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Aluminum and Alzheimer’s disease: after a century of …

Posted: August 2, 2021 at 1:54 am


The brain is a highly compartmentalized organ exceptionally susceptible to accumulation of metabolic errors. Alzheimer's disease (AD) is the most prevalent neurodegenerative disease of the elderly and is characterized by regional specificity of neural aberrations associated with higher cognitive functions. Aluminum (Al) is the most abundant neurotoxic metal on earth, widely bioavailable to humans and repeatedly shown to accumulate in AD-susceptible neuronal foci. In spite of this, the role of Al in AD has been heavily disputed based on the following claims: 1) bioavailable Al cannot enter the brain in sufficient amounts to cause damage, 2) excess Al is efficiently excreted from the body, and 3) Al accumulation in neurons is a consequence rather than a cause of neuronal loss. Research, however, reveals that: 1) very small amounts of Al are needed to produce neurotoxicity and this criterion is satisfied through dietary Al intake, 2) Al sequesters different transport mechanisms to actively traverse brain barriers, 3) incremental acquisition of small amounts of Al over a lifetime favors its selective accumulation in brain tissues, and 4) since 1911, experimental evidence has repeatedly demonstrated that chronic Al intoxication reproduces neuropathological hallmarks of AD. Misconceptions about Al bioavailability may have misled scientists regarding the significance of Al in the pathogenesis of AD. The hypothesis that Al significantly contributes to AD is built upon very solid experimental evidence and should not be dismissed. Immediate steps should be taken to lessen human exposure to Al, which may be the single most aggravating and avoidable factor related to AD.

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New research links COVID-19 and signs of Alzheimer’s disease – Medical News Today

Posted: at 1:54 am


Scientists presenting research at the AAIC 2021, held online and in Denver, CO, have found links between COVID-19 and longer-term cognitive issues, including biological signs of Alzheimers disease.

The findings lay the ground for larger longitudinal studies to explore in more detail the neurological effects of COVID-19.

COVID-19 is primarily a respiratory condition. The Centers for Disease Control and Prevention (CDC) note that COVID-19 symptoms can include mild respiratory problems, more severe low oxygen levels and shortness of breath, and life threatening issues affecting multiple organs across a persons body.

Much research has been done to understand these acute symptoms, and there are now many different treatment options open to clinicians.

However, the effects of COVID-19 do not always end after the acute phase of the condition.

As the pandemic progressed, anecdotal evidence suggested many people who had recovered from COVID-19 were still experiencing a variety of symptoms. This became known as long COVID.

According to Dr. A. V. Raveendran, of the Government Medical College in Manjeri, India, and his colleagues, symptoms of long COVID can include profound fatigue, breathlessness, cough, chest pain, palpitations, headache, joint pain, myalgia and weakness, insomnia, pins and needles, diarrhea, rash or hair loss, impaired balance and gait, neurocognitive issues, including memory and concentration problems, and worsened quality of life.

At the AAIC 2021, researchers presented a number of studies that focus on the neurological issues associated with the longer-term effects of COVID-19.

According to Dr. Heather M. Snyder, Alzheimers Association vice president of medical and scientific relations, [t]hese new data point to disturbing trends showing COVID-19 infections leading to lasting cognitive impairment and even Alzheimers symptoms.

With more than 190 million cases and nearly 4 million deaths worldwide, COVID-19 has devastated the entire world. It is imperative that we continue to study what this virus is doing to our bodies and brains. The Alzheimers Association and its partners are leading, but more research is needed, she said.

In one study, Dr. Gabriel De Erausquin, of the University of Texas Health Science Center at San Antonio Long School of Medicine, as well as colleagues from the Alzheimers Association leading a consortium on links between COVID-19 and the nervous system, looked at neurological issues in Amerindians from Argentina who had recovered from acute COVID-19.

The 300 participants were assessed 36 months after having COVID-19. The researchers found that more than 50% of the participants had issues with forgetfulness and that around 25% also experienced executive dysfunction and language issues.

The researchers noted an association between these cognitive issues and loss of smell but not with the severity of the initial SARS-CoV-2 infection.

According to Dr. Erausquin, [we are] starting to see clear connections between COVID-19 and problems with cognition months after infection.

[It is] imperative we continue to study this population, and others around the world, for a longer period of time to further understand the long-term neurological impacts of COVID-19.

In another study presented at the conference, Prof. Thomas M. Wisniewski, professor of neurology, pathology, and psychiatry at New York University Grossman School of Medicine, and his colleagues explored the possible links between COVID-19 and clinical signs of Alzheimers disease.

The researchers took blood plasma samples from 310 people who had been admitted to hospital with COVID-19. Of those, 158 had neurological symptoms associated with COVID-19 most frequently, confusion while 152 did not.

In the patients who did not have cognitive issues prior to developing COVID-19 but then did develop neurological symptoms, the researchers found an increase in biological markers associated with Alzheimers disease, brain injury, and neuroinflammation, compared with the patients who did not have neurological symptoms.

These included total tau, neurofilament light, glial fibrillary acid protein, phosphorylated tau, and ubiquitin carboxyl-terminal hydrolase L1. The researchers also noted a correlation between some of these markers and C-reactive peptide.

Prof. Wisniewski explains: These findings suggest that patients who had COVID-19 may have an acceleration of Alzheimers-related symptoms and pathology. However, more longitudinal research is needed to study how these biomarkers impact cognition in individuals who had COVID-19 in the long term.

Researchers also presented findings looking at the relationship between cognitive issues linked to COVID-19, and peoples physical condition and blood oxygen levels.

Dr. George D. Vavougios, a postdoctoral researcher for the University of Thessaly in Greece, and his colleagues recruited 32 people who had been hospitalized with mild or moderate COVID-19 and then discharged 2 months later.

Just over half of the participants had issues with cognitive decline, including short-term memory impairment as well as multidomain impairment without short-term memory issues.

The researchers found a correlation between worse levels of cognitive scores and being older, having a larger waist circumference, and a higher waist-to-hip ratio.

The participants also took a 6-minute walking test. After accounting for sex and age, the researchers found a link between worse memory and thinking scores and lower blood oxygen levels.

Dr. Vavougios says: A brain deprived of oxygen is not healthy, and persistent deprivation may very well contribute to cognitive difficulties. These data suggest some common biological mechanisms between COVID-19s dyscognitive spectrum and post-COVID-19 fatigue that have been anecdotally reported over the last several months.

The research presented at the conference is also supported by a new study published in The Lancet, which drew on data from over 80,000 participants. Having accounted for a range of factors, the researchers behind this study found that people who had recovered from COVID-19 had significant cognitive issues, compared with a control group.

Speaking to Medical News Today, Dr. Adam Hampshire, of the Department of Brain Sciences, Dementia Research Institute, Care Research and Technology Centre, Imperial College London in the United Kingdom, and the corresponding author of the study, said the study emerged out of ongoing research he was conducting when the pandemic took hold.

By coincidence, when the pandemic accelerated in the U.K., I was in the process of collecting one of the largest online surveys of cognitive abilities to have been conducted.

He went on to say: Several peers wrote to me noting that the study could be extended to address questions about the potential impact of the virus, and of the pandemic more broadly, on cognition and mental health. I had been thinking along similar lines so decided to try and help address this important question.

Dr. Hampshire said that the findings make clear a link between cognitive dysfunction and COVID-19 but that more research needs to be done to confirm these findings, explore them in more detail, and understand what, if any, causal mechanisms may be underlying them.

We have identified a worrying association between [COVID-19] illness and cognitive deficits. We also have ruled out many potentially confounding factors.

What is needed is a combination of longitudinal studies that determine how long these deficits last and to disentangle causality, as well as brain imaging studies to understand the underlying neural basis. Such work is underway, and some of those studies are using our assessment software, which I have made available for this purpose.

Dr. Adam Hampshire

For live updates on the latest developments regarding the novel coronavirus and COVID-19, click here.

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New research links COVID-19 and signs of Alzheimer's disease - Medical News Today

Memory Effects Of Long COVID-19 Can Resemble Alzheimer’s : Shots – Health News – NPR

Posted: at 1:54 am


Medical staff members check on a patient in the COVID-19 Intensive Care Unit at United Memorial Medical Center in Houston last November. Doctors are now investigating whether people with lingering cognitive symptoms may be at risk for dementia. Go Nakamura/Bloomberg via Getty Images hide caption

Medical staff members check on a patient in the COVID-19 Intensive Care Unit at United Memorial Medical Center in Houston last November. Doctors are now investigating whether people with lingering cognitive symptoms may be at risk for dementia.

Before she got COVID-19, Cassandra Hernandez, 38, was in great shape both physically and mentally.

"I'm a nurse," she says. "I work with surgeons and my memory was sharp."

Then, in June 2020, COVID-19 struck Hernandez and several others in her unit at a large hospital in San Antonio.

"I went home after working a 12-hour shift and sat down to eat a pint of ice cream with my husband and I couldn't taste it," she says.

The loss of taste and smell can be an early sign that COVID-19 is affecting a brain area that helps us sense odors.

Hernandez would go on to spend two weeks in the hospital and months at home disabled by symptoms including tremors, extreme fatigue and problems with memory and thinking.

"I would literally fall asleep if I was having a conversation or doing anything that involved my brain," she says.

Now, researchers at UT Health San Antonio are studying patients like Hernandez, trying to understand why their cognitive problems persist and whether their brains have been changed in ways that elevate the risk of developing Alzheimer's disease.

The San Antonio researchers are among the teams of scientists from around the world who will present their findings on how COVID-19 affects the brain at the Alzheimer's Association International Conference, which begins Monday in Denver.

What scientists have found so far is concerning.

For example, PET scans taken before and after a person develops COVID-19 suggest that the infection can cause changes that overlap those seen in Alzheimer's. And genetic studies are finding that some of the same genes that increase a person's risk for getting severe COVID-19 also increase the risk of developing Alzheimer's.

Alzheimer's diagnoses also appear to be more common in patients in their 60s and 70s who have had severe COVID-19, says Dr. Gabriel de Erausquin, a professor of neurology at UT Health San Antonio. "It's downright scary," he says.

And de Erausquin and his colleagues have noticed that mental problems seem to be more common in COVID-19 patients who lose their sense of smell, perhaps because the disease has affected a brain area called the olfactory bulb.

"Persistent lack of smell, it's associated with brain changes not just in the olfactory bulb but those places that are connected one way or another to the smell sense," he says.

Those places include areas involved in memory, thinking, planning and mood.

COVID-19's effects on the brain also seem to vary with age, de Erausquin says. People in their 30s seem more likely to develop anxiety and depression.

"In older people, people over 60, the foremost manifestation is forgetfulness," he says. "These folks tend to forget where they placed things, they tend to forget names, they tend to forget phone numbers. They also have trouble with language; they begin forgetting words."

The symptoms are similar to those of early Alzheimer's, and doctors sometimes describe these patients as having an Alzheimer's-like syndrome that can persist for many months.

"Those people look really bad right now," de Erausquin says. "And the expectation is that it may behave as Alzheimer's behaves, in a progressive fashion. But the true answer is we don't know."

Another scientist who will present research at the Alzheimer's conference is Dr. Sudha Seshadri, founding director of the Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases at UT Health San Antonio.

The possibility that COVID-19 might increase the risk of Alzheimer's is alarming, Seshadri says. "Even if the effect is small, it's something we're going to have to factor in because the population is quite large," she says.

In the U.S. alone, millions of people have developed persistent cognitive or mood problems after getting COVID-19. It may take a decade to know whether these people are more likely than uninfected people to develop Alzheimer's in their 60s and 70s, Seshadri says.

Studies of people who have had COVID-19 may help scientists understand the role infections play in Alzheimer's and other brain diseases. Previous research has suggested that exposure to certain viruses, including herpes, can trigger an immune response in the brain that may set the stage for Alzheimer's.

"If one understands how the immune response to this virus is accelerating [Alzheimer's] disease, we may learn about the impact of other viruses," Seshadri says.

Meanwhile, people like Cassandra Hernandez, the nurse, are simply trying to get better. More than a year after getting sick, she says, her brain is still foggy.

"We were at dinner and I forgot how to use a fork," she says. "It was embarrassing."

Even so, Hernandez says she's improving slowly.

"Before this I was working on my master's," she says. "Now I can do basic math, addition and subtraction, I can read at a fifth-grade level. I'm still working hard every day."

Hernandez has been working with Dr. Monica Verduzco-Gutierrez, chair of the department of physical medicine and rehabilitation at UT Health and director of the COVID-19 recovery clinic.

