Top 5 medical advances of 2024

As 2024 comes to a close, we look back on five exciting medical advances coming from the Feinstein Institutes for Medical Research — the research arm of Northwell Health. In this episode, we spotlight studies that made strides in the treatment of Alzheimer's disease, lung disease, mental health and dysphagia. 

Read more about these five notable Northwell advances of 2024.

Chapters:  

• 01:05 — The dark side of genetics and psychiatric disorders | Douglas F. Nixon, MD, PhD
• 05:21 — Sex, gender identity linked to human brain activity | Elvisha Dhamala, PhD
• 10:22 — Rethinking thick liquid diets | Liron Sinvani, MD
• 15:39 — Recognizing psychosis in Alzheimer's patients | Jeremy L. Koppel, MD
• 20:33 — Researchers focus on the spleen to treat the lungs | Stavros Zanos, MD PhD

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It'sbecome a tradition each December for us to look back at some of the top
researchadvances coming out of the Feinstein Institutes for Medical Research,
the research arm of Northwell Health.
And the past 12 monthshave given us much to talk about.

(00:30):
Researchersat the Feinstein Institutes have made meaningful strides
in understanding risk for diseaseslike pulmonary hypertension,
Alzheimer'sdisease, and schizophrenia.
We'relearning more about how biological factors shape sex and gender.

(00:50):
And we'regathering information about care for patients with trouble swallowing,
that could informhow best to manage their care.
Up until recently,
98 to 99% of the humangenome was considered junk DNA,

(01:14):
meaning it doesn't influencethings like our appearance, health,
or other aspects of our biology.
But new research from Dr.
Douglas Nixon, Director of Feinstein'sInstitute for Translational Research,
is challenging that notion.

Dr. Nixon (01:35):
When the human genome was originally sequenced,
it was a big shock to everyonebecause only about 1 to 2% of
thehuman genome was coding for genes.
That was a surprise.
And themajority of the genome is other stuff.
And I becamevery interested in that other stuff.

Sandra Lindsay (01:58):
Along with experts from King's College, London, Dr.
Nixon made headlines in 2024 witha study proving this other stuff isn't
junk at all and in fact, couldbe influencing our mental health.
Dr. Nixon and his team chose to studyhuman endogenous retroviruses,

(02:22):
which have been embeddedin our DNA for millions of years.
Passed from parents to children,they were thought to be dormant.

Dr. Nixon (02:32):
As a virologist,
I wasshocked to find that 9% of everyone's genome is actually the remnants
of ancient infectiousviruses that are sitting in our genome.
And very few people have actuallybeen studying what these might do.

Sandra Lindsay (02:53):
And no one had ever looked at the connection between
theseremnants and psychiatric disorders.

Dr. Nixon: No one, until we came along, had put two important components together. (03:01):
undefined

Sandra Lindsay: The researchers reviewed existing records about genes and disease risk. (03:06):
undefined

Dr. Nixon: Many of us who've done 23 or me or ancestry will understand that (03:12):
undefined
if you have a certain gene,then you might have a higher risk.

Sandra Lindsay (03:21):
They compared two large, seemingly unrelated data sets.
One, which Dr. Nixon helps create,
cataloged the locationsand types of human endogenous retroviruses in human DNA.
Theother looks for correlations between specific genetic variations and,

(03:44):
and the likelihoodof developing a particular disease,
as well as how active a gene isand how that relates to disease risk.

Dr. Nixon (03:54):
When we put these human endogenous retroviruses into this genetic risk method,
whatsurprised us and what we wrote the paper about Is we found that a large
component ofthe risk for developing schizophrenia or major depressive disorder
could actually berelated to variation in the inherited

(04:17):
endogenous retrovirusesthat we get from our parents.
For the first time, we're nowbeing able to think about the biology,
the genetics of psychiatry
buried in the dark genome.

Sandra Lindsay: And dark genome is yet another name for that other stuff or junk DNA. (04:30):
undefined
Now Dr.
Nixon said they are exploringwhether any of these endogenous
retrovirusesthey identified can produce proteins.

Dr. Nixon: Because if they can produce proteins, (04:50):
undefined
thenthere may be an easier biomarker which we could look in blood
to see and monitor peopleliving with schizophrenia who are
currently undertreatment. The work that we've done,
I'm hoping will lead tonew treatment options in the future.

Sandra Lindsay (05:22):
2024 brought much conversation on sex and gender in
the publicsphere as well as among researchers.

