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Alzheimer’s disease

These composite brain images from the study of WTC responders reveal evidence of amyloidosis. Areas shaded in red and yellow indicate regions of the brain with amyloid. Image courtesy of Sean Clouston, Stony Brook Medicine

By Daniel Dunaief

Even over 23 years after first responders raced to the smoldering site of the World Trade Center terrorist attacks, many emergency crews continue to battle the effects of their exposure.

With a combination of toxic aerosolized particles infusing the air, first responders who didn’t wear personal protective equipment and who had the highest degree of exposure have suffered from a range of symptoms and conditions.

Sean Clouston

In a recent study of 35 World Trade Center first responders in the Journal of Alzheimer’s Disease, lead author Sean Clouston, who is a Professor in the Department of Family, Population and Preventive Medicine in the Renaissance School of Medicine, found evidence of amyloid plaques, which are often linked to Alzheimer’s Disease.

The paper links exposure to a neurodegenerative protein.

Research with World Trade Center first responders not only benefits those who worked tirelessly to try to find survivors and to restore the area after the attack, but also could help other people who inhale aerosolized toxins.

Indeed, such research could help those who are spending hours battling the ongoing wildfires in Los Angeles, which have been consuming forests and trees, homes and commercial buildings, at a furious and uncontrolled pace.

People have a feeling that fresh air is safe, but what scientists have learned from their studies of the World Trade Center first responders is that “just being six feet away from a pile of rubble that’s smoldering, even if you can’t see that it’s dangerous, doesn’t mean it isn’t,” said Clouston. “There is at least some risk” to human health from fires that spew smoke from burned computers and refrigerators, among others.

Given the variety of materials burned in the fires, Minos Kritikos, Senior Research Scientist and a member of the group in the collaborative labs of Clouston and Professor Benjamin Luft, suspects that a heterogeneity of particles were in the air.

People in Los Angeles who are inhaling these particles can have them “linger in their circulation for years,” said Kritikos. “It’s not just a neurological issue” as the body tries to deal with carrying around this “noxious” particulate matter. Since most neurons don’t regenerate, any toxicity induced neuronal death is irreversible, making damage to the brain permanent.

Even in non-emergency situations, people in polluted cities face increased health risks.

“There is a recognition that air pollution is a major preventable cause of Alzheimer’s Disease and related dementias, as noted by the latest Lancet Commission,” Clouston explained.

Two likely entry points

People who breathe in air containing toxic chemicals have two likely pathways through which the particulates enter the body. They can come in through the nose and, potentially, travel directly into the brain, or they can enter the lungs, circulate through the body and enter the head through the blood-brain barrier. The olfactory route is more direct, said Kritikos. 

Minos Kritikos in front of Stony Brook Hospital.

The amyloid plaques in these first responders was found primarily in the area near the nose, which supports the idea that maybe inhaling the dust was the problem, Clouston said.

Once these chemicals enter the brain, Clouston and his team believe the body engages defenses that are designed much more for viruses than for toxic compounds. The immune system can encapsulate these chemicals in amyloid plaques.

Amyloid plaques, in moderation and under conditions that protect the brain against pathogens, are a part of a protective and helpful immune response. Too much of a good thing, however, can overwhelm the brain.

“When there’s too much plaque, it can physically disturb neuronal functions and connections,” said Kritikos. “By being a big presence, they can also molecularly and chemically react with its environment.”

A large presence of amyloid can be toxically necrotic to surrounding neural tissue, Kritikos added.

What the scientists believe they are tracking is the footprint of an adaptive response that may not help the brain, Clouston added.

Clouston cautioned that the plaques and cognitive decline could both be caused by something else that scientists haven’t yet seen.

The findings

The research, which used positron emission tomography and magnetic resonance imaging scans to search for evidence of amyloid plaques, found evidence that doesn’t look like old age Alzheimer’s, explained Clouston. Usually these levels of plaques are not located in one spot, but occur throughout the brain during Alzheimer’s. 

The immune response may be causing some of these plaques.

The amount of amyloid plaque doesn’t look like Alzheimer’s Disease and does not appear abnormal in the traditional way of testing, but with careful analysis of the olfactory system, the researchers can find elevated levels.

“I was surprised by how little amyloid was necessary to show this association,” said Clouston.