Verduzco-Gutierrez says her practice used to revolve around people recovering from strokes and traumatic brain injuries. Now she spends some days seeing only patients recovering from COVID-19.

The most common complaint is fatigue, Verduzco-Gutierrez says. But these patients also frequently experience migraine headaches, forgetfulness, dizziness and balance issues, she says.

Some of these patients may never recover fully, Verduzco-Gutierrez says. But she's hopeful for Hernandez.

"She's made so much improvement and I would love for her to go back to nursing," Verduzco-Gutierrez says. "But again, we don't know what happens with this disease."

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Memory Effects Of Long COVID-19 Can Resemble Alzheimer's : Shots - Health News - NPR

New genetically modified mouse model mimics multiple aspects of human Alzheimer’s disease – National Institute on Aging

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NIA-supported scientists have developed a new mouse model that produces a form of the human beta-amyloid protein, a hallmark of Alzheimers disease. An important research tool, mouse models enable the exploration of genetic, environmental, and behavioral aspects of Alzheimers, as well as make it possible to test drug candidates before human studies. The new mouse model, which was reported in a recent article in Nature Communications, can be used by other scientists to advance Alzheimers research.

Many factors, including gene changes, the aging process, and conditions in the environment, can promote the gradual development of Alzheimers. NIA invests in research to explore various disease-causing mechanisms and identify drug candidates that might prevent or delay the onset of Alzheimers.

As part of these investments, NIA established the Model Organism Development and Evaluation for Late-Onset Alzheimers Disease (MODEL-AD) consortium to develop new animal models of late-onset Alzheimers, to characterize the models relative to multiple aspects of human disease, and to make all data and models available to researchers in academia and the biotechnology and pharmaceutical industries via the NIA-supported AD Knowledge Portal. To date, the MODEL-AD teams have generated more than 50 new mouse models.

An international team led by researchers at the University of California, Irvine, one of five MODEL-AD consortium institutions, set out to engineer a mouse model that could mimic the molecular pathways that lead to the late-onset, most common form of Alzheimers. This form does not have symptoms before about age 60 and occurs sporadically, rather than in several members of a family.

Most mouse models already being used to study Alzheimers were made to overexpress amyloid precursor protein. But these models are imperfect because the mice overproduce beta-amyloid in addition to other protein fragments.

The University of California, Irvine, research team had a different approach. The team slightly modified a mouse gene so that the mice could develop the human version of beta-amyloid protein. Then the team used the gene knock-in method to insert the modified gene at a specific location. The knock-in method helps scientists study the development of a disease and its effects on the body.

Next, the team analyzed the brains of the genetically modified mice and confirmed the presence of the human beta-amyloid. The protein was produced at normal levels, rather than overproduced, as in most other mouse models.

The team noted that the mice developed behavior changes and cognitive impairment as they grew old, like what occurs in many people with beta-amyloid plaques in their brain. The mice also had changes in gene expression that resembled patterns detected in the brains of people with Alzheimers. When the team blocked the modified gene so that the mice could not develop beta-amyloid, the mice did not develop age-related cognitive impairment.

This new mouse model with human beta-amyloid provides a novel way for researchers to study the aging, genetic, and environmental factors that promote Alzheimers. It can be used to introduce other Alzheimers risk and protective genetics factors and explore how genes and the environment are involved in the disease. In addition, researchers can use this mouse model to test the effectiveness of therapeutic agents.

The project was funded in part by NIA grants R01AG027544, P01AG000538, R21AG054884, U54AG054349, R01AG049562, R01AG056768, and P50AG016573.

These activities relate to NIHs AD+ADRD Research Implementation Milestone 4.A, Support the development of the next generation of animal models based on the current understanding of genetic and environmental risk and protective factors for AD and related dementias, using genome editing and other cutting edge technologies (optogenetics/deep brain stimulation/trans-magnetic stimulation, and next generation in vivo imaging) to facilitate assessment and validation of findings from human studies and Milestone 4.B, Create infrastructure/resources for extensive characterization of existing and new animal models and development of standardized and rigorous methods for preclinical efficacy testing including web-based resources for transparent reporting of both positive and negative findings.

Reference: Baglietto-Vargas D, et al. Generation of a humanized A expressing mouse demonstrating aspects of Alzheimers disease-like pathology. Nature Communications. 2021;12(1):2421. doi: 10.1038/s41467-021-22624-z.

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New genetically modified mouse model mimics multiple aspects of human Alzheimer's disease - National Institute on Aging

Biogen and Ionis post ‘encouraging’ early results for Alzheimer’s disease candidate – PMLiVE

Posted: at 1:54 am


Biogen and Ionis have revealed topline data from an early-stage study evaluating its investigational Alzheimers disease drug candidate BIIB080 (IONIS-MAPT Rx).

The phase 1b study of BIIB080 met its primary objective, demonstrating an encouraging safety and tolerability profile in patients with mild Alzheimers disease.

In this study, investigators also noted that BIIB080 demonstrated both robust time- and dose-dependent lowering of tau protein in cerebrospinal fluid (CSF) over the three-month treatment period, with sustained reductions also observed in the six-month post-treatment period.

For BIIB080-treated patients, there were dose-dependent decreases in the concentration of total-tau in CSF eight weeks after their last dose. The mean percentage reduction was 30%, 40% and 49% in the low-, medium- and high-dose groups treated every four weeks respectively.

For patients in the group treated every 12 weeks, BIIB080 treatment led to a 42% reduction in the concentration of total-tau in CSF.

After 16 weeks post-dose, total tau in CSF also continued to decline in BIIB080-treated patients in both the high-dose four-week and 12-week groups, with a 55% and 49% reduction from baseline respectively.

"We are encouraged by the topline results from this study of BIIB080, which demonstrate the potential of Ionis' antisense technology to successfully target what we believe is a root cause of Alzheimer's disease," said C Frank Bennett, chief scientific officer and franchise leader for neurological programmes at Ionis.

"These study results support further investigation of BIIB080 for the treatment of Alzheimer's disease and suggest that antisense-mediated suppression of tau protein may be a feasible therapeutic approach for other tauopathies, he added.

"Biogen is encouraged by the results of this trial, and we look forward to our continued research in future clinical studies with this promising investigational asset, said Alfred Sandrock, head of research and development at Biogen.

In June, Biogens aducanumab was approved with the brand name Aduhelm for the treatment of Alzheimers disease, in a landmark moment for the therapy area.

The approval did not go without criticism, however, with The Institute for Clinical and Economic Review (ICER) among others maintaining that the evidence on aducanumab is insufficient to be able to demonstrate that patients get benefits that would outweigh the risks and harms of this treatment.

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Biogen and Ionis post 'encouraging' early results for Alzheimer's disease candidate - PMLiVE

Benway will chair the 2021 North Central Ohio Walk to End Alzheimer’s – Richland Source

Posted: at 1:54 am


MANSFIELD Cheryl Benway will lead the communitys efforts to raise money to support Alzheimers care, support and research as the Chair of the 2021 North Central Ohio Walk to End Alzheimers.

The North Central Ohio Walk is Saturday, Sept. 11, and participants this year will be able to physically join forces to recreate the driving movement and energy that fuels the fight to end Alzheimers.

The Walk will take place in-person at OSU/NCSC Campus in Mansfield. The Promise Garden and Display Area open at 9 a.m. and the Walk Ceremony begins at 10 a.m. Participants will walk on a paved path around campus at the close of the ceremony.

Julia Pechlivanos, Executive Director of the Alzheimers Association Northwest Ohio Chapter, said the Chapter is excited to move back to an in-person Walk experience this year because it offers the opportunity for people who have been impacted by dementia including caregivers, family, friends, and colleagues, to share their stories with one another.

The health and safety of participants, staff and volunteers remain the Chapters top priority. In addition to the OSU Campus location, we will also continue to offer options to participate online and in your neighborhood, Pechlivanos said.

The Walk draws from Richland, Ashland, Knox and Crawford counties. In Northwest Ohio, 32,000 people live with the fatal progressive brain disease and 96,000 family and friends care for them.

On Walk day, participants honor those affected by Alzheimers with the poignant Promise Garden ceremony a mission-focused experience that signifies solidarity in the fight against the disease. The colors of the Promise Garden flowers represent peoples connection to Alzheimers their personal reasons to end the disease.

The Alzheimer's Association has been a huge asset to many families," Benway said. "Our journey with Alzheimer's Disease and the Association began in 2001, when my mom began to suffer with memory issues.

"Through the years of her illness we relied heavily on the local Association for education, support groups, advocacy opportunities, and so much more. When we lost my mom in 2011, after 10 years with Alzheimer's, we stepped up our game and continued to support the Alzheimer's Association, and began to raise more money and more awareness through each Walk to End Alzheimers.

"My dad continues to support and educate so many friends who now are going through the caregiving journey which he did so well. Each time I share about my mom's journey, I am reminded of how important our work is, we must find a cure.

Area residents can go to alz.org/walk to sign up as a team captain, join a team or register to walk as an individual. Participants are encouraged to download the Walk to End Alzheimers mobile app to make their experience easier. Also, the FAQ page on alz.org/walk will be updated regularly for details on the Walk-day experience.

More than 6 million Americans are living with Alzheimer's disease a leading cause of death in the United States. Additionally, more than 11 million family members and

friends provide care to people living with Alzheimers and other dementias. The Alzheimers Association Walk to End Alzheimers, which helps all affected, is the worlds largest event to raise awareness and funds for Alzheimers care, support and research.

This year has been extremely stressful for all and thats why our efforts to raise money for care and support for local families are so critical," Pechlivanos said. "This Walk to End Alzheimers will be extra special because despite the pandemic, we now have a first-ever approved treatment for Alzheimers.

"The Walk will celebrate this advancement as well as acknowledge the extraordinary efforts of caregivers this past year.

Alzheimer's Association

The Alzheimers Association is a worldwide voluntary health organization dedicated to Alzheimers care, support and research. Its mission is to lead the way to end Alzheimer's and all other dementia by accelerating global research, driving risk reduction and early detection, and maximizing quality care and support. Visit alz.org or call 1-800-272-3900.

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Benway will chair the 2021 North Central Ohio Walk to End Alzheimer's - Richland Source

BioVie Presents Data Supporting use of NE3107 in the Treatment of Alzheimers Disease at 2021 Alzheimers Association International Conference – Yahoo…

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NE3107 Is the First Potentially Disease Modifying, Anti-Inflammatory Insulin Sensitizer Therapy In A Pivotal Phase 3 Trial

SANTA MONICA, Calif., July 27, 2021 (GLOBE NEWSWIRE) -- BioVie Inc., a clinical-stage company developing innovative drug therapies for the treatment of liver disease, neurodegenerative disease and certain cancers, announced today that a poster by Christopher L Reading, PhD, BioVies Executive Vice President for Neuroscience Research & Development was presented at the 2021 Alzheimers Association International Conference (AAIC).

Poster 55458 entitled Rationale for an anti-inflammatory insulin sensitizer in a phase 3 Alzheimers Disease trial highlighted the safety profile and broad mechanism of action against features of Alzheimers Disease of NE3107an oral small molecule, blood-brain permeable anti-inflammatory insulin sensitizer that binds ERK. NE3017 has also been shown to selectively inhibit inflammation-driven ERK- and NFB-stimulated inflammation without inhibiting their homeostatic functions. In prior animal studies and Phase 1 and 2 human clinical trials, NE3107 has been demonstrated to be safe and effective at reducing neuroinflammation and insulin resistance, both of which are recognized as important players in Alzheimers Disease pathology.

BioVie has obtained authorization from the U.S. Food & Drug Administration to initiate a pivotal Phase 3 trial of NE3107 in Alzheimers Disease called the NM101 study (NCT04669028). NM101 is a randomized double blind, placebo-controlled, US multicenter study of NE3107 in 316 subjects with mild to moderate Alzheimers Disease. In addition to conventional cognition, memory, functional, behavioral and imaging end points, NM101 will assess measures of glycemic control, brain glucose utilization and systems dysregulation. The basis for this study design was recently published in a peer-reviewed article in Neurodegenerative Disease Management (https://doi.org/10.2217/nmt-2021-0022). The study is actively recruiting and screening patients and aims to have data readout by the end of 2022.

Story continues

At the AAIC this year there are literally hundreds of presentations on inflammation and Alzheimers disease and dozens on insulin resistance and AD.