Dr. Dhamala: A lot of people are just getting excited about a lot of these different (05:31):
undefined
opportunities foravenues of research that we can go
down that justhaven't been explored in the past.

Sandra Lindsay: That's Dr. Elvisha Damela, (05:40):
undefined
Assistant professor in the Instituteof Behavioral Sciences at the
Feinstein Institute, interestedin advancing these conversations.
Dr. Damela recentlyauthored a paper on the neurological
drivers ofsex and gender in early development.

Dr. Dhamala (06:03):
I'm really passionate about just understanding how sex and gender influence
our day to day lives.
Theyinfluence our health, our behavior.

Sandra Lindsay: The research was based on precise definitions of sex and gender. (06:11):
undefined

Dr. Dhamala: In this study, specifically, (06:16):
undefined
we defined sex assex assigned at birth and we only had
informationabout binary sex, so male and female.
In terms of gender,
we actually considered it alonga continuum and we considered
both how the children andthe parents reported their gender,
and we considered it interms of gender identity, belt gender,

(06:37):
gender contentedness, genderexpression, as well as sex type,
behaviorduring play, and gender dysphoria.

Sandra Lindsay (06:44):
An important distinction in her research because
of theways the two might inform treatment.

Dr. Dhamala: Especially in the last decade, (06:51):
undefined
therehas been a lot of emphasis to try and understand how sex differences in
brain andbehavior might actually make men or women more vulnerable to specific
illnessesand see how we might actually be able to develop sex therapeutic
interventions that aremore effective than just general ones.
So now if wealso add in this component of gender,

(07:12):
it can furtherlead us to the pathway towards precision medicine where we can
actually take in information aboutdifferent people's identities and use
that to actually come up with a planthat's most appropriate for them.

Sandra Lindsay (07:24):
The paper analyzed data on sex and gender collected
in a large scale study of children.

Dr. Dhamala: So this is Data from the Adolescent Brain Cognitive Development, (07:32):
undefined
orthe ABCD study, which is an ongoing longitudinal study of development,
and it includesclose to 12,000 youth in total.
And thesekids are being followed throughout the course of development.
Theywere recruited at about ages 9 to 10,
and they're beingfollowed longitudinally for 10 years.

Sandra Lindsay (07:51):
She was able to process this data with the use of a machine learning algorithm,
or AI that teaches itself to scandata sets and recognize patterns.

Dr. Dhamala: So we looked at relationships between the brain data and sex, (08:04):
undefined
and then we also separatelylooked at the relationships
between the brain data and gender.

Sandra Lindsay: One of the main takeaways for Dr. (08:12):
undefined
Damela relatedto the ways sex and gender are
bothshaped by connections in the brain.

Dr. Dhamala: So this study actually shows that sex and gender both map onto the brain, (08:22):
undefined
and the waysin which they map onto the brain
areactually different from one another.
What we see is that sex influencesbrain regions that are involved
in visual processing,sensory processing, motor control,
as well as regionsinvolved in executive function.
Whereas gender wasmore dispersed and it had a broader

(08:44):
influence throughout the entire brain.
And these included large areas thatare involved in executive function,
including things like attention, socialcognition, and emotional processing.

Sandra Lindsay: And although discourse around sex and gender usually arises in relation (08:54):
undefined
to the LGBTQIA+community, Dr. Dhamala explained

Dr. Dhamala: Every single person. Has a gender, and that influences who we are. (09:05):
undefined
And we see thatit clearly also influences our brain.
So it's not actually just individualsthat might identify as non binary,
gender fluid or genderqueerthat this is going to affect.
Thisactually affects every single person.

Sandra Lindsay (09:21):
The study supports the idea that sex and gender don't necessarily stop forming.
Rather,
the potentialfor these neurological frameworks
toevolve and reshape remains for life.

Dr. Dhamala: I think it's important to recognize that a lot of these aspects of who we are (09:35):
undefined
and our biologydoes change significantly throughout the course of development.
So as these kids go through puberty,
go throughlife changing experiences throughout the course of adolescence their
brains are still developingand they are also still continuing

(09:58):
to develop in terms ofwho they are and how they identify.
So it'll be really important to actuallylook at whether these relationships
thatwe found stay consistent throughout the course of development,
or ifit's actually going to change in some way that might be more relevant,
especiallywhen we start to think about how this
couldaffect adults or people in older ages.

Sandra Lindsay (10:25):
Next,
wetake a look at a study that assesses dietary care for hospital patients.

