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Doctor explores lifestyle approach to dementia prevention

May 7, 2017

Dr Richard Isaacson is the first to admit that he is a terrible cook.

The Cornell neurologist, a dementia expert, is more of a takeout guy—but a takeout guy with enviable discipline when browsing a restaurant menu. Faced with minimally effective treatments at best and a recent trail of disappointing drug trials, Isaacson is among a growing cadre of doctors turning to lifestyle interventions to prevent or slow the onset of Alzheimer’s disease. And nutrition, he feels, can be integral in doing so, particularly in people like himself with a family history of the disease.

Isaacson founded the Alzheimer’s Prevention Clinic at Weill Cornell Medicine and NewYork-Presbyterian in 2013. It was the first medical center in the country, and perhaps the world, dedicated to dementia prevention as opposed to just management. The clinic’s mission is to catch people at risk for Alzheimer’s years before symptoms would normally arise and to intervene with personalized prevention approaches. By analyzing and addressing a complicated tangle of family history, biomarkers, and lifestyle factors that may predict an increased risk, Isaacson is seeing real results.

The clinic is housed in a slender building tucked away between a bodega and an apartment building on New York City’s Upper East Side. I arrive around 9:30 on a chilly Thursday morning in March, after an eternally delayed subway ride. A few minutes later, Isaacson strides in.

“How was your commute?” I ask.

“Quick,” he answers with a muted New York accent and a grin. “I chose hospital housing, and my apartment is as close as you can possibly get to the clinic.”

We shed our coats and sit down in his consultation room. “Look at this,” he beams, pointing to his computer screen. A recent patient lab report reveals a complex breakdown of cholesterol subtypes—and also insulin levels, adiponectin levels, and hemoglobin A1c status. It seems more the health record of a cardiology patient, not of someone being seen by a dementia neurologist.

Dr Isaacson walks us through his typical patient assessment.
Photo by Darbe Rotach

Like heart disease, neurodegeneration typically doesn’t surface overnight. Pathologic changes in the brain can begin 20 or 30 years before Alzheimer’s becomes symptomatic. Roughly 400 of Isaacson’s 600 clinic patients are seen exclusively for prevention, the majority of whom have no symptoms at all. “A lot of my patients are in their 30s and 40s, and my youngest is actually 27,” he says. “But I’ll admit that any younger than that, and I’m not quite sure what to do.”

When Isaacson isn’t traveling to lecture, overseeing a residency program, or visiting his fiancé, an ophthalmology resident in Los Angeles, he is usually seeing patients. He starts by screening them for dozens of risk factors associated with Alzheimer’s dementia: Impaired glucose metabolism, excess visceral fat, inflammation, and elevated homocysteine are just a few.

Some associations have not necessarily been widely reported on in the literature. For example, Isaacson has observed that small, dense low-density lipoprotein cholesterol particles—known to be proinflammatory—are associated with impaired executive function. He now often orders cholesterol fractionation testing on his patients.

A patient health record reveals cholesterol fractionation testing results.
Photo by Darbe Rotach

“I’m a clinician first, and I see patterns,” he says. “It only takes 20 or so patients to say, ‘Hey, your executive function is impaired, and your particle size is worrisome. Maybe we should try cholesterol modification.'” Isaacson is, however, launching a pilot trial exploring the link between cholesterol subtypes and dementia risk; and plenty if not most of the interventions he considers are evidence-based—interventions like exercise, improving sleep health, encouraging socializing, and treating hyperinsulinemia.

He is also a big proponent of Mediterranean-like diets in helping fend off Alzheimer’s. A growing body of observational data links diets centered around healthy fats, vegetables, and whole grains with improved brain health, especially when combined with other lifestyle factors.

Isaacson cites the FINGER trial,[1] published in the Lancet in 2015. This large, 2-year study found that a combined regimen of a brain-healthy diet, exercise, cognitive training, and vascular risk monitoring helps improve or maintain cognitive functioning in elderly people at risk for Alzheimer’s. Similarly, preliminary data from the MAPT trial[2] suggest that supplementation with the omega-3 fatty acid docosahexaenoic acid—or DHA—combined with cognitive interventions and exercise for 3 years can improve cognition.

But then there are the unmodifiable Alzheimer’s risk factors to consider, namely family history and our genomic luck of the draw.

A year or so ago, Isaacson began suggesting that his patients undergo gene sequencing and share their results. He first looks for variants of the APOE gene that are known to increase Alzheimer’s risk, including the APOE4 allele, which is carried by around 20% of people. Having one copy of APOE4 can double Alzheimer’s risk; having two results in a 12-fold increased risk.