Researchers at Mt. Sinai have examined the effect of exposure to these same particulates in mice.

“The answer is very much similar to what we see in humans,” said Clouston. “That supports this work.”

To be sure, Clouston and Kritikos are hoping to build on this research. They are particularly interested in following up with participants to measure the rate of change in these plaques from the observed amyloid signals they measured at baseline.

“Doing so would enable us to calculate the rate of amyloid buildup allowing us to assess our responders more precisely, opening doors to possible therapeutic interventions such as the recently approved anti-amyloid therapies,” Kritikos explained. 

Additionally, they hope to expand on the study beyond the 35 people who participated.

It is unclear whether tamping down the immune system could make patients better or worse. By reducing amyloid plaques, scientists might enable the harmful dust to cause damage in other areas of the brain. Alternatively, however, a lower level immune response with fewer plaques might, in the longer term, be better for the brain.

This study “does open the door for some of those questions,” Clouston said. Kritikos and Clouston plan to study the presence of tau proteins and any signs of neurodegeneration in the brains of these first responders.

“More research needs to be done,” Clouston said, which specifically targets different ways of measuring exposure, such as through a biomarker. He’s hoping such a biomarker might be found that tracks levels of exposure.

Future research could also address whether post traumatic stress disorder affects the immune response.

“It’s certainly possible that PTSD is playing a role, but we’re not sure what that might be,” said Clouston.

The researchers are continuing this research as they study the effects of exposure on tau proteins and neurodegeneration.

“We are hopeful that this will be an important turning point for us,” Clouston explained

From the Medditerranean to the Atlantic

Born and raised in Cyprus, Kritikos comes from a large family who are passionate about spending time with each other while eating good food.

He earned his doctorate from the University of Bristol in England.

Kritikos met his wife Jennifer LoPresti Kritikos, who is originally from Shirley, New York, at a coffee shop in Aberdeen, Scotland, where he was doing postdoctoral research.

LoPresti, who works at Stony Brook as the Department Head Administrator for Biomedical Engineering, and Kritikos live in Manorville and have an eight year-old daughter Gia and one-year old son Theseus.

As for his work, Kritikos is grateful for the opportunity to contribute to research with Clouston and Luft, who is the Director of the Stony Brook WTC Health and Wellness Program.

“I’m happy to be in a position whereby our large WTC team (the size of a small village) is constantly pushing forward with our understanding for how these exposures have affected” the brain health of WTC first responders, Kritikos explained. He would like to continue to uncover mechanisms that underly these phenomena, not just for WTC responders but also for similarly exposed populations.

 

Stephen Post

By Daniel Dunaief

Thieves come in all shapes and sizes, robbing people of valuable possessions or irreplaceable personal keepsakes.

Diseases such as Alzheimer’s disease and forms of dementia also rob people, taking away their memories, connections to their past and even their sense of themselves.

At times, however, people who are battling these conditions can emerge from its clutches, offering a fleeting, or even longer, connection to the person their loved ones knew, the passions they shared, and the memories that helped define a life.

In a study published in November in the Journal of Alzheimer’s Disease, Stephen Post, Director of the Center for Medical Humanities, Compassionate Care and Bioethics at Stony Brook University, gathered information from surveys with 2,000 caregivers who shared their reactions to unexpected lucidity from forgetful people.

“Caregivers can find inspiration in these fleeting moments,” Post wrote in a summary of the conclusions of the study. “The research aims to guide caregivers and enhance the understanding of the enduring self-identify of deeply forgetful people, promoting compassionate care and recognizing the significance of our shared humanity.”

Such moments of clarity and awareness, at levels that can be more engaging than the typical behaviors for people suffering with various levels of forgetfulness, can be rewarding at any point, but can offer a particular gift to caregivers and families around the holidays.

Possible triggers

Post suggested that these moments of lucidity can be purely spontaneous and surprising. They  can also arise during an intervention, when a caregiver or family member provides some specific stimulation or memory trigger.

“Caregivers can sing a song that their loved ones identify with from earlier in life,” said Post. “We’ve done that here at the Long Island State Veterans Home on the Stony Brook campus.”

Several years ago, Post wrote about a room of 50 veterans, many of whom spent a good part of their days in a haze without acting or interacting with others.