Dr. Sinvani (10:32):
It's interesting the way this, this all started.
It kindof almost happened by, by chance.

Sandra Lindsay (10:37):
Dr. Liron Sinvani,
assistant professor at the FeinsteinInstitute of Health System Science
and director of Northwell'sGeriatric Hospitalist Services,
is hoping to ease the burdenfor older hospital patients who
have trouble swallowing,a condition called dysphagia.

Dr. Sinvani (10:59):
So about a third of older adults will suffer from dysphagia,
which isthis trouble or difficulty swallowing.
In the hospital,
it's even more prevalent thanin hospitalized people with dementia.
It's itaffects up to almost 90% of patients.

Sandra Lindsay (11:16):
The standard for feeding patients with dysphagia has been thick liquid diets.

Dr. Sinvani (11:22):
When we swallow liquid, thin liquids, it comes in fast, right?
Because it's thin liquid, you drink it.
And for a person who has dysphagia,
it can be difficult to kind of handlethat and control it as it's going down.
Whereas if you thickenthe fluid, they have more control of it.
It moves slower so theycan swallow it with more confidence.

Sandra Lindsay: This diet also involves cutting up, (11:43):
undefined
mincing or pureeing foods to makethem soft and easier to swallow.
If foreign objectslike food are inhaled into the lungs,
it canlead to a dangerous lung infection called aspiration pneumonia.

Dr. Sinvani (12:01):
It can cause choking, which is very, very scary.
It can cause people to just cough andlike struggle to breathe for a second.
And we knowthat that leads to poor outcomes.
You know, pneumoniais very dangerous in older people.

Sandra Lindsay (12:17):
Although thick liquid diets were put in place with safety and comfort in mind,
they can often be counterproductive.

Dr. Sinvani (12:25):
Imagine let's say that you,
it's a hot day and you're verythirsty and you want to drink water.
And I say, well, you can havewater, you have to drink honey, right?
Andit's not the most like hydrating thing.
And people tend to, to be thirst.
It's really hard to explain, especiallyto someone with dementia, let's say,

(12:46):
or cognitiveimpairment, Alzheimer's disease,
where they just reallywant the food that they're used to.
And of course, the most frustratingpart is if that person is crying,
I'm thirsty,I'm thirsty, or I don't like this food,
allof a sudden now they're not eating.
Then it's a major quality of life issue.

Sandra Lindsay (13:02):
A few years back, Dr.
Sinvani was askedto contribute to a medical journal.
This problemwith thick liquid diets came to mind.

Dr. Sinvani (13:12):
I had a patient who was admitted with aspiration pneumonia and with dysphasia.
And I wasthinking like, what's the evidence?
Why amI putting this person on a dysphasia diet when they hate it so much?
And I was looking at the literature.
AndI saw, really, there wasn't much to.
Supportthis universal practice that we all do.

Sandra Lindsay (13:31):
With funding from the National Institute of Aging, Dr.
Sinvani andfellow Feinstein Institute's researcher
Dr. Alex Makhnevich,
enlisted a teamof data analysts to comb over 40,000
patient recordsdrawn from 11 Northwell hospitals.

(13:54):
Their goalwas to figure out whether thick liquid
dietsinfluence mortality in these patients.
What they discovered was stunning.

Dr. Sinvani: There was no difference in mortality, (14:05):
undefined
which is significant.
And then, you know,
it did show that the thick liquidshad increased risk of respiratory
complicationsbut decreased risk of intubation.

Sandra Lindsay: This outcome raises important questions about the benefits (14:20):
undefined
of thick liquid dietsfor dysphagia management, and Dr.
Sinvani says, requires more researchto improve guidelines on its use.

Dr. Sinvani: Because this is a retrospective study, (14:35):
undefined
we're notsaying that we should be changing management based on our study.
There are probably patients thatwould benefit from thickened liquids
and dysphagia diets, but thereare probably patients that don't,
where the impact on qualityof life sort of overtakes the benefit.

(14:59):
The bottomline from our study is to show that
thingsmay not be as clear cut as we think.

Sandra Lindsay (15:05):
Dr. Sinvani also hopes that her research inspires caregivers
to thinkcritically about the care they provide.

Dr. Sinvani (15:14):
Just because something is a standard of care doesn't mean that
it's necessarilybacked by rigorous evidence.
Right?
And I thinkthat's, that's an important lesson.
It's okay to question thingsand to question common practices.

Sandra Lindsay: Alzheimer's disease is devastating, (15:46):
undefined
robbing individuals of their memoriesand often their sense of self.
But for many, the disease bringsanother heartbreaking symptom.