NE3107 is the first potentially disease modifying, anti-inflammatory insulin sensitizer therapy in a phase 3 trial, said Cuong Do, Chief Executive Officer of BioVie. Additionally, our NM101 study is the first randomized, double blind, placebo-controlled Phase 3 trial conducted by any company to test a disease modifying anti-inflammatory insulin sensitizer therapy in subjects with mild to moderate Alzheimers. NE3107 has been shown to decrease the inflammatory signal transduction cascades that are known to inhibit insulin action in the brain, and to restore insulin action. NE3107 blocks the major inflammatory nodes of extracellular signal-regulated kinase (ERK) and nuclear factor kappa B (NFkB). In addition, examples were presented to show that NE3107 preserves both ERK and NFkB homeostatic functions. We are initiating this trial with the aim of reading out the end of 2022.

The AAIC is being held virtually and in Denver, CO, July 26-30, 2021.

About BioVie

BioVie Inc. (NASDAQ: BIVI) is a clinical-stage company developing transformative therapies to overcome unmet medical needs in chronic debilitating conditions. In liver disease, the Companys Orphan drug candidate BIV201 (continuous infusion terlipressin), with FDA Fast Track status, is being evaluated in a US Phase 2 study for the treatment of refractory ascites with top-line results expected in early 2022. The Company is also planning a pivotal Phase 3 study of BIV201 in the treatment of hepatorenal syndrome-acute kidney injury (HRS-AKI). BIV201 is administered as a patent-pending liquid formulation. The active agent is approved in about 40 countries for related complications of advanced liver cirrhosis but is not available in the US or Japan. In neurodegenerative disease, BioVie recently acquired the assets of NeurMedix Inc., including NE3107, that binds to ERK and selectively reduces neuroinflammation and insulin resistance. Both are drivers of Alzheimers and Parkinsons diseases. The FDA has authorized a pivotal Phase 3 randomized, double blind, placebo controlled, parallel group, multicenter study to evaluate NE3107 in subjects who have mild to moderate Alzheimer's disease (NCT04669028). An estimated six million Americans suffer from Alzheimers. BioVie is planning to initiate this trial in mid-2021 and targeting primary completion in late 2022. A Phase 2 trial of NE3107 in Parkinsons Disease is planned for later this year, and related compounds have additional potential to treat certain cancers. NE3107 and related compounds are globally patented, first-in-class molecules. For more information, visit http://www.biovieinc.com.

Forward-Looking Statements

This press release contains forward-looking statements, which may be identified by words such as "expect," "look forward to," "anticipate" "intend," "plan," "believe," "seek," "estimate," "will," "project" or words of similar meaning. Although BioVie Inc. believes such forward-looking statements are based on reasonable assumptions, it can give no assurance that its expectations will be attained. Actual results may vary materially from those expressed or implied by the statements herein due to the Company's ability to successfully raise sufficient capital on reasonable terms or at all, available cash on hand and contractual and statutory limitations that could impair our ability to pay future dividends, our ability to complete our clinical trials and to obtain approval for our product candidates, to successfully defend potential future litigation, changes in local or national economic conditions as well as various additional risks, many of which are now unknown and generally out of the Company's control, and which are detailed from time to time in reports filed by the Company with the SEC, including quarterly reports on Form 10-Q, reports on Form 8-K and annual reports on Form 10-K. BioVie Inc. does not undertake any duty to update any statements contained herein (including any forward-looking statements), except as required by law.

Contact:INVESTOR RELATIONS:Bruce MackleManaging DirectorLifeSci Advisors, LLCbmackle@lifesciadvisors.com

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BioVie Presents Data Supporting use of NE3107 in the Treatment of Alzheimers Disease at 2021 Alzheimers Association International Conference - Yahoo...

KeifeRx Receives FDA Acceptance of Investigational New Drug for Phase 3 Study of Nilotinib BE in Early Alzheimer’s Disease – PRNewswire

Posted: at 1:54 am


WASHINGTON, July 30, 2021 /PRNewswire/ -- KeifeRx, LLC, an emerging clinical-stage biotechnology company specializing in the discovery and development of new treatment options for neurodegenerative diseases, announced today that the company received an acceptance of its Investigational New Drug (IND) application from the United States Food and Drug Administration (FDA) to launch a Phase 3 trial named NILEAD for Nilotinib BE.

The safety and efficacy of a Nilotinib BE will be investigated in individuals with dementia due to Alzheimer's disease with abnormal levels of brain amyloid and supporting clinical diagnosis of early Alzheimer's disease. "We are very pleased thatKeifeRx'sfirst IND has been accepted by the FDA," said Charbel Moussa, MBBS, PhD, Associate Professor at Georgetown University and Co-Founder and Director of KeifeRx's Scientific Advisory Board. "Our Phase 3 study provides us the opportunity to gain valuable insights about the potential effectiveness of Nilotinib BE in treating early Alzheimer's."

"We are excited about this major milestone for KeifeRx, and the chance to demonstrate the capabilities of our tyrosine kinase inhibitors (TKI) platform in neurodegeneration," said Chris Hoyt, CEO of KeifeRx. "We are looking forward to the successful execution of this program and the ability to help people affected by such a debilitating disease."

Alzheimer's disease is a disorder that affects over 6 million people in the United States and more than 44 million people worldwide.

About NILEAD:KeifeRx will launch a national, multicenter, placebo-controlled, double-blind study of Nilotinib BE in early Alzheimer's disease. A total of 1275 patients will be randomized into three groups (1:1:1) in which they will receive placebo or one of two doses of Nilotinib BE for 72 weeks. The primary objectives of the study are to investigate the safety and efficacy of Nilotinib BE on the progression of dementia in early Alzheimer's disease. A biomarker sub-study will investigate the effects of Nilotinib BE on amyloid brain burden as well as other makers of Alzheimer's pathology.

About KeifeRx: KeifeRx is clinical-stage life sciences company that focuses on a family of drugs called tyrosine kinase inhibitors (TKIs) that trigger degradation of malfunctioning proteins, mitigating their pathological toxic effects. Georgetown University owns several issued patents and pending patent applications on the underlying technology that relates to the use of TKIs for treatment of neurodegenerative diseases with Charbel Moussa as an inventor. KeifeRx has an exclusive option to license to the intellectual property from Georgetown University. KeifeRx was founded in 2019 to redefine the treatment experience for patients suffering from neurodegenerative diseases and movement disorders which include but are not limited to, Alzheimer's Disease, Lewy Body Dementia and Parkinson's Disease. KeifeRx is a DMV Angels backed company.

For more information on KeifeRx, please visit https://www.keiferx.com, https://www.linkedin.com/company/keiferx, or contact: Pasha Jahangiri, 202-810-0580, [emailprotected]

KeifeRx 1356 Beverly Road, Suite 300 McLean, Virginia 22101

SOURCE KeifeRx

http://www.keiferx.com

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KeifeRx Receives FDA Acceptance of Investigational New Drug for Phase 3 Study of Nilotinib BE in Early Alzheimer's Disease - PRNewswire

Lilly releases donanemab data that demonstrated relationship between reduction of amyloid plaque and slowing of cognitive decline | Antibodies | News…

Posted: at 1:54 am


DetailsCategory: AntibodiesPublished on Friday, 30 July 2021 10:50Hits: 599

- P-tau217 in blood showed promise as additional biomarker of efficacy

- Donanemab treatment led to 24% lowering of P-tau217 from baseline

INDIANAPOLIS, IN, USA I July 29, 2021 I Today at the Alzheimer's Association International Conference (AAIC 2021), Eli Lilly and Company (NYSE: LLY) presented two new exploratory analyses of data from the Phase 2 TRAILBLAZER-ALZ study. In the first, greater amyloid plaque changes following donanemab treatment was highly associated with less cognitive decline and participants with greater plaque clearance at 24 weeks of treatment showed less tau progression. In the second, Lilly shared data showing that treatment with donanemab drives a rapid reduction of a biomarker reflecting Alzheimer's disease pathology, plasma P-tau217, which was detected within 12 weeks.

Donanemab is an investigational antibody that targets a modified form of beta amyloid plaque called N3pG. In June 2021, Lilly announced the U.S. Food and Drug Administration (FDA) had granted Breakthrough Therapy designation for donanemab based on the Phase 2 data. No additional safety analyses were performed related to the presentations; for information on donanemab's safety profile, reference the previous publication.

"We are excited by these promising results, which provide further evidence on the potential for donanemab to slow disease progression for people with early symptomatic Alzheimer's disease," said Mark Mintun, M.D., vice president of pain and neurodegeneration, Lilly. "Importantly, these data link the mechanism of action of donanemab, plaque clearance, with positive effects on both clinical outcomes and brain tau pathology."

In the first oral presentation, donanemab induced rapid amyloid plaque reduction at 24 weeks in participants with early symptomatic AD, with the most rapid clearance in subjects with the most severe plaque burden at baseline.The subset of participants who reached complete amyloid plaque clearance at 24 weeks (defined as an amyloid level of <24.1CL)were able to stop or reduce dosing of donanemab earlier than other patients. Among those who achieved complete amyloid plaque clearance at 24 weeks and had a blinded switch to placebo, an exposure-response model showed minimal amyloid re-accumulation over the next year.

Additionally, among those who reached early complete amyloid plaque clearance status at 24 weeks, a flortaucipir positron emission tomography (PET) scan at 76 weeks showed a significant decrease of tau spread a predictive biomarker for AD progression over 76 weeks in frontal, parietal and temporal brain regions compared to placebo.

Greater amyloid plaque change at 24 weeks was also associated with improved Integrated Alzheimer's Disease Rating Scale (iADRS) score, a validated, composite measure that combines two well-established instruments used to assess cognition and daily function in AD clinical trials. Additionally, pharmacokinetic/pharmacodynamic modeling showed that greater relative amyloid plaque clearance was correlated with greater clinical benefit.

A second oral presentation focused on plasma P-tau217 (tau phosphorylated at threonine 217), a research blood-biomarker developed by Lilly, associated with amyloid and taupathology and diagnosis of Alzheimer's disease.Planned analyses showed that treatment with donanemab resulted in early reduction of P-tau217 (LS mean log10 change -0.04) and showed significant reduction (p<0.01) by the 3-month timepoint compared to placebo (LS mean log10 change 0). Decreased P-tau217 correlated significantly with amyloid change at all timepoints, at 24 weeks (R = 0.394, p<0.0001) and 76 weeks (R = 0.492, p<0.0001).

"Notably, these data support the amyloid cascade hypothesis and suggest that amyloid-related tauopathy can be altered with donanemab's impact on plaque clearance. Furthermore, the data support that early and profound amyloid clearance may translate into clinical benefit for patients," said John Sims, senior medical director of neurodegeneration and co-author of the analysis.

About DonanemabDonanemab is an investigational antibody that targets a modified form of beta amyloid plaque called N3pG. Results from a Phase 2 study of donanemab were announced and published earlier this year, and in June Lilly announced the U.S. Food and Drug Administration (FDA) had granted Breakthrough Therapy designation for donanemab based on the Phase 2 data. Lilly plans to submit a biologics license application (BLA) for donanemab under the accelerated approval pathway later this year.

About TRAILBLAZER-ALZIn the TRAILBLAZER-ALZ study, donanemab dosing was 700 mg every four weeks for the first three doses, then 1400mg every four weeks, for up to 76 weeks. Planned blinded dose reduction evaluations occurred at 24 and 52 weeks.

Donanemab is also being studied in the ongoing Phase 3 TRAILBLAZER-ALZ 2 study in early, symptomatic Alzheimer's disease patients. TRAILBLAZER-ALZ 3, a prevention study, will evaluate whether treatment with donanemab can prevent the clinical progression of Alzheimer's disease in trial participants before clinical impairment begins. Visit LillyMemoryTrials.comfor additional information on enrolling in Alzheimer's disease trials.

About Alzheimer's DiseaseAlzheimer's disease is a fatal illness that causes progressive decline in memory and other aspects of cognition. Dementia due to Alzheimer's disease is the most common form of dementia, accounting for 60 to 80 percent of all cases.1 There are currently over 50 million people living with dementia around the world, with numbers expected to increase to nearly 152 million by 2050.2Almost 10 million new cases of dementia are diagnosed each year worldwide, implying one new case every 3 seconds, and a significant increase in the caregiving burden placed on society and families.In the US alone, there was an increase of 8 million new caregivers from 2015 to 2020.3 The current annual societal and economic cost of dementia is estimated at $1 trillion, an amount that is expected to double by 2030 unless we find a way to slow the disease.2

In an addition to age and family history of AD, the greatest risk factor for developing AD is the presence of the apolipoprotein E 4 (APOE4) allele.1 Having one APOE4 allele increases the risk of developing Alzheimer's disease by approximately three times compared with those with two copies of the APOE3 form. Those who inherit two copies of the APOE4 allele have an 8 - 12-fold risk. In addition, those with the APOE4 allele are more likely to have beta-amyloid accumulation and Alzheimer's dementia at a younger age than those with the APOE2 or APOE3 forms of the APOE gene.

