- [Announcer] "Your Fantastic Mind" brought to you in part by Sarah and Jim Kennedy.

(exciting music) (exciting music continues) (exciting music fades) - Welcome to "Your Fantastic Mind."

I'm Jaye Watson.

And we begin this week at the home of one of the world's great wonders, the Taj Mahal in Agra, India.

This is a country where ancient history and modern innovation lives side by side.

It is also home to one of the most ambitious health studies ever attempted.

For 15 years, the CARRS study has followed over 30,000 people to understand why chronic health risk factors such as high blood sugar, blood pressure, cholesterol, lifestyle, and genetics lead to heart disease, stroke, and type 2 diabetes.

Well now, researchers are turning to the brain to uncover why these same risk factors accelerate cognitive decline and what they're learning will have a global impact.

(gentle music) It is unlike anywhere else in the world.

(majestic music) Home to more than 1.4 billion people and hundreds of languages.

(people speaking foreign language) India's richness comes from an extraordinary diversity.

(rider speaking foreign language) - [Jaye] Of culture, cuisine, and community, and from the ongoing coexistence of profound differences.

- One of the ways in which India is similar to the United States is you could see it as a melting pot.

- A meeting place of cultures, a meeting place of genes, a meeting place of opinions, ideas.

- So there is this tapestry of culture, language, genes, lifestyle that kind of is very unique in this place.

- [Shivani] People are very interested in maintaining their traditions, but they're also very open to evolving traditions.

- Hi.

- [Jaye] But there's something else.

In India, people are developing diabetes and heart disease nearly a decade earlier than in the West.

- We tend to get type 2 diabetes 10 years earlier than seen in a white European population.

- In terms of heart attacks, Indians have more completed heart attacks as compared to the Western populations.

- [Jaye] Doctors are also seeing dementia appearing earlier too.

- They develop dementia 10 years earlier.

They're diagnosed later in their own disease.

- So we know that the shared risk factors for cardiovascular disease and diabetes somehow are linked to the risk of Alzheimer's disease, and yet we don't know how.

- [Jaye] These conditions don't arrive suddenly.

They don't begin with memory loss, stroke, or heart attack.

They build quietly over years, even decades, long before symptoms appear.

To understand how this happens, scientists are doing something unique.

For 15 years, they've been following over 20,000 people age 20 and older through their lives, returning year after year watching their health change in real time.

The CARRS study began in 2010 by tracking diabetes, blood pressure, and cholesterol, key drivers of cardiometabolic disease.

Those conditions are recognized as risk factors for Alzheimer's disease.

In 2024, Emory's Goizueta Brain Health Institute joined CARRS to bring the brain into the picture.

But before we look ahead, we need to look back at how this landmark study began.

- I got into serious diabetes research in 1992 working at the NIH for four years with the famous Pima Indian study which has been going on in the United States since the early 1960s.

- [Jaye] Dr.

Venkat Narayan is a renowned diabetologist and head of the Emory Global Diabetes Research Center.

Early in his career, Dr.

Narayan studied the Pima Indians of Arizona.

A population that had some of the highest rates of diabetes ever documented.

- By age 45, 50% of the Pima Indians had diabetes, which is today called type 2 diabetes.

- [Jaye] What researchers learned from the Pima helped change how we see diabetes around the world.

That rapid changes in modern life can expose risk that were already there.

- What has happened to the Pima Indians in terms of the explosion of diabetes is what the entire world is experiencing today.

Today, there are over 800 million people with diabetes worldwide.

India alone has over 200 million people with diabetes.

In the United States, we have nearly 45 million people with diabetes.

- [Narrator] Diabetes is an ancient disease, thousands of years old.

Now colliding with a modern lifestyle.

One with highly processed available food and a more sedentary life.

As a result... - In the United States, diabetes is a leading cause of healthcare costs.

- [Jaye] In 2010, Dr.

Narayan was one of the lead investigators in a brand new study launched in India called CARRS, short for the Center for Cardiometabolic Risk Reduction in South Asia.

The nationwide effort brought researchers from Emory University and leading institutions in India, such as Public Health Foundation of India, the Centre for Chronic Disease Control, all India Institute of Medical Sciences, and the Madras Diabetes Research Foundation, working together to track cardiometabolic health across urban India.

