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Tag: Alzheimer

  • A novel, powerful tool to unveil the communication between gut microbes and the brain

    A novel, powerful tool to unveil the communication between gut microbes and the brain

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    Newswise — In the past decade, researchers have begun to appreciate the importance of a two-way communication that occurs between microbes in the gastrointestinal tract and the brain, known as the gut–brain axis. These “conversations” can modify how these organs work and involve a complex network of microbe- and brain-derived chemical signals that are challenging for scientists to decouple in order to gain an understanding.

    “Currently, it is difficult to determine which microbial species drive specific brain alterations in a living organism,” said first author, Dr. Thomas D. Horvath, instructor of pathology and immunology at Baylor College of Medicine and Texas Children’s Hospital. “Here we present a valuable tool that enables investigations into connections between gut microbes and the brain. Our laboratory protocol allows for the identification and comprehensive evaluation of metabolites – compounds microbes produce – at the cellular and whole-animal levels.”

    The gastrointestinal tract harbors a rich, diverse community of beneficial microorganisms collectively known as the gut microbiota. In addition to their roles in maintaining the intestinal environment, gut microbes are increasingly being recognized for their influence on other distant organs, including the brain.

    “Gut microbes can communicate with the brain through several routes, for example by producing metabolites, such as short-chain fatty acids and peptidoglycans, neurotransmitters, such as gamma-aminobutyric acid and histamine, and compounds that modulate the immune system as well as others,” said co-first author Dr. Melinda A. Engevik, assistant professor of regenerative and cellular medicine at the Medical University of South Carolina.

    The role microbes play in the health of the central nervous system is highlighted by the links between the gut microbiome and anxiety, obesity, autism, schizophrenia, Parkinson’s disease and Alzheimer’s disease.

    “Animal models have been paramount in linking microbes to these fundamental neural processes,” said co-author Dr. Jennifer K. Spinler, assistant professor of pathology and immunology at Baylor and the Texas Children’s Hospital Microbiome Center. “The protocol in the current study enables researchers to take steps toward unraveling the specific involvement of the gut-brain axis in these conditions, as well as its role in health.”

    A road map to understand the complex traffic system in the gut-brain axis

    One strategy the researchers used to gain insight into how a single type of microbe can influence the gut and the brain consisted of growing the microbes in the lab first, collecting the metabolites they produced and analyzing them using mass spectrometry and metabolomics. Mass spectrometry is a laboratory technique that can be used to identify unknown compounds by determining their molecular weight and to quantify known compounds. Metabolomics is a technique for the large-scale study of metabolites.

    “The effect of metabolites was then studied in mini-guts, a laboratory model of human intestinal cells that retains properties of the small intestine and is physiologically active,” Engevik said. “In addition, the microbe’s metabolites can be studied in live animals.”

    “We can expand our study to a community of microbes,” Spinler said. “In this way we investigate how microbial communities work together, synergize and influence the host. This protocol gives researchers a road map to understand the complex traffic system between the gut and the brain and its effects.”

    “We were able to create this protocol thanks to large interdisciplinary collaborations involving clinicians, behavioral scientists, microbiologists, molecular biology scientists and metabolomics experts,” Horvath said. “We hope that our approach will help to create designer communities of beneficial microbes that may contribute to the maintenance of a healthy body. Our protocol also offers a way to identify potential solutions when miscommunication between the gut and the brain leads to disease.”

    Read all the details of this work in Nature Protocols.

    Other contributors to this work included Sigmund J. Haidacher, Berkley Luck, Wenly Ruan, Faith Ihekweazu, Meghna Bajaj, Kathleen M. Hoch, Numan Oezguen, James Versalovic and Anthony M. Haag. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, Texas Children’s Hospital and Alcorn State University.

    This study was supported by an NIH K01 K12319501 grant and Global Probiotic Council 2019-19319, grants from the National Institute of Diabetes and Digestive and Kidney Diseases (Grant P30-DK-56338 to Texas Medical Center Digestive Disease Center, Gastrointestinal Experimental Model Systems), NIH U01CA170930 grant and unrestricted research support from BioGaia AB (Stockholm, Sweden).

    Read about novel findings on the gut–brain axis discovered using this protocol, in iScience, Biomolecules and Cell and Molecular Gastroenterology and Hepatology.

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    Baylor College of Medicine

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  • 6 Minutes of Exercise May Help Shield Your Brain From Alzheimer’s

    6 Minutes of Exercise May Help Shield Your Brain From Alzheimer’s

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    By Cara Murez 

    HealthDay Reporter

    THURSDAY, Jan. 12, 2023 (HealthDay News) — Six minutes of high-intensity exercise might prolong the lifespan of a healthy brain, perhaps delaying the start of Alzheimer’s and Parkinson’s diseases, a new, small study suggests.

    Researchers found that short but intense cycling increased the production of a protein called brain-derived neurotrophic factor (BDNF), which is essential for brain formation, learning and memory. It’s thought that BDNF might protect the brain from age-related mental decline.

    “BDNF has shown great promise in animal models, but pharmaceutical interventions have thus far failed to safely harness the protective power of BDNF in humans,” said lead study author Travis Gibbons, from the University of Otago in New Zealand.

    “We saw the need to explore non-pharmacological approaches that can preserve the brain’s capacity which humans can use to naturally increase BDNF to help with healthy aging,” Gibbons said.

    The report was published Jan. 11 in the Journal of Physiology.

    BDNF promotes the brain’s ability to form new connections and pathways, and also helps neurons survive. Animal studies have shown that increasing the availability of BDNF boosts cognitive performance, such as thinking, reasoning or remembering.

    For this study, the researchers wanted to look at the influence of fasting and exercise on BDNF production in humans. 
     

    Working with a dozen men and women, the investigators compared fasting, low-intensity cycling for 90 minutes, six-minute high-intensity cycling, and a combination of fasting and exercise.

    Brief but vigorous exercise was the most efficient way to increase BDNF compared to one day of fasting with or without lengthy, low-intensity exercise, the researchers said.

    BDNF increased four to five times more compared to fasting, which showed no BDNF change, or prolonged activity, which showed a slight increase in BDNF.

    More work is needed to better understand these findings, the study authors noted.

    The researchers hypothesize that the brain switches its favored fuel source for another to meet the body’s energy demands. This could mean metabolizing lactate instead of glucose during exercise, which potentially could initiate pathways that lead to more BDNF in the blood.

    The BDNF boost could be due to an increased number of blood platelets, which store large amounts of BDNF. This is more heavily influenced by exercise than fasting, they explained.

    Ongoing research will further study the effects of calorie restriction and exercise.

    “We are now studying how fasting for longer durations, for example up to three days, influences BDNF,” Gibbons said in a journal news release. “We are curious whether exercising hard at the start of a fast accelerates the beneficial effects of fasting. Fasting and exercise are rarely studied together. We think fasting and exercise can be used in conjunction to optimize BDNF production in the human brain.”

    More information
     

    The U.S. National Library of Medicine has more on BDNF.

     

    SOURCE: Journal of Physiology, news release, Jan. 11, 2023

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  • What to Know About Newly Approved Alzheimer’s Drug

    What to Know About Newly Approved Alzheimer’s Drug

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    Jan. 6, 2023 — The highly anticipated Alzheimer’s drug lecanemab was granted accelerated approval status this afternoon by the FDA, offering hope where there has been little for patients and their families affected by the devastating disease.

    More than 6 million people in the U.S. live with Alzheimer’s.

    It’s not a cure, but the drug, given intravenously every 2 weeks, has shown moderate positive effects in clinical trials in slowing early-stage disease.

    But many are wary. As explained in an editorial last month in the journal The Lancet, “The Alzheimer’s disease community has become accustomed to false hope, disappointment, and controversy.”

    Some worry about lecanemab’s safety as some people in clinical trials experienced serious side effects of bleeding and swelling in the brain. Scientists recently attributed a third death to lecanemab, brand name Leqembi, though the drugmaker disputed the medication was the cause.

    So what should patients and their families make of today’s news? Here we answer some of the top questions surrounding the drug.

    What Does Today’s FDA Action Mean?

    The FDA granted accelerated approval to Leqembi after it showed positive trial results in slowing the progression of early-stage disease. 

    The FDA can grant accelerated approval for drugs that treat serious conditions and fill an unmet medical need while drugs continue to be studied in larger trials.

    With the FDA approval in hand, doctors can now prescribe the medication.

    Rebecca Edelmayer, PhD, the Alzheimer’s Association senior director of scientific engagement, says that with the FDA’s move today, ramping up manufacturing — and eventually nationwide distribution and implementation — will take some time. 

    “Ask your doctor about availability,” she says. “The main issue is that, without insurance and Medicare coverage of this class of treatments, access for those who
    could benefit from the newly approved treatment will only be available to those who can pay out-of-pocket. Without coverage, people simply won’t be able to get the treatment.”