AboutEli Lilly and CompanyLilly is a global healthcare leader that unites caring with discovery to make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit us at lilly.comand lilly.com/newsroom. P-LLY

SOURCE: Eli Lilly

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Lilly releases donanemab data that demonstrated relationship between reduction of amyloid plaque and slowing of cognitive decline | Antibodies | News...

Alzheimer’s Facts and Figures Report | Alzheimer’s Association

Posted: July 19, 2021 at 1:54 am


Quick Facts

MORE THAN 6 MILLION AMERICANS ARE LIVING WITH ALZHEIMER'S. BY 2050, THIS NUMBER IS PROJECTED TO RISE TO NEARLY 13 MILLION.

IN THE UNITED STATES, ALZHEIMERS AND DEMENTIA DEATHS HAVE INCREASED 16% DURING THE COVID-19 PANDEMIC.

1 IN 3 SENIORS DIES WITH ALZHEIMER'S OR ANOTHER DEMENTIA. IT KILLS MORE THAN BREAST CANCER AND PROSTATE CANCER COMBINED.

IN 2021, ALZHEIMER'S AND OTHER DEMENTIAS WILL COST THE NATION $355 BILLION. BY 2050, THESE COSTS COULD RISE AS HIGH AS $1.1 TRILLION.

MORE THAN 11 MILLION AMERICANS PROVIDE UNPAID CARE FOR PEOPLE WITH ALZHEIMER'S OR OTHER DEMENTIAS.

IN 2020, THESE CAREGIVERS PROVIDED AN ESTIMATED 15.3 BILLION HOURS OF CARE VALUED AT NEARLY $257 BILLION.

ONLY 53% OF BLACK AMERICANS TRUST THAT A FUTURE CURE FOR ALZHEIMERS WILL BE SHARED EQUALLY REGARDLESS OF RACE, COLOR OR ETHNICITY.

3 IN 10 HISPANICS DO NOT BELIEVE THEY WILL LIVE LONG ENOUGH TO DEVELOP DEMENTIA.

BETWEEN 2000 AND 2019, DEATHS FROM HEART DISEASE HAVE DECREASED 7.3% WHILE DEATHS FROM ALZHEIMER'S HAVE INCREASED 145%.

The number of Americans living with Alzheimer's is growing and growing fast. More than 6 million Americans of all ages have Alzheimer's.

An estimated 6.2 million Americans age 65 and older are living with Alzheimer's dementia in 2021. Seventy-two percent are age 75 or older.

As the number of older Americans grows rapidly, so too will the number of new and existing cases of Alzheimer's. By 2050, the number of people age 65 and older with Alzheimers dementia may grow to a projected 12.7 million, barring the development of medical breakthroughs to prevent, slow or cure Alzheimers disease.

Alzheimers is not just memory loss. Alzheimers kills.

People age 65 and older survive an average of four to eight years after a diagnosis of Alzheimers dementia, yet some live as long as 20 years with Alzheimers. This reflects the slow, uncertain progression of the disease.

Eighty-three percent of the help provided to older adults in the United States comes from family members, friends or other unpaid caregivers. Nearly half of all caregivers who provide help to older adults do so for someone living with Alzheimer's or another dementia.

Who are the caregivers?

Of the total lifetime cost of caring for someone with dementia, 70% is borne by families either through out-of-pocket health and long-term care expenses or from the value of unpaid care.

The costs of health care and long-term care for individuals living with Alzheimers or other dementias are substantial, and dementia is one of the costliest conditions to society.

In 2021, Alzheimer's and other dementias will cost the nation $355 billion, including $239 billion in Medicare and Medicaid payments combined. Unless a treatment to slow, stop or prevent the disease is developed, in 2050, Alzheimer's is projected to cost more than $1.1 trillion (in 2021 dollars). This dramatic rise includes more than three-fold increases both in government spending under Medicare and Medicaid and in out-of-pocket spending.

Despite decades of research and calls to action to ensure that health care is accessible and equal for all regardless of gender, race, ethnicity, geography and socioeconomic status, that aim is still far from reality for too many Americans, as the Alzheimers Association Race, Ethnicity and Alzheimers in America special report shows:

These findings suggest there is a lot of work ahead to achieve better health equity. Paths forward include:

The 2021 Alzheimer's Disease Facts and Figures report contains data on the impact of this disease in every state across the nation. Click below to see the effect that Alzheimer's is having in your state.

See the article here:
Alzheimer's Facts and Figures Report | Alzheimer's Association

Alzheimer’s Disease Symptoms – Psych Central

Posted: at 1:54 am


Alzheimers disease is a neurocognitive disorder (either major or minor, depending upon its severity) that has a subtle onset and is characterized by a gradual progression in cognitive impairment.

The specific symptoms of Alzheimers disease are:

1. The criteria are met for either major neurocognitive disorder or minor neurocognitive disorder.

2. There is subtle onset and gradual progression of impairment in one or more cognitive domains (for major neurocognitive disorder, at least two domains must be impaired).

3. The following criteria are also met.

For major neurocognitive disorder

For minor neurocognitive disorder

The cognitive deficits each cause significant impairment in social or occupational functioning and represent a significant decline from a previous level of functioning. The course is characterized by gradual onset and continuing cognitive decline. The deficits do not occur exclusively during the course of a delirium.

The cognitive deficits above are not due to any of the following:

Updated for the DSM-5.

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Alzheimer's Disease Symptoms - Psych Central

Alzheimer’s Disease Research Center (ADRC), University of …

Posted: at 1:54 am


The UW Alzheimers Disease Research Center (ADRC) is one of a nationwide network of 30 research resource centers funded by the National Institute on Aging. ADRCs are major sources of discovery into the nature of Alzheimers disease and related dementias and into the development of more effective approaches to prevention, diagnosis, care, and therapy. The UW ADRC contributes to the development of shared resources that support dementia-relevant research, and coordinates research efforts with other NIH-funded programs and investigators. UW ADRC resources are designed to facilitate and empower related research efforts at UW.

The UW ADRC is closely affiliated with the UW Memory and Brain Wellness Center clinic and links the Seattle community with information and opportunities to participate in studies of Alzheimers disease and related disorders (Lewy Body dementia, and frontotemporal degeneration, and vascular dementia). Our busy outreach team is influential in promoting strengths-based reframing of Alzheimers disease and dementia-friendly communities, and they organize and promote educational public talks and events and research seminars. We support outreach and culturally adapted Alzheimers disease programs for Indigenous communities and clinics. Join us!

Director: Dr. Thomas J. Grabowski, MDProgram Manager: Annika Noreen, PhD, PMP

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Alzheimer's Disease Research Center (ADRC), University of ...

CMS to Conduct NCD Analysis on Treatment for Alzheimer’s Disease – RCPA

Posted: at 1:54 am


Today, the Centers for Medicare and Medicaid Services (CMS) announced they will be opening a National Coverage Determination (NCD) analysis on the treatment for Alzheimers disease. This NCD process will allow CMS to carefully review and determine whether Medicare will establish a national Medicare coverage policy for monoclonal antibodies targeting amyloid for the treatment of Alzheimers disease. NCDs are program instructions developed by CMS to describe the nationwide conditions for Medicare coverage for a specific item or service. This NCD analysis will be applicable to national coverage considerations for aducanumab, which was recently approved by the Food and Drug Administration (FDA), as well as any future monoclonal antibodies that target amyloid for the treatment of Alzheimers disease.

Currently, coverage determinations for aducanumab are being made at the local level by Medicare Administrative Contractors (MACs) who represent 12 jurisdictions across the country. CMSs coverage decisions are based on careful analysis of the evidence and benefits a given therapy provides to Medicare beneficiaries. To determine whether a national policy is appropriate, CMS will follow a standard process that includes multiple opportunities for the public to participate and present comments through both listening sessions and the CMS Coverage website. The analysis will determine whether the evidence meets the Medicare laws requirements that items or services be reasonable and necessary for the diagnosis or treatment of illness or injury. To make this determination, CMS uses a formal process established by statute. The process includes an assessment of the clinical evidence such as published clinical studies, professional society guidelines, and public comments to determine coverage.

Following this analysis, CMS will post a proposed NCD, which will be open to a second 30-day public comment period. After reviewing all comments received on a proposed determination, CMS will announce its final decision for a national policy which could range from Medicare coverage of this product type, coverage with evidence development, non-coverage, or deference to the Medicare Administrative Contractors. A proposed decision is expected to be posted within 6 months and a final within 9 months.

As part of the NCD process, a 30-day public comment period will begin today. CMS will also host two public listening sessions in July to provide an opportunity for public input.

To register for the listening sessions:July 22, 2021 from 9:00 am11:00 am (EDT) orJuly 27, 2021 from 2:00 pm4:00 pm (EDT)

NCDs are posted on the CMS Medicare Coverage Center website and provide stakeholders with the Medicare coverage criteria, a summary of the evidence considered, and CMSs rationale for the decision. Comments can be submitted and viewed here.

Excerpt from:
CMS to Conduct NCD Analysis on Treatment for Alzheimer's Disease - RCPA

New book offers valuable insight for caregivers of those with Alzheimer’s disease – Albany Times Union

Posted: at 1:54 am


Fifteen years ago, when the doctor informed Maryanne Scott that her father, Sam Valenti, was suffering from the early stages of Alzheimers disease, she was unclear what that meant.

Today theres a lot of news about Alzheimers, but it wasnt like that 15 years ago, said Scott from her home in Doylestown, Pa. After the doctor said that, I asked what this meant. I wanted to know how we could cure it, but he informed me there was no cure and that it was a progressive degenerative disease.

Alzheimers would ultimately take her and her younger brother Sam on an eight-year journey of caring for their beloved dad. It also led to her first book, An Eight Year Goodbye: A Memoir.

As she writes in her book, There are over five million Americans living with Alzheimers disease today and over sixteen million caregivers riding this emotional roller coaster. These caregivers are also saying goodbye to their loved ones, a long, painful goodbye. Ive been in those shoes.

Scott, who lived in Clifton Park 2o years ago before moving to Doylestown, wrote the book as a form of therapy. She never intended to publish it.

"After my dad died I began seeing a counselor who told me to write down all my feelings of guilt. I wondered if I had done enough for him, she said.

Her counselor said Scott was suffering post-traumatic stress disorder. She said for eight years I had been focusing on a battle with Alzheimers. I had never had any time to focus on much of anything else, and after it was over everything came crashing down. So I wrote down all my feelings, the anger and the guilt. It felt good to get that all out of me.

The more Scottwrote, the more she began to think her words might be helpful for someone else going through the trauma she and her brother had experienced.

I had nowhere to turn 15 years ago when my dad was first diagnosed. There were books about the symptoms of the disease, but I needed someone to tell me it was normal to feel impatience, despair and loneliness when caring for someone like my dad. Its a lonely battle to be a caregiver, and I hope this book can help others going through this.

She wrote the book in sections, rather than in chronological order. It took me a long time to write this book because I was reliving these painful events. I would often start crying and have to put the writing away only to return to it a month or so later. Sometimes Id write about some lighter moments that happened, just so the book wouldnt be as depressing like the time near the end when dad was not very responsive and I wanted to play a beautiful song that he used to play for me when I was 12 years old. It was the song he played when he taught me how to dance, but inadvertently the song Im on the Highway to Hell by AC/DC came out of the speaker. As my brother would often say, If we dont laugh, well cry.

Scott wrote the book to help other caregivers going through this, and to pay tribute to her dad.

He was such an honorable man, she said. He served his country in World War II, loved his family with all his heart, worked hard to support his family, and even at the end he never lost his sense of humor, his dignity or his kindhearted nature.

Her book contains valuable information for caregivers on navigating ones way through Alzheimers from its early stages to the final stages when those with the disease are often incontinent, unable to talk or even swallow.

Early on, families need to get some sort of in-home care. You cannot possibly do this on your own. There may also be days when you need to take a break and regroup. My brother and I were so lucky to have each other.

Scott's advice for a family considering an assisted-care facility is to be a squeaky wheel. When dad could no longer stay in his home we found a place for him, and Im not so sure they liked me because I visited almost every day and expected a certain level of care for my dad. Some families drop off the aging parent and never visit. My brother and I made sure he had the best care possible, received his newspaper every day, had clean sheets in his bed and was treated with respect.