Dr. Koppel: Psychosis is probably the most severe syndrome, behavioral syndrome, (16:00):
undefined
thatpeople with Alzheimer's experience.

Sandra Lindsay: That's Dr. Jeremy Koppel, (16:08):
undefined
co directorof the Litwin Zucker Research center at the Feinstein institutes and
co author of a study that couldhelp detect this often overlooked
aspect of Alzheimer'searlier, using a simple blood test.

Dr. Koppel (16:27):
Psychosis is something that affects 40 to 50% of people,
probablyover the course of their disease.
Women morethan men, very difficult to manage.

Sandra Lindsay (16:37):
And very often families don't make the connection.

Dr. Koppel (16:41):
So they'll come and they'll say, listen, yes, he has Alzheimer's,
but he has another problem.
And they'll describe it, andthey are not aware that it's related.
And so it doesn't really getthe appropriate treatment early on.

Sandra Lindsay (16:54):
But new research is offering a glimmer of hope.
Dr.Koppel and his team are investigating whether a simple blood test
could predict the onsetof psychosis in Alzheimer's patients.
The Key lies in proteinslike amyloid and tau, spelled tau,

(17:15):
which helpmaintain the structure of brain cells.
In Alzheimer's, taubecomes abnormal and accumulates,
contributingto the death of these cells.

Dr. Koppel (17:27):
Amyloid builds up outside of brain cells.
Tau builds up inside of brain cells.

Sandra Lindsay: Increased levels of these two proteins are the hallmark sign (17:33):
undefined
of Alzheimer's disease.But detecting them is no easy task.

Dr. Koppel: We did spinal taps for years. (17:43):
undefined
We stilldo because that was the only way we could see some of these proteins.

Sandra Lindsay: While these proteins are shed from the brain into the bloodstream (17:49):
undefined
where they can be measured, theycirculate at very low concentrations.

Dr. Koppel (18:00):
Which would make it really hard to detect them.

Sandra Lindsay (18:01):
But advances in technology over the last decade have solved for this issue in
theform of highly sensitive blood tests that uses antibodies or immune cells
to seek out and latch onto specifictarget proteins, in this case tau.

Dr. Koppel (18:21):
So what we did is we took these very critical proteins
thatare used to diagnose Alzheimer's,
and we lookedat the concentration of those in
the bloodof people who had become psychotic.

Sandra Lindsay: Dr. Kopel and co author on the paper, (18:32):
undefined
Dr. Jesus Gomar,
analyzed blood samples from nearly1,000 participants in the Alzheimer's
Disease NeuroimagingInitiative, a large ongoing study.
These individualshad provided blood samples and undergone cognitive testing

(18:54):
over several years. Somedeveloped psychosis, others did not.

Dr. Koppel (19:00):
So it turns out, before they became delusional or developed hallucinations,
the tau in their blood began to go up.
And when welooked at people who never became psychotic but had Alzheimer's,
their tau sort of remained flat.
The concentrationdidn't change. It was much higher than if they were healthy,
but it didn'tchange. If they never got psychotic,
if theywere getting psychotic, it went up.

Sandra Lindsay: Then, they discovered something even more revealing. (19:23):
undefined

Dr. Koppel (19:28):
When they actually had a episode of psychosis, it fell.
After that, it never reachedthe level of a healthy control.
Butit looked like there was this rise and fall that always remained elevated,
but looked really, really differentthan non psychotic Alzheimer's.
That's important because that tellsyou that there's something dynamic
about Tao in psychosis that'snot true once you get Alzheimer's.

Sandra Lindsay (19:54):
This finding was further supported by examining brain
tissue postmortem from a separate data set,
confirming the link betweentau and the very earliest stages
of psychotic Alzheimer's,even before symptoms appear.
This discoveryhas the potential to revolutionize

(20:17):
how we approachAlzheimer 's-related psychosis.
Early detection through a bloodtest could lead to earlier intervention
and the developmentof safer, more effective treatments.
Last but notleast, we spoke to Dr. Stavros Zanos,

(20:39):
researcher andassociate professor at the Feinstein
Institutesand the Zucker School of Medicine.
He and his team are exploringa new non invasive treatment
option for an often fatal lung disease.

Dr. Zanos (20:55):
Pulmonary hypertension means high blood pressure inside the vessels of the lung.
One typecalled pulmonary hypertension (PAH)
It's the most complextype of pulmonary hypertension.
In manyof these patients with the disease,
the PAHhave what we call vasoconstriction of the pulmonary arteries,

(21:18):
so thearteries are constantly constricting.