    The Washington Post reports that with accelerated approval, drugmaker Eisai is expected to immediately apply for full FDA approval, which wouldn’t be likely to come before later this year. Full approval could help clear the path for Medicare coverage of the drug.

    Potential Benefit?

    Those who got Leqembi in a clinical trial for 18 months experienced 27% less decline in memory and thinking relative to the group who got a placebo. It also reduced amyloid in the brain, the sticky protein that builds up in the brains of people with Alzheimer’s and is considered a hallmark of the disease.

    Howard Fillit, MD, co-founder and chief science officer of the Alzheimer’s Drug Discovery Foundation, says, “It’s the first phase III study in our field of a disease-modifying drug where the clinical efficacy was very clear.”

    Concerns About Side Effects

    The drug has raised safety concerns as it has been linked with certain serious adverse events, including brain swelling and bleeding. In the trial, 14% of patients who received the drug experienced side effects that included brain swelling and bleeding, compared to about 11% in the placebo group.

    Scientists have reportedly linked three deaths during the clinical trial to lecanemab, though it is unclear whether it caused the deaths. 

    Fillit notes that the first two people who died were on blood thinners when they received lecanemab. 

    “There are things about the use of the drug in the real world that we need to work out, especially in the context of people with comorbidities,” he says.

    The third death is a little different, Fillit says. The patient, who had a stroke, showed signs of vasculitis, or inflammation of the blood vessels.

    “We don’t know exactly what happened, but we do know it was very, very rare” among the people involved in the trials, he says.

    Edelmayer says that the most common reported side effects during the trials were infusion-related reactions, headache, and amyloid-related imaging abnormalities (ARIA). According to the FDA, these abnormalities “are known to occur with antibodies of this class. ARIA usually does not have symptoms, although serious and life-threatening events rarely may occur.”

    The FDA has added these as warnings to the drug’s label, describing the possible infusion-related reactions as flu-like symptoms, nausea, vomiting, and changes in blood pressure.
    How Much Will It Cost?

    Eisai says that lecanemab will cost $26,500 a year.

    In a draft report released in December, the Institute for Clinical and Economic Review (ICER) said a price ranging from $8,500 to $20,600 a year would make the drug cost-effective. While the group has no authority to set prices, many large health insurers consider its reports when they negotiate prices and some drugmakers take into account ICER’s recommendations when setting prices.

    An editorial in The Lancet last month warns that the cost will likely be “prohibitive” for low- and middle-income countries and many health systems don’t have the infrastructure for a widespread rollout.

    Will Medicare Cover it?

    The Centers for Medicare and Medicaid Services (CMS), which runs Medicare, which covers most people with Alzheimer’s, has indicated it won’t broadly cover amyloid-lowering drugs until the drug gets full U.S. approval based on clinical benefits, as opposed to accelerated approval.

    That means people would have to pay thousands out of pocket at first to get it.

    The CMS decision effectively denies Medicare coverage of fast-tracked FDA-approved medications for Alzheimer’s disease unless the person is enrolled in an approved clinical trial. 

    On Dec. 19, the Alzheimer’s Association filed a formal request asking CMS to remove the trial-only requirement and provide full and unrestricted coverage for FDA-approved Alzheimer’s treatments.

    CMS says in a statement after today’s announcement: “Because Eisai’s product, lecanemab, was granted accelerated approval by the FDA, it falls under CMS’s existing national coverage determination. CMS is examining available information and may reconsider its current coverage based on this review.”

    “If lecanemab subsequently receives traditional FDA approval, CMS would provide broader coverage,” the statement says.

    Who Benefits Most From This Drug?

    Lecanemab is a treatment for people with early-stage Alzheimer’s disease who have amyloid in their brain. This means people with other types of dementia, or those in the later stages of Alzheimer’s disease, are not likely to improve with this drug.

    Who Makes Lecanemab?  

    Japan-based Eisai is developing the drug, a monoclonal antibody, in collaboration with the U.S. company Biogen.

    What’s the Alzheimer’s Association’s View?

    The association urged accelerated FDA approval. In a statement, it says it “welcomes and is further encouraged” by the clinical trial results. 

    It says data published in the New England Journal of Medicine confirms lecanemab “can meaningfully change the course of the disease for people in the earliest stages of Alzheimer’s disease.”

    “We are energized at the progress we are seeing in the research pipeline. The science is telling us that although anti-amyloid treatments are not a cure — they are not going to be the end of
    treating Alzheimer’s — they are certainly the beginning,” Edelmayer says.
    Are There Alternatives? 

    The FDA gave accelerated approval to Biogen to produce another drug for Alzheimer’s, Aduhelm (aducanemab), in 2021, but the move was controversial as the drug’s effectiveness was widely questioned. It has since largely been pulled from the market. 

    Aduhelm had been the first approved early-stage Alzheimer’s treatment since 2003.

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  • U-M Health neurologists available to discuss Lecanemab, Alzheimer’s drug FDA approval #lecanemab #alzheimers

    U-M Health neurologists available to discuss Lecanemab, Alzheimer’s drug FDA approval #lecanemab #alzheimers

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    Newswise — The U.S. Food and Drug Administration granted accelerated approval Friday for lecanemab, an Alzheimer’s disease drug for which studies showed the promising biological effect of removal of the brain’s amyloid buildup that occurs in the disease.

    University of Michigan Health, Michigan Medicine, has experts available to talk about the accelerated approval and what it could mean for the future of patient care for Alzheimer’s.

    Available:

    Judith Heidebrink, M.D. – Neurologist and Clinical Core Co-Lead of the Michigan Alzheimer’s Disease Center

    “While lecanemab is not a cure for Alzheimer’s disease, it could help someone with mild Alzheimer’s symptoms maintain their independence for a longer period of time. There are side effects, and, in some cases, the risk of side effects will outweigh the potential benefit. So, as with all drug treatments, the risks and benefits must be considered carefully for each individual patient. Lecanemab’s potential side effects include brain swelling and/or bleeding, so anyone treated with it will need close monitoring, including MRI scans to look for side effects.

    We do not know if lecanemab can help someone with more advanced Alzheimer’s symptoms because the studies have focused on early symptoms. However, there are reasons to believe that a benefit is unlikely with more advanced disease. Could lecanemab prevent symptoms of Alzheimer’s disease if given to someone at risk? We don’t know yet, but we are excited to be participating in a study that will help answer that question, the AHEAD 3-45 study.”

    Henry Paulson, M.D., Ph.D. – Neurologist and Director of the Michigan Alzheimer’s Disease Center

    “Alzheimer’s disease is a complex disorder, with many factors contributing to its progressive course, one of them being amyloid. The slowing of disease symptoms by lecanemab argues that targeting amyloid is a viable treatment strategy. While lecanemab doesn’t represent a cure, it gives me hope that we are now reaching the era of disease-modifying treatments for dementia.”

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    Michigan Medicine – University of Michigan

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  • Check Older Relatives for Signs of Dementia This Holiday Season

    Check Older Relatives for Signs of Dementia This Holiday Season

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    Dec. 12, 2022 – Betsy E., a 58-year-old editor in Delaware, was looking forward to seeing her 79-year-old aunt for Thanksgiving. It had been almost 3 years since they last saw each other, because holiday plans had been canceled due to the COVID-19 pandemic.

    “I had kept in touch with Aunt Vera by phone, and she was conversational,” says Betsy, who asked that her real name not be used for this article. “She always had a tendency to repeat herself, so I didn’t think much of it when she repeated the same stories as if I had never heard them.”

    But when Betsy arrived at her aunt’s, she was “shocked.” There was moldy food in the fridge. A stack of dust-covered library books stood in the hallway, some due over 6 months ago. Usually Aunt Vera cooked a lavish Thanksgiving dinner, but this year, she said she didn’t know what to cook and suggested going to a restaurant.

    Monica Moreno, the senior director of care and support at the Alzheimer’s Association, says the holiday season “is often a time when families come together. It may also be a time when extended family members notice cognitive changes in a loved one they don’t see regularly.”

    Even if you often talk by phone, “it’s not the same as seeing firsthand how the person is navigating daily life,” Moreno notes.

    Red Flags 

    Two officials from Brightview Senior Living – an organization of 45 senior communities across the United States– echo Moreno. 

    Patrick Doyle, PhD, the corporate director of dementia care for Brightview and principal faculty at the Johns Hopkins Center for Innovative Care in Aging, and Cole Smith, the director of dementia care at Brightview, say it’s important “to acknowledge that each person has a different baseline for cognitive health” and to “use your knowledge of your relative to understand when their behavior is out of the norm for them.”

    For example, some people seem to recall every name, date, and number they’ve ever learned. For them, not remembering their grandchild’s birthday would be “exceptionally unusual.” 

    Short-term memory declines with aging, but people in the early stages of Alzheimer’s disease “often experience memory loss to an extent that it begins to disrupt their daily life,” say Doyle and Smith. “The individual may be missing important events, forgetting to take medications they have taken for many years, or they may even be starting to mix up names and details about their friends and family.”