Being with her dad in the last days of his life enriched Scott's spiritual faith. There was a certain peace that came over him in his last days. He was mostly unresponsive, but we could hear him talking to his brother Joe, who had died years ago. He was asking Joe what it was like up there. Once he wanted to know what was on my shoulder. It was like there was an angel there, and when I told him it was OK for him to go, that he could see Mom again, he smiled, and I felt like somebody was there taking him. The room itself just felt so calm.

One of the many things she learned from writing this book is that she is much stronger than she ever thought. There were times when I didnt know how much longer I could sustain this. During that eight-year period, my husband had a spinal cord injury, I had two teenagers at home, my son was going off to college, and I didnt know where to turn for support. My brother and I look back now and dont know how we did it, but we got the strength from somewhere. I guess when a loved one is suffering, you somehow rise to the challenge to care for them.

"An Eight Year Goodbye: A Memoir" (Page Publishing, $16.95) can be found online and at The Book House in Stuyvesant Plaza, I Love Books in Delmar, Northshire Bookstore in Saratoga Springs and Barnes & Noble in Colonie.

See more here:
New book offers valuable insight for caregivers of those with Alzheimer's disease - Albany Times Union

Therapy and prevention of Alzheimer’s disease | NDT – Dove Medical Press

Posted: at 1:54 am


Introduction

Amyloid- (A) in the brain is a causative protein of Alzheimers disease (AD). Harmful proteins primarily include 40 amino-acid A140, 42 amino-acid A142, and abnormally phosphorylated tau.1 Impaired A clearance from the brain might increase brain A, particularly in sporadic AD cases. A clearance from the brains of patients with sporadic AD was 30% lower than the clearance in normal subjects, although A production was similar.2 The peripheral administration of anti-A antibodies to increase the clearance of As from the brain has been investigated. Unfortunately, most clinical trials using anti-A antibodies did not meet the endpoint criteria, although brain As were reduced. However, a recent re-analysis of the clinical results for Aducanumab, an anti-A antibody, revealed reduced cognitive decline at the high dose,3 resulting in the accelerated approval of an Alzheimers drug by the FDA on June 7, 2021. Furthermore, Gantenerumab, an anti-A antibody used in the dominantly inherited Alzheimers network trial unit (DIAN-TU), reduced As and tau in the brain.4,5 Therefore, A may be the primary causative protein for AD.4

We proposed extracorporeal blood A removal systems (E-BARS) as another method for enhancing A clearance from the brain (Figure 1).6 There are several rationales for blood A removal systems. First, there is an A concentration gradient between the brain and blood. A concentration in the cerebrospinal fluid (CSF) of patients with AD is approximately 100 times higher than in the plasma.7,8 Second, A moves from the brain into the blood via transporters, including low-density lipoprotein receptor-related protein 1 (LRP-1), ApoJ, ApoE, and receptor for advanced glycation end products (RAGE).911 Pharmaceuticals targeting RAGE and LRP-1 are being developed to increase A transportation.12

Figure 1 Schematic diagram of the extracorporeal blood A removal systems (E-BARS) using HexDC or the PSf dialyzer. Postulated mechanisms for the E-BARS include: 1) HexDC and/or PSf hemodialyzer remove blood As in an extracorporeal circulation system, 2) rapid decrease in plasma As, and 3) it triggers increased A influx from the brain into the blood, resulting in retention or improvements of Alzheimers disease.

We have reported the following evidence to support the efficacy of blood A removal for AD therapy and prevention. First, we found several medical materials of high efficacy for A removal from the blood, including hexadecyl alkylated cellulose beads (HexDC)6,13 and hollow fibers in hemodialyzers, such as polysulfone (PSf), polymethylmethacrylate, and polyethersulfone.14 The A removal efficiency of PSf dialyzers was as high as 50% for both A140 and A142 during a 4 h hemodialysis session.15,16 The mechanism of blood A removal by these hemodialyzers is mainly by adsorption.14,17 Second, the removal of blood A evoked a large influx of A into the blood from certain tissues during hemodialysis.15,16,18,19 Third, we showed that A accumulation in the brains of patients undergoing hemodialysis was significantly lower than A accumulation in age-matched controls not undergoing hemodialysis.20 Furthermore, we reported more direct evidence showing that hemodialysis decreased A accumulation in the brain by positron emission tomography (PET)-imaging with Pittsburgh compound B (PiB) as a probe (PiB/PET).21 The brain A accumulation in a chronic renal failure patient suffering from mild cognitive impairment was decreased by 0.19 standard uptake value ratio (SUVR) after hemodialysis for 6 months (4 h/session, three sessions/week). The data suggest that the brain is an origin of A influx into the blood during hemodialysis. Fourth, A concentration in the CSF was decreased in rat studies using HexDC columns. Plasma A concentrations increased during blood A removal, despite the 90% efficiency of A removal using HexDC columns.22 Finally, the mini-mental state examination scores of hemodialysis patients were maintained or slightly improved in a prospective study.18 We also reported that longer hemodialysis duration correlated with lower dementia risk in an analysis of more than 200,000 Japanese hemodialysis patients.23 Furthermore, we recently reported that A oligomers were effectively removed by size-separation methods with hollow fiber devices of appropriately large pore sizes in vitro and in humans.24

Several other groups also reported that removing blood As may be a helpful AD therapy. Peritoneal dialysis, in which peritoneal membranes are used as dialysis membranes instead of hemodialyzers, reduced plasma A in humans and brain A in mouse AD models.25 The authors reported that peritoneal dialysis only removed 131.33 ng of As,25 whereas hemodialysis removed 7219 ng of A140 and 664 ng of A142, totaling 7883 ng of As as we reported previously.19 Furthermore, plasma exchange therapy, which removes plasma A by discarding the plasma with albumin replacement as A binding protein, effectively improves cognitive functions in patients with AD.26 This therapeutic plasma exchange discarded all plasma proteins, including coagulation factors and immunoglobulins. Therefore, intravenous immunoglobulin was injected every 4 months.

Thus, the removal of blood A has attracted attention as a therapeutic strategy for AD.27

Furthermore, regarding A influx into the blood, we reported that the total amount of A influx during one hemodialysis session (4 h) was calculated as 7219 ng for A140 and 664 ng for A142 for 30 patients undergoing hemodialysis.19 These amounts of A influx during one hemodialysis session of 4 h are comparable with the reported total A content of 7760 ng in the brain.28

We found several effective materials suitable for blood A removal, including HexDC and PSf-HFs. This study aimed to determine which materials are more efficient at removing As from the blood (Figure 1). Another and primary objective in this study was what systems are more effective to evoke a larger A influx into the blood. We compared two systems: one was a system of enhanced A removal activity by using doubled A removal devices (concomitant use of HexDC and PSf hemodialyzer) for 4 h, the other was a longer treatment system by using PSf hemodialyzer alone for 8 h.

This study conformed to the Declaration of Helsinkis Good Clinical Practice. This research was comprehensively reviewed and approved by the institutional review board at Fujita Health University (the latest approval number is HM16-266). Patients undergoing blood purification provided written informed consent for collecting blood samples.

Human plasma remaining in used bags of fresh frozen plasma and discarded plasma from patients was obtained after plasma exchange therapy. The plasma was refrozen at 80C with additional heparin. Before use, the plasma was thawed and shook in a water bath at 37C and centrifuged to remove precipitates. Detailed procedures were previously described.24

HexDC was chosen for this study because it is one of the most efficient adsorbents for blood A removal, as described in the Introduction.6,13 HexDC beads, shown in Figure 2A, came from a commercially available HexDC device (LIXELLE S-35 containing 350 mL HexDC, Kaneka, Osaka, Japan), which is used to remove 2-microglobulin from the blood of hemodialysis patients having carpal tunnel syndrome in the clinical circuit with tandem connection to hemodialyzers. Hexadecyl alkyl chains are appropriately hydrophobic, interacting with hydrophobic proteins, such as 2-microglobulin and As. HexDC beads (1.75 mL, 1/200 of LIXELLE S-35) were put into a 2.5 mL polypropylene syringe to form the mini-HexDC column.

Figure 2 Materials for A removal: hexadecyl alkylated cellulose beads (HexDC) and polysulfone hollow fibers (PSf-HF) fragments were used for A removal in this study. (A) HexDC: bottom, the chemical structure of HexDC; top left, a photo of HexDC beads; top right, enlarged HexDC photo. (B) Fragments of PSf-HF: bottom, the chemical structure of polysulfone; lower middle, PSf hemodialyzer; upper middle, PSf hollow-fiber bundles as main components of the PSf hemodialyzer; top left, a photo of PSf-HF fragments of 25 mm length which were cut from PSf-HF bundles; top right, enlarged photo of PSf-HF fragments.

PSf-HFs were also used in this study as one of the most efficient adsorbents for blood A removal.1417 Among various materials of hollow fibers in hemodialyzers, PSf is hydrophobic enough to adsorb hydrophobic proteins, such as albumin and As. PSf-HF was obtained from hemodialyzers (APS-13EA, Asahi Kasei Medical, Tokyo, Japan) and cut into 25 mm fragments (Figure 2B) to eliminate the filtration effect. The membrane surface area of the fragments in the mini-column of PSf-HF was 0.01 m2, which was 1/200 of 2.0 m2 (a representative membrane area used in clinical hemodialysis). The fragments were put into a 2.5 mL syringe to form a mini-column of PSf-HF fragments.

Eighteen milliliters of pooled human plasma was applied continuously to mini-columns of HexDC or PSf-HF fragments and returned to the plasma pool at a flow rate of 240 L/min using a Perista pump (ATTO, Tokyo, Japan), as shown in Figure 3A. This plasma flow rate was set to 1/200 of the flow rate in a clinical setting with 50 mL plasma/min (77 mL blood/min when the hematocrit is 35%), determined in our previous study.14

Figure 3 Experimental and clinical circuits of A removal systems. (A) In vitro experimental circuit for A removal with mini columns of HexDC or PSf-HF fragments. Plasma flow rate and the quantities of HexDC or PSf HF were set to 1/200 of the human clinical setting. A removal efficiencies of the columns and reduction rates in the plasma pool are defined in Eqs (1) and (2), respectively. (B) The basic concept of adsorptive filtration system for A removal to enhance adsorption to the inner surface of hollow-fiber walls in hemodialyzers. (C) One-pump adsorptive filtration circuit with a Venturi tube and PSf hemodialyzer. (D) The clinical setting for treatment of renal failure patients suffering from carpal tunnel syndrome as a complication. The PSf hemodialyzer was tandemly connected just after the HexDC column (pale green background). (E) The clinical setting for treatment of renal failure patients with a PSf hemodialyzer (light orange background).

The A removal efficiency of the column was calculated as follows:

The A reduction rate for the experimental pool solution was defined as follows:

The primary mechanism of A removal using hemodialyzers is adsorption, not filtration.14 To enhance adsorption to the surface of micropores in the hollow fiber walls of hemodialyzers (Figure 3B), we developed adsorptive filtration systems with two pumps.17 One pump is for blood circulation and the other for filtration. In this study, to make adsorptive filtration systems with two pumps easier to use in clinical settings, one-pump adsorptive filtration systems were created with Venturi tubes instead of filtration pumps (Figure 3C). The Venturi tube has a narrow pass in the middle part, which increases fluid pressure before the narrow pass and decreases the pressure after the narrow pass. The increased fluid (blood) pressure enhances filtration through the wall of hollow fiber membranes in adsorptive filtration systems.

The Venturi tubes were designed with three-dimensional computer-aided design software, DesignSpark Mechanical (RS Components, Yokohama, Japan). Using the designed standard triangulated language (STL) data, Venturi tubes were produced with 1.75 mm filaments of polylactic acid using a fused deposition modeling 3D printer (Replicator 2; MakerBot, NY, USA). In the experimental circuit (Figure 3C), a Venturi tube was added after the polysulfone dialyzer outlet (APS-13EA, Asahi Kasei Medical, Tokyo, Japan) to control the filtration rate. A flowmeter (Coriolis Flow Meter FD-SS02A, Keyence, Osaka, Japan) was placed between the filtrate outlet (one of the dialysate ports) and the junction with the return tube to the pool of 250 mL of human plasma. Human plasma was circulated at a 50 mL/min flow rate using peristaltic pumps (Masterflex Variable-Speed Drive; Cole-Parmer, IL, USA). This flow rate was determined based on our previous studies of adsorptive filtration.14,17

Table 1 summarizes the demographics of the blood treatment subjects. All subjects were nondiabetic, as diabetes mellitus is an AD risk factor. Three hemodialysis patients having carpal tunnel syndrome underwent treatment using PSf hemodialyzers (APS-21SA, Asahi Kasei Medical, Tokyo, Japan) and tandemly connected HexDC (LIXELLE S-15, Kaneka, Osaka, Japan). Figure 3D shows the clinical circuit for these treatments. Treatment time was 4 h, and patients were treated during the day. Dialysate flowed outside PSf-HF in the PSf hemodialyzer at a flow rate of 500 mL/min.