Isaacson also screens for a bevy of less common genes associated with many forms of dementia. When taken together with clinical and lifestyle risk factors, he can come up with an overall risk profile for each patient and better customize care. Research[3] by Isaacson and colleagues presented at last year’s Clinical Trials on Alzheimer’s Disease meeting shows that the effectiveness of certain prevention interventions is greatly influenced by each patient’s genetic profile.

“We’re figuring out how all these genes and factors interact together to influence the chances of getting Alzheimer’s. Then we can more accurately determine which interventions might work in which patients,” he explains while calling up another patient report. “She has a mutation in the TNF gene that can increase risk—up to 6.6-fold if she also has APOE4. Should I be treating her with an anti-TNF drug or an anti-inflammatory? Maybe. This is the kind of thing we’re trying to figure out.”

A Kid From Long Island

Dr Isaacson playing cello as a child.
Photo courtesy of Dr Richard Isaacson

Isaacson grew up in Commack, Long Island, a town of 40,000 people 50 miles east of New York City. He collected baseball cards. He played cello and bass guitar. He built a recording studio in his childhood basement. And he was dead-set on being a doctor from an early age.

After graduating from Commack High School—where he was recently named an alumni of distinction and where his photo hangs alongside those of fellow recipients Rosie O’Donnell and Bob Costas—he was accepted into a combined undergraduate/MD program at the University of Missouri in Kansas City. At the time, it was one of the only programs of its kind in the country.

“I got my white coat at 17 years old and basically finished undergrad at 19 and medical school at 23,” he recalls—not quite Doogie Howser numbers but impressive.

His family having fled the New York winters for Boca Raton, Isaacson did his internship at the University of Miami before heading to Beth Israel Deaconess Medical Center and Harvard Medical School for his residency. He knew early on that he was headed for a career in neurology. “I was fascinated by the brain, and I have a pretty significant family history of Alzheimer’s,” he reveals. “My uncle was diagnosed when I was in high school, and I’ve had four family members diagnosed overall.”

After residency, Isaacson returned to Florida to practice and ultimately landed a professorship at the University of Miami Miller School of Medicine. It was here, over 10 years ago, that he encountered the patient who would change his career course for good. The man was a retired surgeon beginning to have memory problems. After cornering Isaacson in the hallway, the two spent 40 minutes talking about what, if anything, can be done to prevent or slow Alzheimer disease.

“He said, ‘You have a family history. What do you do? What can I do?,'” Isaacson recalls. “You know how surgeons are; they mean business. So I told him.” Isaacson mentioned early data on omega-3 fatty acids and exercise. “It was my first prevention consult.”

Somewhat serendipitously, 1 week later, Isaacson received a second prevention consult. It was from his cardiologist colleague Dr Arthur Agatston, creator of the wildly successful South Beach diet and one of the first preventive cardiologists in the country. (Agatston also developed the now commonly used Agatston calcium score.)

“The patient had so many metabolic abnormalities, and I couldn’t help but think they were somehow related to his memory problems,” Isaacson remembers. “I thought, ‘This is what I should be doing,’ and over the next few years my practice went from 100% Alzheimer’s treatment to well over 25% prevention.”

In 2012, after finishing a research project, Isaacson treated his collaborators, including NewYork-Presbyterian neurologist Dr Joe Safdieh, to Yankees tickets. “Great game. They won. While we there, Joe leaned over and said, ‘You know, we’re hiring, and we’re the official hospital of the New York Yankees.'” That led to an interview, and Isaacson was headed north.

428 East 72nd Street, home of the Alzheimer’s Prevention Clinic at Weill Cornell Medicine and NewYork-Presbyterian.
Photo by Darbe Rotach

Getting an Alzheimer’s prevention clinic off the ground, however, was easier said than done.

“When the dean found out the name of this crazy clinic I wanted to start, she was like, ‘I don’t know. I have to meet with this guy,'” Isaacson jokes. “I had 15 minutes to pitch her, and I had my talking points. She definitely wasn’t expecting someone like me—I think she thought I’d be older; more of a gray-bearded neurologist type.” She was expecting Oliver Sacks.

The dean was skeptical but ultimately sold.

A Chance Encounter

Stephen Chambers’ father was diagnosed with Alzheimer’s a little over 2 years ago. Prior to that, his grandmother and uncle had also developed the disease. Now, the 45-year-old New York physical therapist is hoping that by eating right, living right, and keeping tabs on his health, he can reduce his own Alzheimer’s risk.