When they heard “The Star Spangled Banner” or other patriotic music, as many as 70 percent reacted and started to sing the song. The duration of participation varied, with some saying a few words or a line, others singing a verse, and still others making it through the entire song, 

After the song, people who might have seemed out of reach could react to closed-ended questions. This could include choices such as whether they preferred toast or cereal for breakfast.

“A good half of them were able to respond and sometimes even carry on a brief conversation,” Post said.

Art can also help draw out forgetful relatives. Groups around the country are taking forgetful people and their caregivers to art museums in small groups. Looking at a famous or particularly evocative piece of artwork, people might express appreciation for the magnificence of a painting.

Poetry can also serve as a stimulus. Forgetful people who listen to the poems of Robert Frost or other familiar writers can respond with the next line to words deeply ingrained in their memory.

“Their affect picked up,” said Post. “They were smiling, they were excited and enthusiastic. That’s great stuff.”

These moments can provide a connection and offer joy to caregivers.

Other possible triggers include smells, such as the familiar scent of a kitchen; interactions in nature, such as the feel of snow on someone’s face; or playing with pets.

The forgetful can “respond joyfully to dogs,” said Post. “It can remind them of [a particular] dog from 30 years ago.”

Additional research

Caregivers who help forgetful people through their daily lives sometimes struggle with the question of whether “grandma is still there,” Post said. That metaphor, however, can miss the “hints” of continuing self identity.

The National Institute on Aging has funded Post’s study on what’s happening with the brain during these moments of lucidity. 

A challenge in that research, however, resides in doing PET scans or collecting other data when those moments are spontaneous and unpredictable.

The work from Post’s recent study indicates that these periods of clarity are important for the morale of caregivers, with many of them feeling uplifted from the interaction.

Post sees further opportunity for study. In his next project, he hopes to cover how to operationalize this information into an intervention. “It’s very practical, very real and can do a heck of a lot” for the forgetful and their caregivers, he said.

To be sure, some forgetful people may not respond to some or all of these cues, as the damage from their diseases may have made such outreach and actions inaccessible.

When these moments, fleeting though they may be, occur, they can be rewarding for caregivers, family members and the forgetful themselves.

Jean Mueller with her late mother Geraldine and her father Daniel.
Photo courtesy of Jean Mueller

Jean Mueller, Assistant Director of Nursing/ Project Manager in the Department of Regulatory Affairs, Patient Safety & Ethics at Stony Brook, recently spent time with her father Daniel, 95. The elder Mueller lost his wife of 74 years Geraldine several weeks ago and is in an assisted living facility.

Taking her father out was too difficult, as it could cause agitation and confusion.

“We went and had Thanksgiving dinner with him there,” Mueller said. “He seemed to really enjoy it, in the moment. He knew the food and he knew it was a holiday. He didn’t ask me where my mom was.”

The interactions can be challenging, as she sometimes feels like she’s pulling “all the strings and you don’t know what you’re going to get” when she interacts with him, she said.

Still, Mueller suggested that it doesn’t matter whether he remembers her visits.

“In the moment, he matters, it matters and he’s still a person,” she said. ‘When you get to the point where everything has been taken away from you, and you lost your independence, even if it’s for a short period of time, you can feel valued again.”

She considers it an honor to be able to share that with her father.

A former inspector in the Suffolk County Police Department and a commander of homicide, Mueller’s father has a well-known sweet tooth.

When she visits, Mueller brings an iced coffee with hazelnut syrup and half and half, a crumb cake, croissant or donut. “He’s in seventh heaven,” she said.

When he sees his family, his face “lights up,” said Mueller. 

“Even if the memories of our visit is fleeting, for those moments in time, he’s a devoted father and a valued father and grandfather who still feels our love.”

Sleep may help the brain remove waste, such as those all-too-dangerous beta-amyloid plaques linked to Alzheimer's disease. METRO photo
A few extra ZZZs can help clear brain clutter

By David Dunaief, M.D.

Dr. David Dunaief

Cognitive loss, or mental decline, is a common concern as we age. So much so that a cottage industry of app-based games has sprouted to help keep our brains sharp.

What do we know about the brain, really, though? Startlingly little. We do know that certain drugs, head injuries and lifestyle choices have negative effects, along with numerous neurological, infectious, and rheumatologic disorders and diseases.