    Another common warning sign is that the person may have a hard time doing familiar tasks. 

    “Often, people with early stages of [Alzheimer’s] may get lost driving or walking to routine places,” they say. 

    Other warning signs include:

    • Recent traffic violations, accidents, or dents and damage to the car
    • Reluctance to walk usual distances
    • Changes in personal hygiene
    • Missed medical appointments
    • Changes in financial habits (for example, missing bills)
    • Changes in sleep habits
    • Decrease in usual standard of housekeeping
    • Scorched pots or pans
    • Confusion with time or place
    • New problems with spoken or written words 
    • Misplacing objects
    • Changes in mood or personality
    • Social withdrawal
    • A hard time following recipes or doing other complex tasks
    • Forgetting names of friends or family 
    • Trouble understanding visual images
    • A hard time retracing steps
    • Diminished or poor judgment

    Starting a Conversation

    Don’t dismiss your relative’s symptoms, Doyle and Smith urge. “There is a lot of fear associated with  [Alzheimer’s], and this can cause people to try to rationalize the observed behavior as normal, when it is a clear deviation from the person’s norm.”

    Instead, “jump into action” if you’re concerned – although it can be a “delicate subject, so proceed with caution.” 

    Use your knowledge of your relative to determine how they will likely respond when you broach the subject. 

    “Some people experiencing cognitive decline are aware, and will make statements about their own observations and concerns; in that case, offer your support and get a thorough clinical assessment,” they say. 

    Moreno also  recommends talking to other family members before sharing concerns. 

    “Ask if others are noticing the same signs you see.” Some family members may dismiss the changes, saying they’re a part of normal aging; and spouses may “cover for one another,” she warns.

    ‘Be Honest and Compassionate 

    “When it comes to what to say, be honest and compassionate,” Moreno advises. “Start by sharing some of the things you’re seeing and asking if your loved one is also concerned. ‘Mom, I noticed you were having a hard time making holiday cookies and I’d like to talk to you about why that happened. You’ve been making them for years and it’s not like you.’” 

    Moreno recommends focusing on specifics and sharing them in a way you think the family member will be able to hear. “Let them know you’ve got their back.” And if your first attempt doesn’t go as well as you would have liked, “take time to regroup. You might try a different time of day or recruit someone else to talk to your loved one” like another family member, friend, or trusted person from their faith community. You can also share your concerns with the person’s doctor.

    Doyle and Smith note that some people living with dementia “do not have an awareness of their deficits and may even be offended by the suggestion that something is wrong, making a conversation about your concerns more challenging and delicate.”

    If you have a strong relationship with your relative, “you can leverage that connection by asking the person if they can ‘do you a favor’ – share that you are concerned about their health and say it would make you feel more comfortable if they went with you to see a doctor.”

    And avoid “coming across as accusatory or demanding.” People “respond better to compassion, care, and support,” Doyle and Smith observe, stressing that there is “no one approach that works for everyone,” since “every person is unique, and family dynamics vary dramatically.” 

    The Alzheimer’s Association’s 24/7 hotline provides advice and guidance (800-272-3900) and its website offers conversation tips to help families navigate this delicate process. 

    As for Betsy, after noticing her aunt was not herself, she decided to contact  her aunt’s son.

    “There had been some estrangement, and my cousin hadn’t seen my aunt for a long time. But once he heard what was going on, it motivated him to want to heal things with her, go to the doctor with her, and make a plan with her for her future, so he’s coming for Christmas.” 

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  • Dementia Has Turned My Family’s World Upside Down, And I Don’t Know How Much More I Can Take

    Dementia Has Turned My Family’s World Upside Down, And I Don’t Know How Much More I Can Take

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    My oldest sister, Abby, calls for the second time this morning. “Oh, Jannie!” she says, reverting to my baby-sister nickname. “It’s so great to hear your voice, finally! Are you in Idaho now?”

    “We sure are,” I answer, in the same tone that I answered the same question earlier. It’s been over a year since I relocated, not long after I helped Abby and her husband transition to assisted living. I can picture her perched on the loveseat in their tiny apartment, its walls vivid with her paintings, sun streaming in from windows that look out over California foothills. “How are you guys?” I ask.

    “Oh, fine! We just got back from … where we eat.” She means the dining room, but she falters. Then, brightening: “Are you in Idaho now?”

    Our conversations circle like this now, their loops gradually shortening, spiraling cheerfully along the surface.

    According to Alzheimer’s Association, Abby is one of 6.5 million Americans living with the disease. When she was diagnosed, I was heartsick. One of the few consolations I clung to was that my other sister, Sal, and I could sustain each other through the long goodbye.

    But it turns out that Alzheimer’s is not the only type of dementia. Others include dementia with Lewy bodies, vascular dementia and Huntington’s disease. There are other conditions that cause mental confusion or disorientation, sometimes temporarily, as can occur in older people who have urinary tract infections. With other afflictions, dementia is permanent and progressive. One such disorder is corticobasal degeneration. I discovered that when Sal, my next-oldest sister, was diagnosed.

    Growing up, I was the baby of the family. Abby, 12 years my senior, was for me the embodiment of glamour. Sal, seven years older than me, was my mentor and de facto nanny. I dogged both my big sisters’ steps as much as they’d let me, observing them with a mixture of envy and hero worship. I reveled in their attention when they would dress me up like a life-size doll, until I grew restless and they’d hiss at me to “hold still!” Other times, when they thought I was getting off too easily for whatever annoyance I’d caused, they’d take me out of Mom’s earshot and scold me themselves. It worked: my sisters were my role models, and I craved their approval more than I did that of my parents or, later, even my friends.

    I thought Abby could do anything. Sidestepping our domineering father, she put herself through college, becoming an artist and teacher. I was five when she left home, and our house felt semi-becalmed in her absence.

    After Abby left, Sal did nearly as much to raise me as did my mother, who so often deflated in the face of my father’s vehemence. It was Sal who taught me how to clean a bathroom, how to bake a cake, how to be a good friend, and how to drive her ’67 Camaro the summer I turned 16 and she was home for a visit. Later, as the three of us were figuring out how to raise our sons — coming from a family of all girls, we were somewhat mystified as we produced only boys — it was Sal’s house where we gathered for holidays and celebrations, for the memorials when our parents died.

    Abby was in her mid-60s when her formidable mind showed signs of slipping. It took years, several fraught family meetings, and a long series of neurological assessments before Sal and I, along with the rest of Abby’s loved ones, had to face the reality of her condition. Like many people, we’d been schooled to believe that Alzheimer’s was something to be dreaded, a fate possibly worse than death.

    As devastated as we both were about Abby, Sal was confronted with another life cataclysm when her 40-year marriage blew up. It turned out her steady, taciturn husband had been a serial philanderer for a dozen years. She emerged shaken and raw, as though whatever emotional insulation she’d had was wearing away, leaving her newly fragile.

    Then one day I got a frantic call from the closest in Sal’s large circle of friends. “Something’s wrong,” the friend said. “Come see for yourself.”

    I still lived in California at the time, 300 miles up the coast from where Sal lived. I drove down the next day. Sal greeted me at her front door, delighted to see me but startlingly thin. Her posture was hunched, her left arm contracted at an odd angle. A bruise, unsuccessfully disguised with makeup, spread across one side of her face.

    “I had a little fall down the stairs,” she explained with a nervous laugh. “It’s not a big deal, nothing’s broken.” Her affect as well as her body seemed so frail that I kept my alarm to myself, but after our visit I conferred with her oldest son, who lived nearby. He too was concerned. He’d recently taken her out to her favorite steak place, where she’d had no idea that she’d rested her left arm in the middle of her entree until he pointed it out to her.

    It took months for Sal to get appointments with a battery of neurologists, and even longer for the doctors to confer. Eventually, they agreed on a diagnosis. All the signs pointed to corticobasal degeneration, sometimes referred to as corticobasal syndrome.

    I’d never heard of either. “Is that serious?” I asked Sal when she told me.

    “It’s not good,” she answered. “But I’m going to make the best of it.” Her voice trembled with mixed fear and resolve, already weaker than it had been a few months earlier. “I’ll be OK,” she said. My heart cracked, understanding for the first time that she wouldn’t be.

    “’Is that serious?’ I asked Sal when she told me. ‘It’s not good,’ she answered. ‘But I’m going to make the best of it.’ Her voice trembled with mixed fear and resolve, already weaker than it had been a few months earlier.”

    I didn’t want to plague Sal with questions, so I pored over what little information I could find. What I learned is that the best to be said of corticobasal degeneration is that it is rare. It blights the brain’s cortex and basal ganglia, causing loss of balance and muscle control, impaired speech, the eerie “alien limb syndrome” — which explained how Sal’s arm wound up in her prime rib — and, as the literature blandly stated, “changes in thinking and personality.” It is progressive, incurable, and, unlike Alzheimer’s or Parkinson’s, no medication exists that slows it down. Ultimately, it is fatal. I wanted to creep into a cave, a refuge where I could process this new upheaval.