Table 1 Demographics of the Subjects Undergoing Blood Purification

This treatment system can be regarded as a kind of E-BARS with double A-removal devices (concomitant use of HexDC and PSf hemodialyzer). Furthermore, PSf hemodialyzer in this system worked as an adsorptive filtration system14,17 because of water removal by filtration. Hemodialysis patients can pass little or no urine because of renal failure; excess water by drinking and eating should be removed from the blood during hemodialysis. The filtration rate for the removal of excess water from the blood was approximately 10 mL/min (Figure 3D).

Three additional patients were treated using only PSf hemodialyzers (APS-21SA) for 8 h overnight because they had daytime jobs. Figure 3E shows the clinical circuit. Dialysate flowed outside PSf-HF in the PSf hemodialyzer at a flow rate of 400 mL/min. This treatment system can be regarded as longer time treatment of E-BARS. The first 4 h of hemodialysis in these patients was regarded as the hemodialyzer-only (without HexDC) control group compared with concomitant treatments with HexDC and hemodialyzer. Filtration rates of the hemodialyzers were 69 mL/min for removal of excess blood water (Figure 3E).

Blood samples were obtained at 0, 1, and 4 h (for all patients) and 8 h (for ON13 patients in Table 1). The dialysate flow rate was 400 mL/min (24 L/h) for ON13 patients (Table 1). Part of the mixture of filtrate and discarded dialysate were collected at the rate of 1 L/h for the periods of 04 h and 48 h for ON13 patients. The accumulated filtrate/dialysate was mixed well before sampling.

A influx into the plasma during blood treatment was estimated as the sum of As changed in the plasma during blood treatments and As removed by dialyzers, HexDC, or both, according to the following equation.

where A removed by a device during the period=(concentration of A at the inlet of a device) X (removal efficiency of the device) X (plasma flow rate during the period) X (minutes of the period)

Decreased plasma concentration is denoted with a minus sign. The period is divided into 01, 14, and 48 h of a treatment session. A concentration at the devices inlet was set as the average of each period: 0 and 1 h for the 01 h period, 1 and 4 h for the 14 h period, and 4 and 8 h for the 48 h period. The removal efficiency of the devices for the 01 h was the removal efficiency at 1 h. The removal efficiency for the 14 h period was the average of those at 1 and 4 h, and the removal efficiency for the 48 h period was the average of those at 4 and 8 h. The whole blood volume was calculated as 1/13 of the patients body weight. The plasma volume was calculated as (whole blood volume) (1 hematocrit/100).

A1-40 and A1-42 concentrations in the plasma were measured using the High-Sensitive Human Amyloid (140) and (142) ELISA Kit Wako II (WAKO Pure Chemical, Osaka, Japan), respectively. ApoE4 was measured by the ApoE4/Pan-ApoE ELISA kit (MBL, Nagoya, Japan).

All data are expressed as the mean standard deviation unless otherwise specified. Differences were determined using a Wilcoxon rank-sum test for nonparametric variables and the Students t-test for parametric variables, unless otherwise specified, using the statistical package JMP14 (SAS Institute Inc., Cary, USA). Values of p < 0.05 were considered statistically significant.

The in vitro A removal efficiencies and reduction rates for HexDC were compared with PSf-HFs using mini-columns. Figure 3A shows the experimental circuit; quantities of HexDC and PSf-HF and the plasma flow rates were set at about 1/200 of the parameters used in clinical patient treatment. PSf-HF fragments of 25 nm length were packed in the column to eliminate the filtration effect and detect adsorption effects only.

A140 and A142 in the plasma pool were significantly decreased to about half of the initial concentrations by HexDC and PSf-HF fragment columns (solid lines in Figure 4AD). The A140 and A142 concentrations at the HexDC columns outlet (Post) were almost zero during the treatment period, indicating that almost all As flowing into the column were removed by the HexDC columns (dotted lines in Figure 4A and C). By contrast, A concentrations at the outlet (Post) of PSf-HF fragment columns gradually increased after 30 min of treatment, especially the A140 (dotted lines in Figure 4B and D). The A140 concentrations at the outlet (Post) were similar to those in the plasma pool (Pool) at 60 min (Figure 4B), indicating that PSf-HF fragments removed almost no A1-40 at the end of the treatment.

Figure 4 A concentration changes in the plasma pool and post-filtration for the mini columns in vitro. (A and B) A1-40 (blue) concentration changes with mini columns of HexDC (A) and PSf-HF fragments (B). (C and D) A1-42 (red) concentration changes with HexDC (C) and PSf-HF Fragments (D). Solid lines with circle symbols, in the plasma pool; Dotted lines with square symbols, post-filtration (at the outlet of mini columns). ns, not significant, *p < 0.05; **p < 0.01; and ***p < 0.001 indicate significant changes compared with 0 min for the plasma pool and with 15 min for the post-filtration measurements).

Figure 5A and B for A140 and Figure 5C and D for A142 show the removal efficiencies for the mini-columns and reduction rates in the plasma pool. Using HexDC, the removal efficiencies for both As were approximately 100% during the entire treatment period (dashed line in Figure 5A and C). However, the removal efficiencies and reduction rates decreased after 30 min treatment using the PSf-HF fragments. The A140 removal efficiency was significantly lower using the PSf-HF fragments than the removal efficiency using HexDC (Figure 5A, p < 0.01). The A140 removal efficiency at 60 min using PSf-HF fragments was below zero, indicating that some adsorbed A140 was desorbed at the end of the treatment. In contrast to the removal efficiencies, the reduction rates increased for both materials and reached more than 50% after 60 min of treatment (Figure 5B and D). Thus, more than half of the existing As in the plasma pool were removed after 60 min of treatment. The A140 reduction rates after 60 min of HexDC treatment were significantly higher than the reduction rates when using PSf-HF fragments because of the higher removal efficiency (Figure 5B, p < 0.05).

Figure 5 A removal efficiencies and reduction rates for the in vitro systems using HexDC or PSf-HF fragments. (A and B) A1-40 (blue) removal efficiency (A) and reduction rate (B). (C and D) A1-42 (red) removal efficiency (C) and reduction rate (D). Dashed line with rhombus symbols represent HexDC; dotted line with square cross marks represent PSf-HF fragments. (*p < 0.05; **p < 0.01; and ***p < 0.001 indicate significant changes compared with 0 min). Removal efficiencies of HexDC were significantly higher than those of PSf-HF fragments for A1-40 at 60 min (p < 0.01) (A). Reduction rates of HexDC were significantly higher than those of PSf-HF fragments for A1-40 at 60 min (p < 0.05) (B).

Adsorption on the surface of the small inner pores in the walls of hollow fibers was enhanced by filtration to increase the A removal activity of PSf-HF (adsorptive filtration, Figure 3B). The previous adsorptive filtration was conducted using two pumps, a main blood circulation pump and a filtration pump through the hollow fiber walls.17 The representative clinical setting of the two-pump adsorptive filtration system is similar to that in Figure 3E, but no dialysate. A one-pump system was created to make this adsorptive filtration easy to use. The basic concept of this system was that the pressure changes in the Venturi tubes at the outlet of the dialyzer increase filtration through the hollow fibers membrane walls. Venturi tubes with various minimum internal diameters were produced using a 3D printer (Figure 6A and B). When melted PLA filaments were piled in the long axis direction (Figure 6C), the cross sections were not circular in parts, resulting in frequent leakage at the circuit tube connections. Melted PLA filaments were then piled circumferentially (Figure 6D), resulting in less leakage.

Figure 6 Preparation of Venturi tubes for the one-pump adsorptive filtration system. (A and B) Design and dimensions of the Venturi tubes. Melted PLA filaments were piled in the long axis direction (C) or circumferentially (D). The latter resulted in less leakage.

Abbreviations: o.d., outer diameter; i.d., internal diameter; Min, minimum; Max, maximum.

Circulation analysis using these Venturi tubes was first conducted using water (Figure 7A). As expected, the filtration rate (QF) depended on the tubes narrowest inner diameter and the flow rate (QB) of water. This one-pump adsorptive filtration system was then applied to A removal from human plasma with PSf hemodialyzers for 60 min (Figure 3C). The pressures before and after the hemodialyzer and at the filtrate outlet were mostly stable throughout the 60 min sessions at 50 mL/min QB (Figure 7B, an example using the Venturi tube 14j-2, whose minimum internal diameter was 1.4 mm). The A reduction rates in the plasma pool were high, as shown in Figure 7C and D for A140 and A142, respectively. Thus, the one-pump system functioned as designed.

Figure 7 Performance of the one-pump adsorptive filtration system with Venturi tubes. (A) Correlation between the narrowest internal diameter (i.d.) and flow rate (QB) measured with water. At 50 mL/min QB, suitable filtration rate (QF) (around 610 mL/min) was obtained with an i.d. of 1.42.5 mm. (B) Representative data for stable QF (mL/min) and pressures (kPa) at Pre (the inlet of hemodialyzers), Post (the outlet of Venturi tubes connected to hemodialyzers), and Filtrate of PSf hemodialyzer during A reduction from human plasma with the 14j-2 Venturi tube of 1.4 mm i.d. (C and D) Reduction rates of plasma A1-40 (C) and A1-42 (D) in the human plasma pool for three Venturi tubes. **p < 0.01.

To enhance A influx into the blood, an E-BARS with double A removal devices seemed effective. We hypothesized that concomitant use of a HexDC column and a PSf hemodialyzer (double efficient A removal devices13,14) would enhance blood A removal and increase A influx from the brain into the blood. Therefore, blood A changes and A removal efficiency were investigated in three hemodialysis patients undergoing blood purification with HexDC columns and PSf hemodialyzers (Hex-0103 in Table 1) as an observational study. These patients underwent blood purification with HexDC columns to remove blood 2 microglobulin for carpal tunnel syndrome and hemodialysis for renal failure. Figure 3D shows the clinical circuit. During hemodialysis, excess blood water was filtered out at approximately 10 mL/min. This filtration can be considered adsorptive filtration for A removal.

Figure 8A shows the plasma concentration changes for A140 and A142 in whole-body circulation. Both A140 and A142 decreased similarly. Figure 8B and C show the A removal efficiencies of the HexDC column and PSf hemodialyzer, respectively. A140 and A142 removal efficiencies for both devices were maintained during the 4 h treatment. The removal efficiencies were lower in this clinical setting than the removal efficiencies in the in vitro experiments (Figures 3A, 5A and C). The plasma flow rates were higher in human treatment (200 mL blood/min, approximately 130 mL plasma/min) than the flow rates in in vitro experiments (equivalent to 50 mL plasma/min in humans). Lower blood flow rates resulted in higher A removal efficiencies, as previously reported.14,17

Figure 8 A removal during hemodialysis with concomitant use of HexDC and PSf hemodialyzers for 4 h. (A) Changes in plasma A1-40 (left blue vertical axis) and A1-42 (right red vertical axis) concentrations in whole-body circulation. (B and C) A removal efficiencies of HexDC (B) or PSf hemodialyzers (C). (A1-40, blue solid line; A1-42, red dotted line).

Another method of enhancing A influx into the blood, an E-BARS with long-time treatment, was also believed to be effective. Blood A changes in hemodialysis patients using hemodialyzers alone for 4 h were already investigated in the previous study.15,16,18,19 We then hypothesized that longer hemodialysis times, such as 8 h (doubled compared with ordinal 4 h treatment), would enhance A influx into the blood. Three patients suffering from end-stage renal failure underwent overnight hemodialysis for 8 h using a PSf hemodialyzer alone (ON-13 in Table 1). Overnight hemodialysis during sleep for 8 h was provided because these patients worked during the day. This was also an observational study. Figure 3E shows the clinical circuit. The blood was partially filtered at a 69 mL/min rate during hemodialysis to remove excess water, resulting in enhanced A adsorption on the surface of small pores in the membrane wall (Figure 3B, adsorptive filtration).

Figure 9A shows the plasma concentration changes for A140 and A142 in whole-body circulation. Both A140 and A142 similarly decreased. The A removal efficiencies using the PSf hemodialyzer were maintained at over 60% during the 8 h treatment (Figure 9B). A concentrations in the filtrate of the dialyzers were also measured. The flow rate of the mixture of filtrate and waste dialysate was approximately 400 mL/min. The total volume was up to 192 L, and part of the fluid was collected at a rate of 1000 mL/h for the periods of 04 h and 48 h. Figure 9C shows the A concentrations in the filtrate and waste dialysate, indicating that almost all As were adsorbed (trapped) on the inner surface of the PSf-HFs.