Sandra Lindsay: Current FDA approved treatments focus on relaxing the lungs blood (21:21):
undefined
vessels to lowerpressure. They improve quality of life,
but don't address the underlyingcause or improve long term survival.

Dr. Zanos: And most of them actually die within less than 10 years after diagnosis. (21:37):
undefined
So it's a very severe and fatal disease.

Sandra Lindsay: With patients and their doctors desperate for better options, (21:44):
undefined
Dr. Zanos is nowtesting a treatment that he thinks
couldaddress the underlying cause of PAH.

Dr. Zanos: Immune system dysfunction and inflammation play a role in how this (21:57):
undefined
disease gets worse andworse, or even perhaps how it starts.

Sandra Lindsay (22:07):
When inflammation becomes excessive, it starts to do more harm than good.
Ratherthan healing an injury, it can damage critical structures in the body,
including organs. One way to treatthis is by stimulating the vagus nerve,
which controls the level orintensity of inflammation in the body,

(22:30):
among other responsibilities.
One type of vagus nerve stimulationuses ultrasound technology.
While best known as an imaging toolused to monitor fetuses in the womb,
it canand has been used as a treatment.

Dr. Zanos (22:49):
Focused ultrasound neuromodulation is using the same technology
or a similar technology thistime to generate mechanical waves,
just like with imaging,
but of certain parameterswith certain characteristics
thatactually change the way cells work.

Sandra Lindsay (23:07):
In their study, they targeted a nerve in the spleen called the splenic nerve.
Dr.Zanos said they chose this based on prior research showing that it helps
suppressthe immune response throughout the
bodywhen activated through stimulation.
But what does a nerve inthe spleen have to do with the lungs?

Dr. Zanos: It doesn't have a simple answer. (23:30):
undefined
The short answer is wedon't know, but we have some ideas.
The core of the hypothesis,
we change somethingin the nerve of the spleen that results
in an immune changein these cells inside the spleen,
resulting in a suppressionof inflammation throughout the body,

(23:51):
especially in that part ofthe body that is dysfunctional in PAH,
which is the lungs.

Sandra Lindsay (23:56):
To test it, Dr.
Zanos andhis team applied focused ultrasound treatments to rats with pulmonary
arterialhypertension, or PAH, 10 minutes a day, every day for two weeks.
After the two weeks,
the researchers comparedthe treated rats to a control group

(24:17):
that hadn't received treatment.

Dr. Zanos: So the animals that had received treatment at the end of two weeks, (24:19):
undefined
we found that they had reducedone of the major markers of severity
of the disease, whichis the pressure inside their lungs.
Itwas about 30% less than the pressure in animals that were treated with the
SAM treatment. So that was thefirst finding that kind of alerted us,

(24:42):
and we thought,okay, there's something here, right?
But doesthis translate to people with pah?
Wehave no idea. Lots of open questions.
So there are questions on the,let's say, mechanistic side of things.
There are questions related to thetechnology development, and finally,
there are clinical questions.

Sandra Lindsay (25:01):
Dr. Zanos said they are actively looking into all of these questions and
hope to test thisvagus nerve stimulation treatment in people with PAH in the coming years.

Dr. Zanos (25:10):
By maybe modifying the natural progression of the disease,
maybe we can increasethe life expectancy for these people
which would be greatbecause right now it's pretty bad.

Sandra Lindsay: A sincere thank you to Drs. (25:29):
undefined
StavrosZanos, Jeremy Koppel, Liron Sinvani, Elvisha Dhamala, and Douglas Nixon.
What an incredible lineuprepresenting the brilliant minds
at the FeinsteinInstitutes for Medical Research.

(25:49):
They've given usa glimpse into the future of medicine,
and2025 is looking brighter than ever.
While our countdown traditionallymarks the end of our podcasting year,
wehave a heartwarming treat in store.
Tune in later this weekfor a very special episode featuring

(26:10):
the wisdomand delightful innocence of children.
They'll be sharing theirNew Year's resolutions for grownups,
offering a freshperspective on what truly matters.
As we head into 2025,
it'sthe perfect way to wrap up a year of exploring health and and well being.

(26:30):
On behalf of theentire 20 minute health talk team,
thank youfor being a part of our community.
We wish youa joyful and healthy holiday season.
I'm Sandra Lindsay, andthis has been 20-Minute Health Talk.