    But Abby, once she’d learned that Sal was ailing, had many questions — rather, the same questions over and over, with which she besieged Sal over the phone. As the suddenly most capable sister, it fell to me to deflect her well-meaning assaults.

    “What’s the name of what she’s got? Let me write it down,” Abby would ask every time we talked. Her refrigerator fluttered with Post-its, all of them with the name of Sal’s malady as I’d dictated it, inscribed in Abby’s graceful script.

    Abby was as determined to fix Sal as she was unable. She obsessed over her scheme to move in with her now-disabled sister, leaving her husband — never able to countermand Abby’s will — at home. Sal was aghast but had neither the energy nor the temperament to head Abby off.

    Again, intervention fell to me. It demanded new skills, including therapeutic lying, as I invented reasons why the upcoming week wouldn’t be a good time for Abby to go stay with Sal, week after week, month after month.

    These days, so long as I don’t bring up Sal and her illness when we visit, Abby seems happy. Her body is strong, she can draw and paint, and thanks to her devoted husband, she doesn’t require the kind of memory care that is designed to both protect and restrict patients who are prone to wandering. She loves her new home, including the dining room where, as far as she’s concerned, the menu changes with every meal. It’s possible that Abby is more content now than she was when her brain was firing on all its cylinders.

    Sal’s decline, by comparison, is cruel. I’ve helped her son move her to upgraded care three times as she has diminished. Her current facility is the best available in her area, providing round-the-clock care. She can summon help with the push of a button on a lanyard around her neck. But she has so little control over her limbs now that sometimes she can’t find the button, or she pushes the TV remote instead. She can no longer walk, stand or sit up unaided. She insists on feeding herself but it’s difficult to watch; choking is always a danger. Her speech has further weakened, her words slurred and halting to the point where they’re often indecipherable.

    I travel to visit her, and within minutes of my arrival she makes plaintive requests, as poignant for their simplicity as they are unrealistic.

    “Can you bring me my sewing machine? What if we hop in your car and go to lunch?” she asks, her blue eyes wide with hope. The disease’s assault on her brain leaves her unable to register the scope of her disability or relinquish her identity as someone who can operate a sewing machine or hop in a car. It’s a symptom that causes more distress — for her, for her caregivers, for her loved ones — than her physical limitations.

    I manage to change the subject every time, and we laugh together over the stories she recounts from our childhood. But soon she tires, her eyes unfocused and half-shut, her words devolving into incoherent mumbling. Still, she continues talking on and on. Ashamed of my limited patience, I find an excuse to leave, assuring her I’ll return soon.

    I don’t talk much about this. Chronic, long-lasting tragedy is unnerving; nobody knows what to say in response to my stories. Friends tell me I’m strong, that I’m handling it well. I am not, I want to say but don’t: I’m a lost little sister wandering the shores of calamity.

    But I’m no longer the baby of the family, so I must do what I can. For Abby, I can meet her where she is, revisiting each topic or question however she reframes and repeats it, again and again. For Sal, I can hang on a little longer when I can’t understand a word she says, or when her descent is so dizzying it makes me want to escape rather than bear witness to it.

    In my weaker moments, I fret over an unanswerable question: will my brain fail me too? I don’t often allow myself to go there. My sisters’ dementias have flipped our birth order, and it’s now my place to be the steady one, the big sister among us, for whatever time we have left together.

    Jan M. Flynn’s essays appear on Medium.com and on her blog at JanMFlynn.net. Her short fiction has won international awards and appears in literary journals including Midnight Circus, The Binnacle, Noyo River Review, Far Side Review, Grim and Gilded, and Bullshit Lit as well as anthologies. She is also the host and producer of a weekly podcast, “Here’s A Thought,” for people who overthink. She lives in Boise, Idaho, and is represented by Helen Adams of Zimmermann Literary, New York.

    Do you have a compelling personal story you’d like to see published on HuffPost? Find out what we’re looking for here and send us a pitch.

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  • How Your Voice Could Reveal Hidden Disease

    How Your Voice Could Reveal Hidden Disease

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    Dec. 7, 2022 – Most of us have two voice changes in our lifetime: first during puberty, as the vocal cords thicken and the voice box migrates down the throat. Then a second time as aging causes structural changes that may weaken the voice. 

    But for some of us, there’s another voice shift, when a disease begins or when our mental health declines. 

    This is why more doctors are looking into voice as a biomarker – something that tells you that a disease is present. 

    Vital signs like blood pressure or heart rate “can give a general idea of how sick we are. But they’re not specific to certain diseases,” says Yael Bensoussan, MD, director of the University of South Florida’s Health Voice Center and the co-principal investigator for the National Institutes of Health’s Voice as a Biomarker of Health project. 

    “We’re learning that there are patterns” in voice changes that can indicate a range of conditions, including diseases of the nervous system and mental illnesses, she says. 

    Speaking is complicated, involving everything from the lungs and voice box to the mouth and brain. “A breakdown in any of those parts can affect the voice,” says Maria Powell, PhD, an assistant professor of otolaryngology (the study of diseases of the ear and throat) at Vanderbilt University in Nashville, who is working on the NIH project. 

    You or those around you may not notice the changes. But researchers say voice analysis as a standard part of patient care – akin to blood pressure checks or cholesterol tests – could help identify those who need medical attention earlier. 

    Often, all it takes is a smartphone – “something that’s cheap, off-the-shelf, and that everyone can use,” says Ariana Anderson, PhD, director of UCLA’s Laboratory of Computational Neuropsychology. 

    “You can provide voice data in your pajamas, on your couch,” says Frank Rudzicz, PhD, a computer scientist for the NIH project. “It doesn’t require very complicated or expensive equipment, and it doesn’t require a lot of expertise to obtain.” Plus, multiple samples can be collected over time, giving a more accurate picture of health than a single snapshot from, say, a cognitive test. 

    Over the next 4 years, the Voice as a Biomarker team will receive nearly $18 million to gather a massive amount of voice data. The goal is 20,000 to 30,000 samples, along with health data about each person being studied. The result will be a sprawling database scientists can use to develop algorithms linking health conditions to the way we speak.

    For the first 2 years, new data will be collected exclusively via universities and high-volume clinics to control quality and accuracy. Eventually, people will be invited to submit their own voice recordings, creating a crowdsourced dataset. “Google, Alexa, Amazon – they have access to tons of voice data,” says Bensoussan. “But it’s not usable in a clinical way, because they don’t have the health information.” 

    Bensoussan and her colleagues hope to fill that void with advance voice screening apps, which could prove especially valuable in remote communities that lack access to specialists or as a tool for telemedicine. Down the line, wearable devices with voice analysis could alert people with chronic conditions when they need to see a doctor. 

    “The watch says, ‘I’ve analyzed your breathing and coughing, and today, you’re really not doing well. You should go to the hospital,’” says Bensoussan, envisioning a wearable for patients with COPD. “It could tell people early that things are declining.” 

    Artificial intelligence may be better than a brain at pinpointing the right disease. For example, slurred speech could indicate Parkinson’s, a stroke, or ALS, among other things. 

    “We can hold approximately seven pieces of information in our head at one time,” says Rudzicz. “It’s really hard for us to get a holistic picture using dozens or hundreds of variables at once.” But a computer can consider a whole range of vocal markers at the same time, piecing them together for a more accurate assessment.

    “The goal is not to outperform a … clinician,” says Bensoussan. Yet the potential is unmistakably there: In a recent study of patients with cancer of the larynx, an automated voice analysis tool more accurately flagged the disease than laryngologists did. 

    “Algorithms have a larger training base,” says Anderson, who developed an app called ChatterBaby that analyzes infant cries. “We have a million samples at our disposal to train our algorithms. I don’t know if I’ve heard a million different babies crying in my life.” 

    So which health conditions show the most promise for voice analysis? The Voice as a Biomarker project will focus on five categories.

    Voice Disorders 

    (Cancers of the larynx, vocal fold paralysis, benign lesions on the larynx)

    Obviously, vocal changes are a hallmark of these conditions, which cause things like breathiness or “roughness,” a type of vocal irregularity. Hoarseness that lasts at least 2 weeks is often one of the earliest signs of laryngeal cancer. Yet it can take months – one study found 16 weeks was the average – for patients to see a doctor after noticing the changes. Even then, laryngologists still misdiagnosed some cases of cancer when relying on vocal cues alone. 

    Now imagine a different scenario: The patient speaks into a smartphone app. An algorithm compares the vocal sample with the voices of laryngeal cancer patients. The app spits out the estimated odds of laryngeal cancer, helping providers decide whether to offer the patient specialist care. 