After hearing the news about his dad, Chambers and his wife began doing advocacy work with the Alzheimer’s Association of New York. In late 2015, Isaacson gave a seminar to the group about reducing dementia risk early in life.

“I was actually stuck at work and unable to attend, but my wife went,” Chambers tells me in an email. “She came home with Dr I’s book and said, ‘You have to go see this guy!’ I called the next day to schedule an appointment.”

Chambers now regularly checks in with Isaacson and is enlightened by what he’s learned.

“Being a healthcare professional, I walked in with a pretty good understanding of nutrition and metabolism…and I had viewed this disease as something that we couldn’t do anything about,” he recalls. “However, once we sat down and reviewed all of the data, including my DNA test results, blood analysis, and cognitive function testing, we were able to put all the information together like pieces of a puzzle. I learned we can make adjustments to our diet and lifestyle and minimize the risk of getting the disease.”

Dr Isaacson shows Medscape around his clinic.
Photo by Darbe Rotach

Isaacson’s former colleague Dorene M. Rentz, PsyD, an associate professor of neurology at Harvard Medical School, adds, “I applaud Dr Richard Isaacson’s vision for providing hope, education, and medical care to at-risk individuals and his willingness to test these novel prevention therapies with scientific rigor.”

Since Isaacson’s clinic opened in 2013 (and later expanded to Puerto Rico), other Alzheimer’s prevention clinics have opened around the country. However, Cornell’s is certainly among the most well-known, in part due to a chance celebrity encounter.

Dr Isaacson and Maria Shriver filming a Medscape commentary in 2016.
Photo courtesy of Medscape

While Isaacson was filming a news segment alongside journalist and Alzheimer’s advocate Maria Shriver, the two struck up a conversation. Shriver’s father, Sargent, was diagnosed with Alzheimer’s in his 80s; she was curious what steps she could take to avoid or delay the disorder and began collaborating with Isaacson. They have since worked on a number of advocacy and outreach projects intended to educate doctors and patients on Alzheimer’s prevention.

“It certainly added a Hollywood contingent to my practice,” he admits. “But having some degree of high-profile patients has really helped us. It’s hard to get funding for the work we do through NIH. We rely a lot on philanthropy.”

Isaacson now sees a number of other well-to-do patients, from entertainers to CEOs of every ilk; most of whom, he says, made appointments and waited 6 months to get in like everyone else. “I don’t really get star struck sitting across from a TV star,” he says. “But if it was a Yankee, I probably would. If Derek Jeter walked in here, I’d get flustered.”

Isaacson has never been a believer in the idea that Alzheimer’s disease is exclusively due to amyloid and tau protein build-up in the brain, as many have speculated over the years. But he does think that biomedical science will soon have some answers. He believes there’s something to the idea that mitochondrial dysfunction and inflammation might contribute to cognitive decline. He’s also excited to see how insulin-based therapies perform in clinical trials.

“I don’t think Alzheimer’s is the same for everyone. I think there are many roads to getting the disease, and hopefully we can figure out how to treat it once it arises,” he says. But for now, it appears that mitigating risk is our best bet.

In the interest of reducing his own risk for Alzheimer’s, Isaacson has a vigilant daily routine. Except for the cocoa powder and hint of sugar he puts in his coffee, he typically fasts until the afternoon to keep his insulin down. He is an avid jogger, a spinning class regular, and takes his dog on long daily walks. (His guilty pleasure, the smartphone game sensation Pokémon Go, lets him know when he’s reached half an hour.)

Playing Pokémon Go in the clinic hallway.
Photo courtesy of Darbe Rotach

Isaacson eats primarily take out, yet his diet couldn’t be healthier. Witness his postexercise usual: “I always get the same thing. I’ll start with a fresh coconut for potassium. Then I’ll get an acai bowl with three scoops of complete plant protein, blueberries, and kale.” He also eats a lot of salmon, whole grains, and occasionally chicken.

He does allow himself red meat once or so a week, and the previous day he had indulged at Jackson Hole, a well-known Manhattan burger spot—though he got his with avocado and without the bun.

“So you really don’t cook much, huh?” I ask Isaacson before leaving his clinic.

“Almost never,” he admits. “The last time I remember cooking was during internship. Everything started smoking and that was it. I ended up storing my textbooks in the oven because I wasn’t using it. No joke.”


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