Cardiometabolic health describes how well the heart and blood vessels do their job and how the body manages energy, things like blood sugar, cholesterol, and blood pressure.

- Develop blood press and high glucose- - [Jaye] Researchers are studying households in two major Indian cities, Delhi and Chennai.

From each home, they followed one man and one woman, ordinary people representative of the population.

Every year, researchers return.

They measure blood sugar, blood pressure, cholesterol.

They ask about diet, physical activity, sleep, stress, and family history.

There were striking findings at baseline.

In the United States, about 1 in 10 adults has diabetes.

In contrast, the CARRS study found that nearly 4 in 10 adults in urban India had diabetes.

About 1/3 of men and women had high blood pressure, similar to rates in the US, but treatment rates were far lower, and 60% of participants had high cholesterol compared with 35 to 40% of US adults.

Compounding those risk, 76% of participants were sedentary.

- Why is this disease that is so readily associated with obesity happening in thin populations?

- [Jaye] CARRS researchers discovered that in many people, diabetes does not develop because of excess weight.

Dr.

Narayan says 60 to 70% of obese people never develop diabetes.

Instead, in some people, diabetes develops because the body simply does not produce enough insulin.

When insulin supply is already low, even small rises in blood sugar can overwhelm the system.

In the United States, researchers estimate about 15% of people with diabetes do not produce enough insulin.

In India, that number is as high as 50 to 80%.

CARRS has helped reveal what is happening, but understanding why the body fails to produce enough insulin remains an active and urgent area of research.

At current trends, two-thirds of people in India will develop diabetes sometime in their lives.

(horns honking) (gentle music) (jet swooshing) We begin our trip in Bengaluru in Southern India, the fourth largest city in the country with a population of almost 15 million.

It's a city of contrast, India's tech capital, buzzing with energy, innovation, and some of the most congested traffic in the country.

(horns honking) Just beyond the noise and gridlock lies a different world.

- [Suvarna] We are in the gardens of NIMHANS.

(birds singing) - [Jaye] The leafy campus of NIMHANS, the National Institute of Mental Health and Neurosciences, where quiet gardens and shaded pathways create space for reflection, and for groundbreaking science at the center of the new stage of the CARRS study, Precision-CARRS-Brain.

- Each patient is different, and each solution is also different, and each family is different, each context is different.

So it just makes for very interesting work.

In NIMHANS- - [Jaye] Dr.

Suvarna Alladi is a leading cognitive neurologist and professor of neurology at NIMHANS.

NIMHANS is India's leading institute for mental health and neuroscience, known for patient care, training, and groundbreaking brain research.

Dr.

Alladi established one of the country's first memory clinics and now leads the next generation of cognitive neurologists and researchers.

- [Instructor] What we see here are the manifestations of hypertension and diabetes in the brain.

- [Jaye] Brain donation is key to their research.

And is used to educate the public.

- [Anita] This museum is literally, I think, a temple of learning.

- [Jaye] NIMHANS Brain Museum is where visitors have an immersive experience that includes holding a real brain.

- So this is how the entire brain, spinal cord, and the nerves are engineered.

- [Jaye] Neuropathologist Dr.

Anita Mahadevan.

- [Anita] These are the nerves that are coming out of the spinal cord, and literally this is what connects you to the world.

- We are the diabetes capital of the world.

Hypertension is so common, and, unfortunately, these disorders are not treated yet.

- (indistinct) a brain health initiative.

- [Jaye] For decades, scientists have known that these conditions raise the risk of dementia.

- [Suvarna] Allan is visiting NIMHANS for the first time.

- Hi, good to see you.

- [Jaye] What looks like a simple first meeting is something much bigger.

In the lobby of NIMHANS, Dr.

Alladi welcomes Dr.

Allan Levey of Emory's Goizueta Brain Health Institute, along with Dr.

Narayan.

- Okay.

- [Jaye] 15 years into the CARRS study, this moment marks a turning point, bringing brain science directly into a project long focused on cardiometabolic disease.

- Are you doing a biorepository?

- [Jaye] NIMHANS will play a central role.

Dr.

Alladi's team will work alongside Dr.