    Or consider spasmodic dysphonia, a neurological voice disorder that triggers spasms in the muscles of the voice box, causing a strained or breathy voice. Doctors who lack experience with vocal disorders may miss the condition. This is why diagnosis takes an average of nearly 4½ years, according to a study in the Journal of Voice, and may include everything from allergy testing to psychiatric evaluation, says Powell. Artificial intelligence technology trained to recognize the disorder could help eliminate such unnecessary testing.

    Neurological and Neurodegenerative Disorders 

    (Alzheimer’s, Parkinson’s, stroke, ALS) 

    For Alzheimer’s and Parkinson’s, “one of the first changes that’s notable is voice,” usually appearing before a formal diagnosis, says Anais Rameau, MD, an assistant professor of laryngology at Weill Cornell Medical College and another member of the NIH project. Parkinson’s may soften the voice or make it sound monotone, while Alzheimer’s disease may change the content of speech, leading to an uptick in “umm’s” and a preference for pronouns over nouns.

    With Parkinson’s, vocal changes can occur decades before movement is affected. If doctors could detect the disease at this stage, before tremor emerged, they might be able to flag patients for early intervention, says Max Little, PhD, project director for the Parkinson’s Voice Initiative. “That is the ‘holy grail’ for finding an eventual cure.” 

    Again, the smartphone shows potential. In a 2022 Australian study, an AI-powered app was able to identify people with Parkinson’s based on brief voice recordings, although the sample size was small. On a larger scale, the Parkinson’s Voice Initiative collected some 17,000 samples from people across the world. “The aim was to remotely detect those with the condition using a telephone call,” says Little. It did so with about 65% accuracy. “While this is not accurate enough for clinical use, it shows the potential of the idea,” he says. 

    Rudzicz worked on the team behind Winterlight, an iPad app that analyzes 550 features of speech to detect dementia and Alzheimer’s (as well as mental illness). “We deployed it in long-term care facilities,” he says, identifying patients who need further review of their mental skills. Stroke is another area of interest, since slurred speech is a highly subjective measure, says Anderson. AI technology could provide a more objective evaluation. 

    Mood and Psychiatric Disorders 

    (Depression, schizophrenia, bipolar disorders) 

    No established biomarkers exist for diagnosing depression. Yet if you’re feeling down, there’s a good chance your friends can tell – even over the phone. 

    “We carry a lot of our mood in our voice,” says Powell. Bipolar disorder can also alter voice, making it louder and faster during manic periods, then slower and quieter during depressive bouts. The catatonic stage of schizophrenia often comes with “a very monotone, robotic voice,” says Anderson. “These are all something an algorithm can measure.” 

    Apps are already being used – often in research settings – to monitor voices during phone calls, analyzing rate, rhythm, volume, and pitch, to predict mood changes. For example, the PRIORI project at the University of Michigan is working on a smartphone app to identify mood changes in people with bipolar disorder, especially shifts that could increase suicide risk.

    The content of speech may also offer clues. In a UCLA study, published in the journal PLOS One, people with mental illnesses answered computer-programmed questions (like “How have you been over the past few days?”) over the phone. An app analyzed their word choices, paying attention to how they changed over time. The researchers found that AI analysis of mood aligned well with doctors’ assessments and that some people in the study actually felt more comfortable talking to a computer. 

    Respiratory Disorders 

    (Pneumonia, COPD)

    Beyond talking, respiratory sounds like gasping or coughing may point to specific conditions. “Emphysema cough is different, COPD cough is different,” says Bensoussan. Researchers are trying to find out if COVID-19 has a distinct cough. 

    Breathing sounds can also serve as signposts. “There are different sounds when we can’t breathe,” says Bensoussan. One is called stridor, a high-pitched wheezing often resulting from a blocked airway. “I see tons of people [with stridor] misdiagnosed for years – they’ve been told they have asthma, but they don’t,” says Bensoussan. AI analysis of these sounds could help doctors more quickly identify respiratory disorders. 

    Pediatric Voice and Speech Disorders 

    (Speech and language delays, autism)

    Babies who later have autism cry differently as early as 6 months of age, which means an app like ChatterBaby could help flag children for early intervention, says Anderson. Autism is linked to several other diagnoses, such as epilepsy and sleep disorders. So analyzing an infant’s cry could prompt pediatricians to screen for a range of conditions. 

    ChatterBaby has been “incredibly accurate” in identifying when babies are in pain, says Anderson, because pain increases muscle tension, resulting in a louder, more energetic cry. The next goal: “We’re collecting voices from babies around the world,” she says, and then tracking those children for 7 years, looking to see if early vocal signs could predict developmental disorders. Vocal samples from young children could serve a similar purpose.

    And That’s Only the Beginning 

    Eventually, AI technology may pick up disease-related voice changes that we can’t even hear. In a new Mayo Clinic study, certain vocal features detectable by AI – but not by the human ear – were linked to a three-fold increase in the likelihood of having plaque buildup in the arteries. 

    “Voice is a huge spectrum of vibrations,” explains study author Amir Lerman, MD. “We hear a very narrow range.” 

    The researchers aren’t sure why heart disease alters voice, but the autonomic nervous system may play a role, since it regulates the voice box as well as blood pressure and heart rate. Lerman says other conditions, like diseases of the nerves and gut, may similarly alter the voice. Beyond patient screening, this discovery could help doctors adjust medication doses remotely, in line with these inaudible vocal signals. 

    “Hopefully, in the next few years, this is going to come to practice,” says Lerman. 

    Still, in the face of that hope, privacy concerns remain. Voice is an identifier that’s protected by the federal Health Insurance Portability and Accountability Act, which requires privacy of personal health information. That is a major reason why no large voice databases exist yet, says Bensoussan. (This makes collecting samples from children especially challenging.) Perhaps more concerning is the potential for diagnosing disease based on voice alone. “You could use that tool on anyone, including officials like the president,” says Rameau. 

    But the primary hurdle is the ethical sourcing of data to ensure a diversity of vocal samples. For the Voice as a Biomarker project, the researchers will establish voice quotas for different races and ethnicities, ensuring algorithms can accurately analyze a range of accents. Data from people with speech impediments will also be gathered.

    Despite these challenges, researchers are optimistic. “Vocal analysis is going to be a great equalizer and improve health outcomes,” predicts Anderson. “I’m really happy that we are beginning to understand the strength of the voice.” 

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  • Researchers Identify the Role of an Alzheimer’s Disease Risk Gene in the Brain

    Researchers Identify the Role of an Alzheimer’s Disease Risk Gene in the Brain

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    UNDER EMBARGO UNTIL November 30, 2022, at 7:00 am EST

    Newswise — New York, NY (November 22, 2022) – A new study links a gene concentrated in the brain’s cleanup cells, known as microglia, to the inflammation that has increasingly emerged as a key mechanism contributing to Alzheimer’s disease. The findings may offer a new potential target for therapies for the intractable condition.

    The gene, known as inositol polyphosphate-5-phosphatase D (INPP5D), is the subject of a collaborative study conducted by researchers from the Icahn School of Medicine at Mount Sinai and the Grossman School of Medicine at NYU Langone Health that appears in the November 30 issue of Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association.

    Microglia are immune cells in the brain that act as scavengers to remove dying cells and amyloid plaques that are associated with the dementia of Alzheimer’s disease. Human genetics studies initially linked INPP5D to the risk for Alzheimer’s disease. Other studies revealed elevated levels of INPP5D in the postmortem brain tissue of Alzheimer’s disease patients, but the specific role(s) that the gene plays in both early or late disease and the mechanism contributing to these altered functions remains unknown.

    Because INPP5D in the brain is concentrated in microglia, co-senior author Michelle E. Ehrlich, M.D., Professor of Neurology, Pediatrics, and Genetics and Genomic Sciences at Icahn Mount Sinai, used mice genetically engineered to “knock down” (turn off) the mouse INPP5D gene in their microglia at the onset of pathology. This process allowed them to better see the specific impact of the missing gene on brain tissue. They then measured plaque buildup and microglial behavior approximately three months later. Since INPP5D was known to be elevated in the brains of Alzheimer’s patients, the scientists expected that the mice with that gene inactivated would be protected from the amyloid plaques that are hallmarks of Alzheimer’s disease pathology.

    “When I looked through the microscope, I was quite surprised to see that the mice lacking INPP5D in their microglia had more plaques that mice with normal microglia,” said Emilie Castranio, PhD, a postdoctoral fellow in Dr. Ehrlich’s lab and co-first author on the new paper. “Microglia frequently sit on the edges of the plaques but when INPP5D was knocked down, the plaques were completely covered with them.”

    “We are encountering unexpected results more and more with modulation of inflammation genes in Alzheimer’s,” said Dr. Ehrlich. “At this point in our understanding, we still do not know which of these genes to target for therapeutic intervention in humans, or whether to turn them up or turn them off depending on disease stage. Because these experiments are not possible in living humans, we rely on mouse models to show us the way. We also use these mice to help us predict whether a particular gene is more related to disease onset or disease progression, with the caveat that mouse and human microglia differ in important ways. Despite these differences, the plaque-associated gene signature we identified overlaps with human Alzheimer’s disease gene networks.”

