a Therapy to Protect Mental Health in Alzheimer’s Disease,” J Microbiol Biotechnol. 2024 Jun 21;34(9):1739–1747.

Elena Porras-García, Irene Fernández-Espada Calderón, et al. “Potential neuroprotective effects of fermented foods and beverages in old age: a systematic review,” Front Nutr. 2023 Jun 15;10:1170841.

Ramya Balasubramanian, Elizabeth Schneider, et al. “Fermented foods: Harnessing their potential to modulate the microbiota-gut-brain axis for mental health,” Neurosci Biobehav Rev. 2024 Mar:158:105562.

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