Levey and his colleagues, analyzing thousands of brain MRIs and blood samples collected across India for signs of Alzheimer's disease.

- And recently one patient finished 12 months of the plasma exchange.

- [Jaye] For decades diabetes, heart disease, and dementia were treated as separate conditions handled by different specialists and different clinics.

- But basically it is linking the- - [Jaye] The collaboration of these researchers is recognition that these diseases are connected and that solving them requires doctors and scientists to come together across disciplines, continents, and ways of thinking.

- I'm Nitin.

- I'm Aparna Venugopal.

- I'm Pratima Ayar.

- You just cannot work in a silo.

And I mean, that is a must.

- We have people from so many different disciplines coming together.

- There is only one way of research today, and that is through collaboration.

- They just, you know, know each other well now that are working together, reviewing things together in a way that I have rarely seen.

- What Allan's group brings is a very strong rigor in Alzheimer's disease research.

(jet swooshing) - [Jaye] An hours flight east brings us to Chennai.

(gentle music) A major city on the Bay of Bengal, often called the Healthcare Capital of India.

Home to more than 10 million people, Chennai is where nearly half of the CARRS study participants live, giving researchers a window into how modern life is shaping health in Southern India.

- Every organization just rated us.

We are consistently number one.

So we kept this alone as a for-profit thing and- - [Jaye] It is here that doctors Levey and Narayan meet with India's foremost diabetes expert, Dr.

V. Mohan.

(upbeat music) - Hello, friends.

- [Jaye] Over the past four decades, Dr.

Mohan has built one of the largest diabetes networks in the world.

- Cancer patients can come, HIV patients can come.

- [Jaye] Overseeing 50 specialty clinics across India, treating over 700,000 people for diabetes.

- From all over India, from Sri Lanka, Bangladesh.

- [Jaye] With over a thousand scientific publications, Dr.

Mohan is also a lead investigator of the CARRS study, alongside members of his research team.

In his clinic, patients undergo comprehensive assessments that now include cognitive testing.

(patient speaking in foreign language) - [Announcer] Reflecting a growing understanding that diabetes affects more than just the body.

- We've always known that people from South Asia are at increased risk of developing type 2 diabetes.

- [Jaye] Dr.

Mohan also leads the Madras Diabetes Research Foundation.

- [Researcher] We will be doing it in the laboratory.

- [Jaye] Deeply involved in some of the most important diabetes and cardiometabolic research in South Asia.

As part of the CARRS cohort, scientists collect blood and other samples that are processed and stored in a world-class biobank.

These samples allow researchers to study how diabetes begins, progresses, and differs across populations, turning large scale public data into new scientific insights.

- These results can be applied globally.

80% of the world lives in low and middle income countries.

- Interesting.

- And then the third- My main role is the genomic studies, understanding, trying to see whether there are novel genes, discovery of genes, novel genes, and then trying to understand the genetics behind the whole problem.

- [Jaye] Dr.

Radha Venkatesan has been the head of molecular genetics at Madras for 26 years.

- [Researcher] They come in, they do everything.

- [Jaye] Now, her genomic studies will include the brain.

- It's absolutely an exciting time.

- So these really bothered many of the participants.

- [Jaye] At the center of the effort is Deepa Mohan who oversees field operations and data collection for the CARRS study.

Until recently, Alzheimer's screenings were not a routine part of care in India where medical attention has long centered on diabetes and high blood pressure.

With Precision-CARRS underway, that approach is shifting.

Connecting years of cardiometabolic data with new efforts to understand dementia risk.

- They're saying that- - [Jaye] An essential part of the study takes place inside participants' homes.

- The investigations include the detail, data collection on their medical history, all kinds of information that's related to the cardiometabolic diseases.

(Mr.

and Mrs.

Gopala Krishnan speaking foreign language) - [Jaye] Mr.

and Mrs.

Gopala Krishnan take turns answering questions, offering tea, sharing that their son lives in the United States in Atlanta.

- I'm not on a diet plan particularly.

- [Jaye] When researchers return for follow-up visits, blood samples will be collected.

Now, as part of CARRS-Brain, those samples will also be tested for biomarkers associated with Alzheimer's disease.