    When it became clear that the INPP5D knockdown moved microglia around the brain in unexpected ways, Dr. Ehrlich recognized that detailed spatial and quantitative gene expression information was required. Spatial transcriptomics is a molecular profiling method that allows scientists to measure all the gene expression in a tissue sample and map where the expression is occurring.  Drs. Ehrlich and Castranio turned to Shane Liddelow, PhD, Assistant Professor of Neuroscience, Physiology, and Ophthalmology at NYU Langone, and co-senior author of the new study, who is a world leader in this approach. 

    The spatial transcriptomics findings emphasized the range of gene expression changes that microglia can display. Microglia near amyloid plaques are known to express genes designated as plaque-induced genes (PIGs). The INPP5D knockdown mice replicated the increases in PIGs that had been described in previous research, but the high quality of both the technical aspects and analysis of the spatial transcriptomics allowed for the identification of additional PIGs. The newly identified PIG with the greatest increase in expression in these mice was CST7, a gene encoding the protein cystatin F that is known to be impacted in Alzheimer’s and associated with prion diseases, a family of rare, progressive neurodegenerative disorders that affect both humans and animals. These findings suggest that both INPP5D and cystatin F should be considered as targets for development of novel interventions aimed at mitigating inflammation in the Alzheimer’s brain. 

    Funding for the study was provided by National Institutes of Health grants P30AG066515, U01AG046170, RF1AG058469, RF1AG059319, R01AG061894, P30AG066514, U01AG046170, RF1AG057440, U01AG046170, and RF1AG057440. Additional funding was provided by the Blas Frangione Foundation, the Neurodegenerative Diseases Consortium from MD Anderson Cancer Center, Alzheimer’s Research UK, the Gifford Family Neuroimmune Consortium as part of the Cure Alzheimer’s Fund, the Alzheimer’s Association, and NYU Langone’s Alzheimer’s Disease Resource Center. Further funding was provided by Paul Slavik.

    Liddelow maintains a financial interest in AstronauTx Ltd., a company investigating possible treatment targets for Alzheimer’s disease. The terms and conditions are being managed in accordance with the policies of NYU Langone.

    In addition to Drs. Ehrlich and Castranio, other Icahn Mount Sinai investigators in the study were Jean-Vianney Haure-Mirande, PhD; Angie Ramirez, BS; Bin Zhang, PhD; Minghui Wang, PhD, and Sam Gandy, MD, PhD.  Other study authors include study co-lead author Philip Hasel, PhD, and Rachel Kim, BA, at NYU Langone, and Charles Glabe, PhD, from the University of California, Irvine.

    About the Icahn School of Medicine at Mount Sinai
    The Icahn School of Medicine at Mount Sinai is internationally renowned for its outstanding research, educational, and clinical care programs. It is the sole academic partner for the eight member hospitals* of the Mount Sinai Health System, one of the largest academic health systems in the United States, providing care to a large and diverse patient population.  

    Ranked 14th nationwide in National Institutes of Health (NIH)  funding and among the 99th percentile in  research dollars per investigator according to the  Association of American Medical Colleges, Icahn Mount Sinai has a talented, productive, and successful faculty. More than 3,000 full-time scientists, educators and clinicians work within and across 34 academic departments and 35 multidisciplinary institutes, a structure that facilitates tremendous collaboration and synergy. Our emphasis on translational research and therapeutics is evident in such diverse areas as genomics/big data, virology, neuroscience, cardiology, geriatrics, as well as gastrointestinal and liver diseases.

    Icahn Mount Sinai offers highly competitive MD, PhD, and Master’s degree programs, with current enrollment of approximately 1,300 students. It has the largest graduate medical education program in the country, with more than 2,000 clinical residents and fellows training throughout the Health System. In addition, more than 550 postdoctoral research fellows are in training within the Health System.

    A culture of innovation and discovery permeates every Icahn Mount Sinai program. Mount Sinai’s technology transfer office, one of the largest in the country, partners with faculty and trainees to pursue optimal commercialization of intellectual property to ensure that Mount Sinai discoveries and innovations translate into healthcare products and services that benefit the public.

    Icahn Mount Sinai’s commitment to breakthrough science and clinical care is enhanced by academic affiliations that supplement and complement the School’s programs.

    Through the Mount Sinai Innovation Partners (MSIP), the Health System facilitates the real-world application and commercialization of medical breakthroughs made at Mount Sinai. Additionally, MSIP develops research partnerships with industry leaders such as Merck & Co., AstraZeneca, Novo Nordisk, and others.

    The Icahn School of Medicine at Mount Sinai is located in New York City on the border between the Upper East Side and East Harlem and classroom teaching takes place on a campus facing Central Park. Icahn Mount Sinai’s location offers many opportunities to interact with and care for diverse communities. Learning extends well beyond the borders of our physical campus, to the eight hospitals of the Mount Sinai Health System, our academic affiliates, and globally.
    ——————————————————-
    *  Mount Sinai Health System Member Hospitals: The Mount Sinai Hospital; Mount Sinai Queens; Mount Sinai Beth Israel; Mount Sinai West; Mount Sinai Morningside; Mount Sinai Brooklyn; New York Eye and Ear Infirmary of Mount Sinai; and Mount Sinai South Nassau 

    ###

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    Mount Sinai Health System

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  • Diagnostic marker found for deadly brain disease marked by dementia, movement problems

    Diagnostic marker found for deadly brain disease marked by dementia, movement problems

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    Newswise — Zooming in on a single disease and studying it intensely is often the most productive route to finding treatments. But there’s no easy way to distinguish among people living with any of the primary tauopathies — a group of rare brain diseases marked by rapidly worsening problems with thinking and movement — because the symptoms are too similar. As a result, most studies on primary tauopathies have included a mix of such diseases, even though researchers know that the diseases differ in important ways and probably require different treatments.

    Now, however, researchers at Washington University School of Medicine in St. Louis have found a biomarker that identifies, with up to 89% accuracy, people with a primary tauopathy called corticobasal degeneration (CBD). Traditional diagnostic methods for CBD are only 25% to 50% accurate, the researchers said.

    The biomarker could be developed into a tool to screen potential volunteers for CBD-specific research studies and clinical trials and, eventually, to identify people who could benefit from CBD-specific treatments, the scientists said.

    The study is published Nov. 24 in Nature Medicine.

    “Before, the only way to find out which primary tauopathy a person had was to wait until they died and then examine the person’s brain under a microscope,” said co-senior author Chihiro Sato, PhD, an assistant professor of neurology. “A patient comes in with stiffness, balance problems, slurred speech and memory issues, and it could be CBD, but it also could be progressive supranuclear palsy (PSP) or Alzheimer’s or other diseases. This biomarker can reliably identify people with CBD, which means we can use it to enroll people in clinical trials. And, down the road, it may be key to initiating therapies.”

    CBD is one of about two dozen brain diseases that are considered tauopathies because they share one critical feature: toxic tau aggregates in the brain. Individual tauopathies involve different subtypes of tau and exhibit different patterns of damage to brain cells and tissues. The collections of symptoms of the various tauopathies overlap, making it difficult for doctors to tell one from another. This complicates efforts to study them and find treatments.

    Tauopathies are classed as either primary or secondary, depending on when tau tangles appear in the course of the disease. In primary tauopathies, tau tangles form in the beginning, seemingly on their own. In secondary tauopathies, tangles form only after other changes have taken place in the brain. For example, in Alzheimer’s disease, the most common secondary tauopathy, the brain protein amyloid beta builds up for years before tau tangles appear.

    In 2020, Kanta Horie, PhD, a research associate professor of neurology and the first author on the current paper, developed a highly sensitive technique to detect specific fragments of tau in the cerebrospinal fluid that surrounds the brain and spinal cord. Horie and colleagues used the technique to identify a novel form of tau in Alzheimer’s patients, and showed that the level of the novel tau in the cerebrospinal fluid indicates the stage of the disease, and tracks with the amount of tau tangles in the brain.

    As part of this study, Horie, Sato and colleagues — including co-senior author Randall J. Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor of Neurology — used the technique to search for distinctive forms of tau linked to primary tauopathies. To ensure that the study subjects were classified accurately, Horie, Sato and Bateman collaborated with co-authors Adam Boxer, MD, PhD, Salvatore Spina, MD, PhD, and Lawren VandeVrede, MD, PhD, all in the Department of Neurology at the University of California, San Francisco. The team examined brain tissues and cerebrospinal fluid from people who had died with dementia and movement disorders, and whose specific diseases had been confirmed at autopsy. The study population included people with one of five primary tauopathies — CBD; PSP; frontotemporal lobar degeneration with microtubule association protein tau mutations (FTLD-MAPT); agyrophilic grain disease; and Pick’s disease — as well as Alzheimer’s, and dementia not related to tau. For comparison, they also examined samples from people without dementia.