Figure 9 A removal during hemodialysis with PSf hemodialyzer alone for 8 h. (A) Changes in plasma A1-40 (left blue vertical axis) and A1-42 (right red vertical axis) concentrations in whole-body circulation. (B) A removal efficiencies of the PSf hemodialyzer. (C) As concentrations in the filtrate from the PSf hemodialyzer. (A1-40, left blue vertical axis; A1-42, right red vertical axis; A1-40, blue solid line; A1-42, red dotted line).

Removing blood A evokes a large A influx into the blood,15,16,18,19,22 probably from the brain.20,22 A influx into the blood was estimated according to the equation shown in Figure 10 for studies of renal failure patients using the concomitant HexDC and PSf hemodialyzer for 4 h and using the hemodialyzer alone for 8 h (Figure 3D and E, respectively).

Figure 10 A influx into the blood was calculated by subtracting the A amounts decreased in the plasma from the A amounts removed by the devices.

Figure 11 shows A140 (Figure 11A) and A142 (Figure 11B) amounts removed by each device, and As decreased in the plasma compared with the starting amounts. The A amounts are shown separately for the 01, 14, and 04 h periods for both systems and 48 and 08 h for the dialyzer alone. A140 removed by HexDC increased time-dependently (blue diagonal cross lattice in Figure 11A). A140 removed by HexDC during the 14 h period (3 h) was nearly three times larger than the removal during the 01 h period. However, the A142 removed by HexDC and both A140 and A142 removed by PSf dialyzers showed no clear trend over time and were suppressed in later treatment periods.

Figure 11 A amounts removed by HexDC (blue diagonal cross lattice), by PSf hemodialyzer (orange solid bar), and A amounts decreased in the plasma (green vertical stripe) for each period. (A) A1-40, (B) A1-42.

Figure 12 shows the A influx evoked by the A removal systems, calculated based on the data shown in Figure 11. A140 influxes (blue diagonal striped bars in Figure 12) during concomitant use of the HexDC and PSf dialyzer were significantly (p < 0.05) higher than the influxes during use of the PSf dialyzer alone in the 14 h period. By contrast, A142 influxes (red solid bars in Figure 12) during concomitant use of HexDC and the PSf dialyzer were significantly (p < 0.05) lower than influxes during the use of the PSf dialyzer alone in the 01, 14, and 04 h periods. Consequently, the sums of A140 and A142 influxes (black horizontal striped bars in Figure 12) were not significantly different between the two systems.

Figure 12 A influx into the plasma evoked by concomitant use of HexDC and the PSf hemodialyzer (HexDC+Dialyzer) and by the PSf hemodialyzer alone (Dialyzer Only). A1-40, blue diagonal line (left black vertical axis); A1-42, red solid bar (right red vertical axis); summation of A1-40 and A1-42, black lateral stripe (left black vertical axis). (*p < 0.05).

The average A140 influx for both systems in the 14 h (3 h) period was nearly three times higher than the influx in the 01 h (1 h) period (11,549 ng vs 4042 ng for the concomitant use of HexDC and the PSf dialyzer and 8132 ng vs 3478 ng for PSf dialyzer alone). On the other hand, A142 influxes in both systems during the 14 h period were larger than those in the 01 h period, but not proportional to the treatment time (425 ng vs 256 ng for the concomitant use of HexDC and PSf dialyzer, and 892 ng vs 410 ng for PSf dialyzer-alone system).

A influxes for the PSf dialyzer alone during the 08 h period were not doubled compared with those in the 04 h period, as shown on the right of Figure 12. Thus, the influxes of both A140 and A142 may decrease over time during the treatment.

The absolute amounts of As removed, those decreased in systemic plasma, and A influxes are dependent on the beginning plasma A concentrations of each patient. Therefore, relative values for these A amounts were calculated relative to the plasma A amounts at the beginning of the treatment (Figure 13). Interestingly, standard deviations for each relative A value were far smaller than expected. Thus, the A amounts similarly changed for each patient during blood treatments.

Figure 13 Relative A amounts normalized to the A amounts existing in the plasma at the beginning of blood purification.(A and B) A1-40 (blue lines), (C and D) A1-42 (red lines). Relative A amount changes during treatment with concomitant use of HexDC and the PSf hemodialyzer (HexDC+Dialyzer) (A and C, pale green background). Relative A amount changes during treatment with PSf hemodialyzer alone (Dialyzer only) (B and D, light orange background). Solid lines with triangle symbols, relative A amounts removed by HexDC; dotted lines with cross square marks, relative A amounts removed by PSf hemodialyzer; dashed lines with circle symbols, relative A amounts decreased in the plasma.

Relative A amounts removed by HexDC and PSf dialyzers (solid lines and dotted lines in Figure 13, respectively) increased time-dependently. This suggests that HexDC and PSf dialyzers had adequate A adsorption capacity during the 4 and 8 h treatments. However, the changes were smaller in the latter half of the treatment than in the first half. The relative decreases in plasma A (dashed lines under 0% in Figure 13) seemed to plateau after 1 h of treatment. This indicates that blood A140 and A142 reached homeostasis, even though large amounts of A were removed from the blood because of A influx.

Figure 14 shows the comparison of relative A influx for the two A removal systems. As shown in Figure 14A, relative A140 influx after 4 h using the combined HexDC and PSf dialyzer was significantly higher than influx using the PSf dialyzer alone (p < 0.05). The total relative A140 influx for the PSf dialyzer alone at 8 h was similar to that of HexDC and PSf dialyzer at 4 h. In contrast to A140, relative A142 influx after 4 h using the HexDC and PSf dialyzer was slightly, but significantly, lower than that of the PSf dialyzer alone (Figure 14B). A total relative A1-42 influx during 8 h of treatment using the PSf dialyzer alone was almost double the A1-42 influx of the combined HexDC and PSf dialyzer during 4 h.

Figure 14 Relative A influxes normalized to the A amounts existing in the plasma at the beginning of blood purification. (A) Relative A1-40 influx into the plasma, (B) relative A1-42 influx into the plasma. Solid green lines with rhombus symbols, relative A influxes evoked by concomitant use of HexDC and the PSf hemodialyzer (HexDC+Dialyzer); dotted lines with square symbols, relative A influxes evoked by the PSf hemodialyzer alone (Dialyzer Only). *, p < 0.05.

Regarding A influx into the blood, we have reported that ordinal hemodialysis with hemodialyzers alone for 4 h evoked an influx of 7219 ng A140 and 664 ng A142 based on analysis of 30 hemodialysis patients.19 In this study, as shown in Figure 12, A140, A142, A140 + A142 influx evoked by the concomitant use of HexDC and the PSf hemodialyzer for 04 h were 15,591 5407 ng, 690 166 ng, and 16,281 5565 ng, respectively. Those by PSf hemodialyzer alone were 11,610 1335 ng, 1302 211 ng, and 12,912 1224 ng for 04 h, and 19,198 1556 ng, 1673 928 ng, and 20,871 1699 ng for 08 h, respectively. Thus, compared with E-BARS with hemodialyzers alone for 4 h, E-BARS with double devices of A removal (HexDC and PSf hemodialyzer) for 4 h evoked nearly doubled As (A140 + A142) influx: 7219 ng vs 16,281 ng, and E-BARS of longer treatment with PSf hemodialyzer alone for 8 h also evoked more than doubled or nearly tripled As (A140 + A142) influx: 7219 ng vs 20,871 ng. A influx in this study was two to three times larger than the estimated total As (7760 ng) in the normal human brain28 and far larger than As removed by peritoneal dialysis: 131.33 ng, which was approximately 2% of the total A in the normal brain.25 Therefore, efficient A removal systems, such as a combination of HexDC and PSf hemodialyzer or longer treatment time, may be more effective in removing brain As than ordinal hemodialysis (hemodialyzers alone) for 4 h.

One aim of our blood A removal systems was to enhance A influx (migration) from the brain into the blood, especially A142, which readily forms neurotoxic A142 oligomers. Both A removal systems in this study showed very similar time dependency (Figure 14B) for relative A142 influxes. However, PSf dialyzer alone evoked slightly higher (p < 0.05) relative A142 influx than the combined system of HexDC and PSf dialyzer. Furthermore, the 8 h treatment with the PSf hemodialyzer alone evoked significantly larger, almost doubled, A142 influx than the concomitant use of HexDC and the PSf hemodialyzer for 4 h (Figure 14B). Focused on A142 removal, PSf hemodialyzer alone may have enough ability to evoke A142 influx into the blood.

In contrast to the A142 influx, concomitant use of HexDC and the PSf hemodialyzer evoked a larger A140 influx (significantly for only 14 h) than the PSf hemodialyzer alone (Figures 12 and 14A).

Overall, A removal systems with concomitant use of HexDC and PSf hemodialyzer evoked similar or less A142 influxes and larger A140 influx compared with A influx using the PSf hemodialyzer alone. Although the reason for this difference is unclear at present, it provides information to establish appropriate systems of E-BARS.

Regarding discrepancy between this and previous studies, A influx with PSf hemodialyzer in 04 h period at night in this study was larger than those we reported previously for ordinal hemodialysis patients for 4 h during the day:19 12,912 ng vs 16,281 ng. One possible reason is the variations in hemodialyzer materials used. Hemodialyzer material in this study was only PSf, one of the efficient A adsorbents. By contrast, some hemodialyzers used in the previous study included less efficient A removal devices, such as cellulose triacetate. Another reason may be that blood purification was conducted overnight or daytime. In this study, the blood purification with the PSf hemodialyzer alone for 8 h was provided overnight, including when patients were sleeping, whereas 4 h blood purification was provided during the day in the previous study.19 It was reported that A concentrations in CSF are higher in the evening (about 18:0022:00) than during the awake daytime hours and decrease while a patient is sleeping (about 22:007:00).29,30 Therefore, the differences in As concentrations in CSF depending on the time of day might affect this studys results. Thus, blood A removal during sleeping might be an effective method for brain A removal.

The amounts of A140 and A142 removed by the PSf hemodialyzers in concomitant use with HexDC were smaller than the A amounts removed by PSf hemodialyzers alone in each period of 01, 14, and 04 h, as shown in Figure 11A and B (the solid orange bars of HexDC + Dialyzer and Dialyzer only). One explanation is that the A concentrations at the PSf hemodialyzer inlet (Figure 3D) were lower than the A concentrations for the PSf hemodialyzer directly connected with the blood vessels of patients (Figure 3E) because approximately 5060% of the As in the blood were already removed by the HexDC column (Figure 3D) before PSf hemodialyzer in the system of concomitant use of tandemly connected HexDC and PSf hemodialyzer. To use the total A removal activity capacity of PSf hemodialyzer, blood should be introduced in parallel to the HexDC and PSf hemodialyzer systems. However, such parallel systems require doubled blood flow rates, which are unsuitable for Japanese hemodialysis patients because of blood outflow limitations.

Figure 15 summarizes the factors that may affect blood A removal. The key factors are not only A removal efficacy of the device but also the treatment period, blood flow rates into the devices, A concentrations in the blood, A concentrations in CSF that change depending on the time of day and A production/degradation rates in the brain, the activity of A transporters (for example, LRP-1 and RAGE), and frequency of treatment (for example, three times a week, or once a month?) of A removal. When comparing dual A removal devices with a single A removal device, the relative A142 influx was similar (Figure 14B). Therefore, the rate of A influx to the blood from the brain, especially A142, might be the rate-limiting step for brain A142 removal, even if more effective devices are used for A removal.

Figure 15 A transportation pathway from the brain to A removal devices. Key factors affecting A influxes and removal are also shown.

As blood A removal devices, PSf hemodialyzer in adsorptive filtration methods and HexDC showed comparable adsorption capacity for plasma As. Doubled A removal devices consisting of tandemly connected HexDC and PSf hemodialyzer for 4 h evoked a larger A140 influx into the blood than PSf hemodialyzer alone for the same period. However, both systems evoked similar A142 influx for 4 h. These systems evoked As (A140 + A142) influx nearly two times larger than As existing in the normal brain. Furthermore, longer A removal evoked more influxes of A140 and A142. These findings of blood A removal systems may lead to an optimal clinical setting for therapy and prevention of AD.

The authors thank Hiroshi Tomizawa of Mizuno Clinic, and, Yuri Sakakibara, Kota Watanabe, Miki Kamiya, and Tatsuya Hama of Fujita Health University for their technical assistance. The authors also thank Yoshiyuki Hiki for fruitful discussion, and Fumiyasu Hirai and Ai Yonezawa of Kaneka for providing HexDC for in vitro experiments. This work was partly supported by KAKENHI (20509008, 23500531, 26282126) and the Smoking Research Foundation.