Some, like dementia, Parkinson’s, and strokes, are recognized for some of their effects on the brain. However, others – lupus, rheumatoid arthritis, psychiatric mood disorders, diabetes and heart disease – also can have long-term effects on our brains.

These disorders generally have three signs and symptoms in common: they cause either altered mental status, physical weakness, or mood changes — or a combination of these.

Of course, addressing the underlying medical disorder is critical. Fortunately, several studies also suggest that we may be able to help our brains function more efficiently and effectively with rather simple lifestyle changes: sleep, exercise and possibly omega-3s.

How does brain clutter affect us?

Are 20-somethings sharper and more quick-witted than those over 60?

German researchers put this stereotype to the test and found that educated older people tend to have a larger mental database of words and phrases to pull from since they have been around longer and have more experience (1). When this is factored into the equation, the difference in terms of age-related cognitive decline becomes negligible.

This study involved data mining and creating simulations. It showed that mental slowing may be at least partially related to the amount of clutter or data that we accumulate over the years. The more you know, the harder it becomes to come up with a simple answer to something.

What if we could reboot our brains, just like we do a computer or smartphone? This may be possible through sleep, exercise and omega-3s.

Why does sleep help?

Why should we dedicate a large chunk of our lives to sleep? Researchers have identified a couple of specific values we receive from sleep: one involves clearing the mind, and another involves productivity.

For the former, a study done in mice shows that sleep may help the brain remove waste, such as those all-too-dangerous beta-amyloid plaques (2). When we have excessive plaque buildup in the brain, it may be a sign of Alzheimer’s. When mice were sleeping, the interstitial space (the space between brain gyri, or structures) increased by as much as 60 percent.

This allowed the lymphatic system, with its cerebrospinal fluid, to clear out plaques, toxins and other waste that had developed during waking hours. With the enlargement of the interstitial space during sleep, waste removal was quicker and more thorough, because cerebrospinal fluid could reach much farther into the spaces. A similar effect was seen when the mice were anesthetized.

In an Australian study, results showed that sleep deprivation may have contributed to an almost one percent decline in gross domestic product (3). Why? When people don’t get enough sleep, they are not as productive. They tend to be more irritable, and their concentration may be affected. While we may be able to turn on and off sleepiness on short-term basis, we can’t do this continually.

According to the Centers for Disease Control and Prevention, 4.2 percent of respondents reported having fallen asleep in the prior 30 days behind the wheel of a car during a 2009-2010 study (4). Most commonly, these respondents also reported getting usual sleep of six hours or fewer, snoring, or unintentionally falling asleep during the day. “Drowsy driving” led to 91,000 car crashes in 2017, according to estimates from the National Highway Traffic Safety Administration (5).

How does exercise help your brain?

One study with rats suggests that a lack of exercise can cause unwanted new brain connections. Rats that were not allowed to exercise were found to have rewired neurons around their medulla, the part of the brain involved in breathing and other involuntary activities. This included more sympathetic (excitatory) stimulus that could lead to increased risk of heart disease (6). 

Among the rats allowed to exercise regularly, there was no unusual wiring, and sympathetic stimuli remained constant. This may imply that being sedentary has negative effects on both the brain and the heart. We need human studies to confirm this impact.

Omega-3 fatty acids may affect brain volume

In the Women’s Health Initiative Memory Study of Magnetic Resonance Imaging Study, results showed that those postmenopausal women who were in the highest quartile of omega-3 fatty acids had significantly greater brain volume and hippocampal volume than those in the lowest quartile (7). The hippocampus is involved in memory and cognitive function.

Specifically, the researchers looked at the levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in red blood cell membranes. The source of the omega-3 fatty acids could have been either from fish or from supplementation.

It’s never too late to improve brain function. Although we have a lot to learn about the functioning of the brain, we know that there are relatively simple ways we can positively influence it.

References:

(1) Top Cogn Sci. 2014 Jan.;6:5-42. (2) Science. 2013 Oct. 18;342:373-377. (3) Sleep. 2006 Mar.;29:299-305. (4) cdc.gov. (5) nhtsa.gov. (6) J Comp Neurol. 2014 Feb. 15;522:499-513. (7) Neurology. 2014;82:435-442.

Dr. David Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com or consult your personal physician.