    Two particular forms of tau — microtubule binding region (MTBR)-tau 275 and MTBR-tau 282 — were unusually high in the brains and low in the cerebrospinal fluid of patients with CBD and a subset of FTLD-MAPT. Further investigation showed that these forms of tau distinguish people with CBD from those with other primary tauopathies with 84% to 89% accuracy, depending on the disease.

    “Even if there’s an experimental drug available that specifically targets the kind of tau in CBD, it is very challenging to test it without a biomarker,” Horie said. “The trial might fail even when the drug works if the population is heterogenous. Drug trials that specifically target the kind of tau in CBD can be improved by enrolling correctly diagnosed patients. Having a biomarker opens up a pathway for pharmaceutical companies to improve clinical trials and accelerate research toward therapies for CBD.”

    Several experimental drugs targeting tau are in the pipeline. Most were designed with Alzheimer’s patients in mind, but they may be effective as therapies for primary tauopathies. Horie’s technique could be used to find biomarkers for other primary tauopathies, opening the door to more clinical trials, the researchers said.

    “CBD patients and families are desperate for effective therapies, but it has been challenging to organize clinical trials for this fatal disease,” Boxer said. “Until now, we did not have a specific biomarker to accurately diagnose patients. This new biomarker also opens the door to testing many new tau-directed therapies for CBD, because it may allow us to directly measure the ability of these treatments to lower toxic tau protein levels in patients’ brains.”

     

    Horie K, Barthélemy NR, Spina S, VandeVrede L, He Y, Paterson RW, Wright BA, Day GS, Davis AA, Karch CM, Seeley WW, Perrin RJ, Koppisetti RK, Shaikh F, Lario Lago A, Heuer HW, Ghoshal N, Gabelle A, Miller BL, Boxer AL, Bateman RJ, Sato C. CSF tau microtubule binding region identifies pathological changes in primary tauopathies. Nature Medicine. Nov. 24, 2022. DOI: 10.1038/s41591-022-02075-9

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    Washington University in St. Louis

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  • Why Do Women Get Alzheimer’s More Than Men? Study Offers Clue

    Why Do Women Get Alzheimer’s More Than Men? Study Offers Clue

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    Nov. 10, 2022 — Of the more than 6 million Alzheimer’s patients in the U.S. age 65 or older, nearly two-thirds are women. A new study may help explain the gender gap — and offer clues to new treatments for helping patients of both sexes fight back. 

    Scientists at Case Western Reserve University zeroed in on a gene named USP11, found on the X chromosome. People assigned female at birth have two X chromosomes, while people assigned male at birth have one X and one Y. So while all males have one copy of USP11, females have two.

    Your Body’s Trash Collection System

    To understand the role of USP11 in the body, imagine you’re on the sidewalk of a bustling city. Just like the residents in the buildings, our brains create waste that must be hauled away. If the waste was left on the sidewalks without removal, it would pile up, seep into roadways, disrupt life, and become toxic to the environment. 

    In the brain, one waste product is a protein called tau. Too little tau can damage nerve cells, explain researchers David Kang, PhD, and JungA “Alexa” Woo, PhD, who led the study. But too much becomes toxic and can lead to neurodegenerative diseases such as Alzheimer’s. (In fact, new research suggests that testing for changes in tau may someday help doctors diagnose Alzheimer’s earlier.) 

    To manage tau, your brain uses a regulatory protein called ubiquitin to “tag” or signal the body that extra tau should be removed. In the city analogy, ubiquitin is like attaching a sign to a garbage bag, telling waste management to haul the bag away.

    USP11’s job is to give instructions to make an enzyme that removes the ubiquitin tag to maintain balance. (You don’t want to get rid of all tau protein. Justsomeof it.) But if too much of the enzyme is present, too much tau gets untagged — and not enough of it gets cleared. 

    “Our study showed USP11 is higher in females than males in both humans and in mice,” Kang says. “That’s already true before the onset of dementia. But once someone has Alzheimer’s disease, USP11 is much higher — regardless of sex.” 

    The study adds to a growing body of evidence that shows women may be more vulnerable than men to higher levels of tau, possibly explaining why women are affected by the disease more often than men. 

    But what if there was a way to “turn off” or deactivate the USP11 gene? Might that help prevent Alzheimer’s? And could it be done safely?  

    What Happened When the Gene Was Eliminated?

    To examine these questions, researchers used a method of gene manipulation to completely delete the USP11 gene in mice. They then examined the mice for changes. The result? The mice seemed fine. 

    “The mice bred well. Their brains looked fine,” Woo says.  

    It would not be possible — or ethical — to remove a gene from humans. But when a medical condition makes a certain gene unhelpful, that gene can be partially blocked or expression of the gene can be reduced with medication. In fact, medications targeting enzymes are common. Examples include statins for cardiovascular disease or HIV treatments that inhibit protease enzymes.

    “If we are able to identify some type of medicine that would inhibit USP11, our study suggests it would be well tolerated and benefit women,” Woo says. 

    Kang also cautions that the process for creating such a therapy takes at least 10 to 15 years. The researchers say they’d like to shorten the timeline and plan to study currently approved FDA medications to see if any might work to target USP11 gene activity — and hopefully bring forth a new treatment for Alzheimer’s sooner. 

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  • Covid-19 activates same inflammation in the brain as Parkinson’s disease, finds study

    Covid-19 activates same inflammation in the brain as Parkinson’s disease, finds study

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    There is a potential future risk of neurodegenerative conditions in people who have had Covid, according to a study conducted by scientists from the University of Queensland. The scientists involved in the research have said that Covid infection activates the same inflammatory response in the brain as Parkinson’s disease.

    The research is published in Nature’s Molecular Psychiatry. Professor Trent Woodruff who led the research said: “We studied the effect of the virus on the brain’s immune cells, ‘microglia’ which are the key cells involved in the progression of brain diseases like Parkinson’s and Alzheimer’s.”  

    “Our team grew human microglia in the laboratory and infected the cells with SARS-CoV-2, the virus that causes Covid-19. We found the cells effectively became ‘angry’, activating the same pathway that Parkinson’s and Alzheimer’s proteins can activate in disease, the inflammasomes,” said Woodruff.

    The scientists said that triggering the inflammasome pathway sparked a ‘fire’ in the brain, which begins a chronic and sustained process of killing off neurons. “It’s kind of a silent killer because you don’t see any outward symptoms for many years,” said Dr Albornoz Balmaceda, another scientist from the University of Queensland.

    “It may explain why some people who’ve had Covid are more vulnerable to developing neurological symptoms similar to Parkinson’s disease,” Balmaceda said. 

    The researchers found the spike protein of the virus was enough to start the process and was further exacerbated when there were already proteins in the brain linked to Parkinson’s.

    “So if someone is already pre-disposed to Parkinson’s, having Covid-19 could be like pouring more fuel on that ‘fire’ in the brain,” Professor Woodruff said, adding that the same would apply for a predisposition for Alzheimer’s and other dementias that have been linked to inflammasomes.

    But the study also found a potential treatment. The researchers administered a class of inhibitory drugs developed at the university which are currently in clinical trials with Parkinson’s patients. 

    “We found it successfully blocked the inflammatory pathway activated by Covid-19, essentially putting out the fire,” Dr Albornoz Balmaceda said. He further said that the drug reduced inflammation in both Covid-19-infected mice and the microglia cells from humans, suggesting a possible treatment approach to prevent neurodegeneration in the future.

    Scientists said while the similarity between how Covid-19 and dementia diseases affect the brain was concerning, it also meant a possible treatment was already in existence. “Further research is needed, but this is potentially a new approach to treating a virus that could otherwise have untold long-term health ramifications,” said Woodruff.
     

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  • Halloween Can Be a Scary Time for People With Dementia. Here’s How to Help

    Halloween Can Be a Scary Time for People With Dementia. Here’s How to Help

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    By Cara Murez 

    HealthDay Reporter

    THURSDAY, Oct. 27, 2022 (HealthDay News) — When there are suddenly creepy decorations and lots of knocks at the door from strangers, Halloween can be frightening for someone living with dementia.

    It is possible to keep a loved one living with the disease calm and safe, while also including that family member in celebrating the holiday quietly, experts say.

    “Like with many other traditions, there are adaptations families can make to help their relatives living with dementia have a safe and enjoyable Halloween,” said Jennifer Reeder, director of educational and social services for the Alzheimer’s Foundation of America.

    “We encourage caregivers to follow a few quick and easy steps to keep the ‘Happy’ in ‘Happy Halloween’ on Oct. 31,” Reeder said in a foundation news release.

    The foundation’s experts suggest adapting the celebration by reminiscing about past Halloween costumes or activities while looking at old family pictures. Watch a non-threatening program about Halloween.

    Give your loved one healthy snacks, such as fruit. Too much candy can increase agitation.