In every home we visit, there is a deep sense of gratitude for the researchers and for relationships built over time.

Participants have undergone extensive testing, completed detailed questionnaires, and given their time year after year.

- I would say we don't see them as study participants, like they are mold into like a family members.

- [Jaye] From the beginning, the CARRS study achieved exceptionally high participation, with nearly 90% of eligible adults agreeing to take part.

Remarkably, more than 15 years later, retention remains close to that level.

A testament to the trust between the researchers and the communities they serve.

(gentle music) (jet swooshing) From Chennai, we travel north to our final destination, Delhi.

(people chattering) Home to more than 25 million people and one of the largest cities in the world.

It is a city shaped by government and history, (bell ringing) vibrant street life and economic growth, but also one facing some of the most severe air pollution in the world.

This isn't fog or haze.

It's microscopic particles suspended in the air people breathe every day.

- In Atlanta, the air pollution might be 20, 30.

It's a measure of particles per million.

Here today, I think it's probably over 500 to 700.

So on a daily basis here, people are breathing, you know, well over 10 times the amount that we're breathing in Atlanta on a bad day.

And we already know with low levels, you know, there are problems with Alzheimer's disease being more common in the brain.

Even in Atlanta, that the amount of air pollution in different neighborhoods is associated with more Alzheimer's pathology in the brain.

There's gray and white matter, right?

And so you can see the different color.

- [Jaye] Allan Levey is a globally-respected cognitive neurologist and neuroscientist who leads Emory Goizueta Brain Health Institute directing cutting-edge research.

- Every day and every conversation, I see opportunities to accelerate their own research with what we've been doing back at Emory.

And they just think there's some real unique opportunities here.

- [Jaye] On this journey in India, Levey is exploring what dementia may share with these other chronic diseases long before symptoms appear.

- The things that contribute to brain disease, whether it's Alzheimer's or stroke, are very similar to those things that are driving heart disease and very likely those things driving diabetes as well.

So, you know, getting out of our little cocoons, having the ability to interact with people that have been studying in other areas, but with a different perspective.

I mean, it just makes it so much richer.

It may be that diabetes or heart disease that individually they're not the risk for Alzheimer's disease.

It's very possible that those processes that are driving diabetes are the same ones that are driving Alzheimer's disease.

- [Jaye] Thousands of participants are now undergoing cognitive testing and brain scans, expanding CARRS into one of the most comprehensive studies of brain health of its kind.

- We're doing brain imaging on 4,000 people.

This would be the largest number of brain imaging in any cohort of the world.

- [Jaye] Investigators are integrating 15 years of cardiometabolic data with new cognitive test, brain imaging, and blood-based biomarkers for Alzheimer's disease, creating a rare lifespan view of dementia risk.

(gentle music) AIIMS, the All India Institute of Medical Sciences, is India's flagship medical institution, a major center for patient care, medical training, and research.

There is never a slow day here.

(people chattering) Nikhil Tandon is the Head of Endocrinology at AIIMS.

- Since our annual outpatient footfall is one Denmark a year, it's just under five million patients in a year.

- [Jaye] You see five million?

- Five million patients.

- [Jaye] In one year?

- In one year.

- [Jaye] Mixed in with people who travel from across the country to be treated here are CARRS participants.

Participants receive retinal imaging scans.

- [Aripa] Right now, I'm using the Topcon- - [Jaye] Optometrist Aripa Shy.

- [Aripa] And I'm also checking the pressure of the eye.

- [Jaye] They undergo cardiac scans, vision tests.

(patient speaks indistinctly) (EKG warping) - [Jaye] EKGs and paper and pencil cognitive testing.

(test speaking in foreign language) - [Jaye] Ishwar Singh Goyal is a longtime study participant and former member of Parliament with a history of hypertension and diabetes.

- They will help our peoples for the health, for the heart, for the kidney, for the liver.

- [Jaye] And for the brain.

And for the brain.

What sets CARRS apart is not just what researchers measure, but where they measure it.

Year after year, they return to participants' homes.

- Survey people came from CCDC in 2014.

- [Jaye] 73-year-old Ramesh Ramnani lives with his 71-year-old wife, Hardavi.

- In the comfort of my home, they conducted all kind of tests.