    For some, it may be possible to have a loved one with dementia help hand out candy to trick-or-treaters, but never leave the person alone to do so, which could be frightening, confusing and a safety risk, the foundation suggests.

    Try playing calming music, engaging in a quiet activity such as reading a book together or providing soothing reassurance.

    Minimize distress by avoiding potentially scary decorations, such as fake skeletons, cobwebs, witches and monsters. It’s especially important to avoid exposure to interactive decorations that talk or scream when someone passes by or that have flashing or flickering lights. These can scare and cause someone with dementia to wander away, even from their own home.

    Stay safe with the lights on inside and outside the home, so burglars and vandals don’t think the house is empty, the foundation suggests. Another option for candy is to leave a bowl outside the door with a sign that says, “Please take one.”

    The AFA Helpline at 866-232-8484 or via the website www.alzfdn.org offers an opportunity to speak with a licensed social worker seven days a week.

    More information

    The U.S. Centers for Disease Control and Prevention has more on dementia.

     

    SOURCE: Alzheimer’s Foundation of America, news release, Oct. 24, 2022

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  • The latest news in Opioids, Drug Abuse, and Addiction

    The latest news in Opioids, Drug Abuse, and Addiction

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    Overdose deaths remain a leading cause of injury-related death in the United States. The majority of overdose deaths involve opioids. Here are some of the latest articles that have been added to the Drugs and drug abuse channel on Newswise, a free source for journalists. For the latest in addiction research, see the Addiction channel.

    Outpatient Visits Are Critical to Success of Treating Opioid-Use Disorder, Researchers Find (embargoed until 26-Oct-2022 12:05 AM EDT)

    Opioid prescribing after surgery remains the same for seniors, but doses are lower, study shows

    Opioid abuse decreases during pandemic, yet higher rates persist for sexual minorities

    Home sensors can detect opioid withdrawal signs at night

    Human Cocaine and Heroin Addiction Is Found Tied to Impairments in Specific Brain Circuit Initially Implicated in Animals

    Researchers seek to unravel the mystery of susceptibility to drug addiction

    New study reveals undercount of Cook County opioid deaths

    Artificial intelligence tools quickly detect signs of injection drug use in patients’ health records

    American adolescent substance abuse has declined — with the exception of cannabis and vaping

    Opioid addiction treatment disparities could worsen if phone telehealth option ends, study suggests

     

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  • American Neurological Association Announces New Leadership

    American Neurological Association Announces New Leadership

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    Newswise — [MOUNT LAUREL, NJ, October 24, 2022] — The American Neurological Association (ANA), the professional organization representing the world’s leading academic neurologists and neuroscientists, has appointed Brenda Orffer, CAE, as its new Chief Executive Officer and Nadine Goldberg, PhD, MS, as Chief Program Officer.

    “We are delighted to welcome Brenda to the ANA and Nadine to a newly created role in the ANA,” said Frances E. Jensen, MD, FANA, FACP, president of the ANA and chair of the neurology department at the University of Pennsylvania. “The appointments of these accomplished professionals position our organization for continuity and strength as we look to the future.”

    Orffer will be responsible for overall operations of the ANA, including governance, budgeting, and financial oversight. She comes to the ANA from the Washington Health Care Association, where she served as executive vice president of the statewide nonprofit organization representing more than 500 assisted living and skilled nursing facilities.

    A graduate of Kent Christian College with a bachelor’s degree in theology, Orffer also served as mayor of the City of McCleary, Washington, and as a member of its city council. She currently volunteers as a member of the quality improvement committee at Summit Pacific Medical Center, giving her a perspective on the work that community hospitals do to improve the patient experience.

    “I’m excited to be part of an organization with a rich history and to help ensure its bright future,” Orffer said. “When I think about the discoveries being generated in neurology today, it’s just fascinating. I now have a front row seat to some of the most innovative technologies and advances in medicine.”

    Changing Hats

    Formerly executive director of the ANA, Goldberg will now set her focus on delivering the outstanding programming — both at the Annual Meeting and throughout the year — for which the ANA is known. As Chief Program Officer, she will play a key role in the development, strategy, and management of the organization as it supports academic neurologists and neuroscientists nationwide. She will oversee organizational partnerships and initiatives as well as all programming, including the ANA’s prestigious Annual Meeting. Building on her established work in professional education, she will continue to develop and manage membership programming that hones career skills and keeps members up-to-date on current issues, from online education and CME to the Research Careers Reimagined course for early-career professionals.

    Prior to joining the ANA in 2016, Goldberg held executive positions with the Juvenile Products Manufacturers Association and First Candle, a maternal and child welfare nonprofit. A graduate of the University of Greenwich with a bachelor’s degree in sociology, Goldberg earned a master’s degree in criminology from the University of Maryland Eastern Shore and a doctorate in medical sociology from Howard University.

    During her tenure as executive director, Goldberg stewarded the ANA’s continued growth, collaborating with industry leaders and cross-functional teams to develop innovative services and research that advanced the field of neurology. She expanded educational opportunities, cultivated participation of early-career academic neurologists, and implemented new awards programs to recognize and advance the work of ANA members from backgrounds that are under-represented in medicine.

    “It’s the ANA’s priority to ensure that our members have programming that supports them throughout their careers,” Goldberg said. “The ANA is driving a future of constant improvement and innovation across the fields of neurology and neuroscience. We must ensure that ANA members — including those who are in leadership positions, those just starting out, and those who are traditionally underrepresented — have the resources, support, and networks they need to make an impact.”

     

    About the American Neurological Association (ANA)

    From advances in stroke and dementia to movement disorders and epilepsy, the American Neurological Association has been the vanguard of research since 1875 as the premier professional society of academic neurologists and neuroscientists devoted to understanding and treating diseases of the nervous system. Its monthly Annals of Neurology is among the world’s most prestigious medical journals, and the ANA’s Annals of Clinical and Translational Neurology is an online-only, open access journal providing rapid dissemination of high-quality, peer-reviewed research related to all areas of neurology. The acclaimed ANA Annual Meeting draws faculty and trainees from the top academic departments across the U.S. and abroad for groundbreaking research, networking, and career development. For more information, visit www.myana.org or @TheNewANA1 on Twitter.

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  • Detecting Alzheimer’s disease in the blood

    Detecting Alzheimer’s disease in the blood

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    Newswise — Researchers from Hokkaido University and Toppan have developed a method to detect build-up of amyloid β in the brain, a characteristic of Alzheimer’s disease, from biomarkers in blood samples.

    Alzheimer’s disease is a neurodegenerative disease, characterised by a gradual loss of neurons and synapses in the brain. One of the primary causes of Alzheimer’s disease is the accumulation of amyloid β (Aβ) in the brain, where it forms plaques. Alzheimer’s disease is mostly seen in individuals over 65 years of age, and cannot currently be stopped or reversed. Thus, Alzheimer’s disease is a major concern for nations with ageing populations, such as Japan.

    A team of scientists from Hokkaido University and Toppan, led by Specially Appointed Associate Professor Kohei Yuyama at the Faculty of Advanced Life Science, Hokkaido University, have developed a biosensing technology that can detect Aβ-binding exosomes in the blood of mice, which increase as Aβ accumulates in the brain. Their research was published in the journal Alzheimer’s Research & Therapy.

    When tested on mice models, the Aβ-binding exosome Digital ICATM (idICA) showed that the concentration of Aβ-binding exosomes increased with the increase in age of the mice. This is significant as the mice used were Alzheimer’s disease model mice, where Aβ builds up in the brain with age.

    In addition to the lack of effective treatments of Alzheimer’s, there are few methods to diagnose Alzheimer’s. Alzheimer’s can only be definitively diagnosed by direct examination of the brain—which can only be done after death. Aβ accumulation in the brain can be measured by cerebrospinal fluid testing or by positron emission tomography; however, the former is an extremely invasive test that cannot be repeated, and the latter is quite expensive. Thus, there is a need for a diagnostic test that is economical, accurate and widely available.

    Previous work by Yuyama’s group has shown that Aβ build-up in the brain is associated with Aβ-binding exosomes secreted from neurons, which degrade and transport Aβ to the microglial cells of the brain. Exosomes are membrane-enclosed sacs secreted by cells that possess cell markers on their surface. The team adapted Toppan’s proprietary Digital Invasive Cleavage Assay (Digital ICATM) to quantify the concentration of Aβ-binding exosomes in as little as 100 µL of blood. The device they developed traps molecules and particles in a sample one-by-one in a million micrometer-sized microscopic wells on a measurement chip and detects the presence or absence of fluorescent signals emitted by the cleaving of the Aβ-binding exosomes.

    Clinical trials of the technology are currently underway in humans. This highly sensitive idICA technology is the first application of ICA that enables highly sensitive detection of exosomes that retain specific surface molecules from a small amount of blood without the need to learn special techniques; as it is applicable to exosome biomarkers in general, it can also be adapted for use in the diagnosis of other diseases.

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    Hokkaido University

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