- [Jaye] As researchers visit their home, Hardavi prepares fragrant tea for everyone.

You work so hard.

- Thank you very much.

- [Speaking] So she's boiling.

- A ritual reflecting the warmth and care at the center of their home.

What are your favorite plants?

As for Ramesh, he has mobility issues, but is otherwise in good health.

- Overall health is good, very good.

- [Jaye] In another Delhi neighborhood, 65-year-old Gurdeep Kaur is also part of this study.

She lives with diabetes and thyroid issues, and when she joined the research in 2014, she welcomed the thorough testing as a way to better understand her health.

- So she was very happy to know that all the tests will be performed in her home.

- [Jaye] By visiting participants in their homes year after year, researchers don't just collect data, they see how people live.

They observe family structures, daily routines, support systems, and the environments people age in, offering insight into how social and lived experiences may shape long-term health and wellbeing.

- I'm the Executive Director of Centre for Chronic Disease Control.

- [Jaye] Cardiologist Dorairaj Prabhakaran heads the CCDC, the coordinating hub for the CARRS study.

Prabhakaran is an epidemiologist and public health researcher.

- 80% of the deaths, cardiovascular disease deaths in US, UK, or Europe is after the age of 70 years.

By contrast in India, nearly 52% of deaths occur before the age of 70 years.

- [Jaye] Prabhakaran says only 20% of people in urban India and just 10% in rural India had their blood pressure under control, putting millions at higher risk for heart disease and heart attacks.

(machine beeping) CCDC plays a central role in CARRS coordinating study operations, processing data, and supporting laboratory work for samples collected in the field.

Biochemist Ruby Gupta is the head of the lab at CCDC.

- The phlebotomists go to the field, to the community, and collect the samples.

Samples means we collect blood and urine from the participants, and they bring it to here in the lab.

- [Jaye] Each year, more than 6,000 samples are processed through these labs.

With the Brain portion of the CARRS study now underway, selected samples are forwarded to Dr.

Alladi and her team at NIMHANS.

- [Ruby] We are collecting the samples.

We'll be sending the samples to NIMHANS and the analysis will happen there.

The biomarker related to brain will happen there.

(bright music) - [Jaye] From community clinics and diabetes foundations to major institutions like AIIMS and the Centre for Chronic Disease Control, this is a broad, coordinated effort to understand what drives chronic disease and how it may impact the brain long before symptoms appear.

It's a shift from treating disease late to understanding how it begins.

- We should stop thinking of dementia and diabetes and other diseases as separate because ultimately they are connected.

- [Jaye] Research increasingly shows many risk factors that drive not just dementia, but diabetes, high blood pressure, and high cholesterol are modifiable.

The hope?

That people have the ability to improve their health and reduce their risk through physical activity, healthy food, managing blood pressure, cholesterol, and blood sugar, reducing pollution exposure, staying socially and mentally engaged.

The lessons emerging from this study won't remain in India.

They apply to populations everywhere, including here in the United States.

By following people over time, this research offers something powerful, the chance to intervene earlier, to slow disease before it takes hold, and to rethink how we protect the brain across the lifespan.

- Scientists are like adventurers.

They go out to discover.

This collaboration between the United States and India is becoming richer by the day.

(gentle music) - Lack of sleep is supposed to be a risk factor.

- [Jaye] All the key players in the CARRS study in one room in Delhi for a few days, comparing findings and mapping what comes next in this 15-year journey.

It is a lifetime commitment to science, work that will save lives.

And here in India, (people singing) where music, dance, and community are woven into daily life, progress is something shared.

Celebration is not separate from work.

It is part of a culture that values connection, collaboration, and the power of the collective effort.

By understanding how disease begins, we may finally learn how to prevent chronic disease and dementia, not just for one country, but for the world.

(people singing) Standing at the Taj Mahal, a monument to what human beings can achieve, we're reminded by the CARRS study that new discoveries can change lives around the world.

And that's gonna do it for us this week.

I'm Jaye Watson in India.

See you next time on "Your Fantastic Mind."

(intriguing music) (intriguing music continues) - [Announcer] "Your Fantastic Mind" brought to you in part by Sarah and Jim Kennedy.