Nobuya Kitaguchi has stock ownership in Asahi Kasei Corporation Co., Ltd and reports grants from Japanese Government, grants from Smoking Research Foundation, grants from Asahi Kasei Medical Co. LTD, grants, non-financial support from Kaneka Corporation, during the conduct of the study.

The other authors declare that they have no conflict of interest.

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16. Kato M, Kawaguchi K, Nakai S, et al. Potential therapeutic system for Alzheimers disease: removal of blood As by hemodialyzers and its effect on the cognitive functions of renal-failure patients. J Neural Transm (Vienna). 2012;119:15331544. doi:10.1007/s00702-012-0844-5

17. Kitaguchi N, Kawaguchi K, Yamazaki K, et al. Adsorptive filtration systems for effective removal of blood amyloid : a potential therapy for Alzheimers disease. J Artif Organs. 2018;21:220229. doi:10.1007/s10047-017-1012-3

18. Kitaguchi N, Hasegawa M, Ito S, et al. A prospective study on blood A levels and the cognitive function of patients with hemodialysis: a potential therapeutic strategy for Alzheimers disease. J Neural Transm (Vienna). 2015;122:15931607. doi:10.1007/s00702-015-1431-3

19. Kitaguchi N, Tatebe H, Sakai K, et al. Influx of tau and amyloid- proteins into the blood during hemodialysis as a therapeutic extracorporeal blood A removal system for Alzheimers disease. J Alzheimers Dis. 2019;69:687707. doi:10.3233/JAD-190087

20. Sakai K, Senda T, Hata R, et al. Patients that have undergone hemodialysis exhibit lower amyloid deposition in the brain: evidence supporting a therapeutic strategy for Alzheimers disease by removal of blood amyloid. J Alzheimers Dis. 2016;51:9971002. doi:10.3233/JAD-151139

21. Kitaguchi N, Kato T, Matsunaga S, et al. Removal of blood amyloid- with hemodialysis reduced brain amyloid-, confirmed by brain imaging: a case report. Neuropsychiatr Dis Treat. 2018;14:29312937. doi:10.2147/NDT.S186118

22. Kitaguchi N, Kawaguchi K, Kinomura J, et al. [P2-042]: extracorporeal blood A removal system (EBARS) reduced soluble A in the brain by triggering influx into the blood: rat studies. Alzheimers Dement. 2017;13:P620P621. doi:10.1016/j.jalz.2017.06.690

23. Nakai S, Wakai K, Kanda E, et al. Is hemodialysis itself a risk factor for dementia? An analysis of nationwide registry data of patients on maintenance hemodialysis in Japan. Ren Replace Ther. 2018:4. doi:10.1186/s41100-018-0154-y.

24. Saito Y, Sakata M, Kobayakawa M, et al. Removal of A oligomers from the blood: a potential therapeutic system for Alzheimers disease. Neuropsychiatr Dis Treat. 2020;16:607627. doi:10.2147/NDT.S241074

25. Jin WS, Shen LL, Bu XL, et al. Peritoneal dialysis reduces amyloid-beta plasma levels in humans and attenuates Alzheimer-associated phenotypes in an APP/PS1 mouse model. Acta Neuropathol. 2017;134:207220. doi:10.1007/s00401-017-1721-y

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High cost of Biogen’s Alzheimer’s drug blocks getting reimbursement in US – Korea Biomedical Review

Posted: at 1:54 am


Experts from the Institute for Clinical and Economic Review (ICER), a U.S. non-profit organization, say Biogen's Alzheimer's disease treatment, Aduhelm (ingredient: aducanumab), is not cost-effective, putting a brake on its advance to the U.S. market.

At a meeting last Thursday, the ICER experts reviewed the cost and clinical trial results of Aduhelm set by Biogen. All 15 participants unanimously voted that Aduhelm does not provide more benefits to patients, doctors, and society than the current standard treatment.

The experts pointed out that while one of the later clinical trials submitted for approval showed that Aduhelm had some benefit in slowing disease progression, a different study contradicted such results. The expert group also took issue with the frequent reports of adverse events concerning amyloid-related imaging abnormalities (ARIA).

Biogen recently set the annual treatment cost of Aduhelm at $56,000 after the U.S. Food and Drug Administration (FDA) approved the treatment. However, the treatment cost does not include the price of a positron emission tomography (PET) scan or magnetic resonance imaging (MRI) for diagnosing Alzheimer's disease. Including these collateral costs, the figure soars up to about $100,000 a year.

"The price of Aduhelm set by Biogen does not reasonably match the clinical benefit," the ICER said in late June, pointing out that Biogen needs to lower the drug price by 85-95 percent from the current list price to meet a reasonable price tag.

At that time, ICER's estimated that the cost-effectiveness of Aduhelm ranges from a minimum of $3,000 to a maximum of $8,400, which is far lower than the price set by Biogen.

In response, Biogen's Chief Medical Officer Maha Radhakrishnan criticized the ICER, saying that evaluating drugs requires innovative thinking and a new framework for assessing potential value.

"We regret that ICER assessment missed this point," Radhakrishnan said.

However, ICER reconvened the experts meeting and presented opinions that the price set by Biogen for Aduhelm does not provide any benefits compared to existing treatments, which will likely have negative effects on the discussion of Medicare application to the drug that starts next week, industry insiders predicted.

Medicare is a health insurance system for the elderly in the United States. The federal government subsidizes 50 percent of medical expenses for seniors 65 years of age or older and people with disabilities who have paid social security tax for 20 years or more.

Currently, some major hospitals are refusing to prescribe Aduhelm until the drug receives coverage by Medicare, and private insurance companies are also delaying coverage plans.

Meanwhile, the FDA significantly reduced the number of treatment targets by inserting and updating the label for Aduhelm and restricted the drug use for "patients with mild cognitive impairment or mild dementia stage of the disease" on July 8.

In the updated label, the FDA added that Aduhelm treatment should only treat patients with mild cognitive impairment or mild dementia, as Biogen's trial only used the therapy in such patients, and that there are no safety or efficacy data for use at earlier or later stages than those studied.

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High cost of Biogen's Alzheimer's drug blocks getting reimbursement in US - Korea Biomedical Review

Alzheimer’s Association Welcomes CMS Announcement of National Coverage Determination Analysis on Treatment for Alzheimer’s Disease – Newswise

Posted: at 1:54 am


Newswise CHICAGO, July 12, 2021 /PRNewswire/ -- On behalf of all those living with Alzheimer's disease, their caregivers, and their families, we appreciate the Centers for Medicare & Medicaid Services (CMS) thoughtful consideration on coverage considerations for monoclonal antibodies targeting amyloid for the treatment of Alzheimer's disease, including aducanumab, which was recently approved by the Food and Drug Administration (FDA).

We welcome today's announcement of a National Coverage Determination (NCD) analysis, consistent with the Alzheimer's Associationposition. An NCD would help prevent regional and community level disparities due to barriers that would be difficult to overcome, particularly by those who have greater challenges accessing health care services.

As the leading voluntary health organization in Alzheimer's care, support and research, the Alzheimer's Association looks forward to providing comment as part of the NCD process. In addition, the Alzheimer's Association supports an NCD outcome that includes Coverage with Evidence Development (CED) to ensure confirmatory data is collected in a timeframe and manner that meaningfully informs important near term decision making by policymakers, payers, health care providers, and patients and their families.

As the only patient advocacy group with experience in leading neurology CED programs, the Association believes a well constructed CED study would create rapid, open access to crucial information regarding efficacy, safety and equity to help ensure that everyone who might benefit has access.

We're committed to working with CMS and with the private payer community to ensure coverage for those who would benefit from this treatment. Additionally, we call on CMS to provide immediate guidance to help our community navigate access to coverage as the NCD process moves forward over the next several months. Patients and their families are understandably eager for treatment to begin now; providers need to understand what will be covered as we wait for an eventual NCD.

The Alzheimer's Association position remains, coverage should include the appropriate population as represented by those studied in the clinical trials people with mild cognitive impairment (MCI) due to Alzheimer's or early stage Alzheimer's dementia.

If you or a loved one is experiencing memory changes, the Alzheimer's Association strongly encourages speaking with a health care provider for a thorough evaluation, diagnosis and to discuss treatment options. For more information on diagnosis or to find a local health care provider, visit the Alzheimer's Association atalz.org, or the Helpline 24/7 at 800.272.3900.

Alzheimer's AssociationThe Alzheimer's Association leads the way to end Alzheimer's and all other dementia by accelerating global research, driving risk reduction and early detection, and maximizing quality care and support. Our vision is a world without Alzheimer's and all other dementia. Visitalz.orgor call the 24/7 Helpline at 800.272.3900.

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Alzheimer's Association Welcomes CMS Announcement of National Coverage Determination Analysis on Treatment for Alzheimer's Disease - Newswise

Lilly and Banner Alzheimer’s Institute collaborate on planned Phase 3 prevention trial of donanemab – PRNewswire

Posted: at 1:54 am


INDIANAPOLIS and PHOENIX, July 15, 2021 /PRNewswire/ --Eli Lilly and Company (NYSE: LLY) and Banner Alzheimer's Institute today announced a strategic research collaboration as part of the planned Phase 3, randomized, placebo-controlled study evaluating donanemab in participants at risk for cognitive and functional decline related to Alzheimer's disease (TRAILBLAZER-ALZ 3). TRAILBLAZER-ALZ 3 will evaluate whether treatment with donanemab can slow the clinical progression of Alzheimer'sdisease in trial participants.

As part of the collaboration, Banner will leverage its expertise and proven leadership in Alzheimer's prevention trials, and support enrollment of trial participants with and without the e4 type of the apolipoprotein E (APOE4) gene through the Alzheimer's Prevention Registry's GeneMatchprogram. The collaboration will introduce a more virtual approach to the evaluation of Alzheimer's prevention therapies. Lilly and Banner are committed to using the screening and treatment data as a shared scientific resource. Lilly remains the sole sponsor of the clinical trial and plans to begin enrollment later this year.

"This collaboration combines Lilly's more than 30 years of dedication to Alzheimer's research with Banner's unique expertise and showcases our collective commitment to partner within the health care community to find potential treatments to end this devastating disease," said Mark Mintun, M.D., vice president of pain and neurodegeneration, Lilly. "Our TRAILBLAZER-ALZ 3 trial will evaluate whether donanemab can prevent clinical progression in patients who have evidence of Alzheimer's pathology, but don't yet demonstrate clinical symptoms. While these types of trials are challenging to enroll and conduct, Lilly, together with Banner, is proud to undertake the opportunity to bring about this new study in an area of high unmet medical need."

"We are excited about the chance to work with Lilly in the effort to find an effective Alzheimer's prevention therapy as soon as possible, introduce novel ways to increase the size, speed, and ease of participating in Alzheimer's prevention trials, and do so in ways that might benefit the entire field," said Eric M. Reiman, MD, Banner Alzheimer's Institute executive director and one of the study's lead principal investigators. "We must do everything we can to find and support the availability of effective prevention therapies for this devastating disease, and this trial includes several potentially transformational elements to help in this endeavor."

Donanemab is an investigational antibody that targets a modified form of beta amyloid called N3pG. Results from a Phase 2 study of donanemab were announced earlier this year. VisitLillyMemoryTrials.comfor additional information onenrolling in Alzheimer's disease trials.Donanemab is also being studied in the ongoing Phase 3 TRAILBLAZER-ALZ 2 study in early, symptomatic Alzheimer's disease patients. To learn more about the TRAILBLAZER-ALZ 2 study or to see prequalifications, visit http://www.trailblazer2study.com.

About Alzheimer's DiseaseAlzheimer's disease is a fatal illness that causes progressive decline in memory and other aspects of cognition. Dementia due to Alzheimer's disease is the most common form of dementia, accounting for 60 to 80 percent of all cases1. There are currently over 50 million people living with dementia around the world, with numbers expected to increase to nearly 152 million by 20502. Almost 10 million new cases of dementia are diagnosed each year worldwide, implying one new case every 3 seconds, and a significant increase in the caregiving burden placed on society and families.In the US alone, there was an increase of 8 million new caregivers from 2015 to 20203. The current annual societal and economic cost of dementia is estimated at $1 trillion, an amount that is expected to double by 2030 unless we find a way to slow the disease2.

In an addition to age and family history of AD, the greatest risk factor for developing AD is the presence of the apolipoprotein E 4 (APOE4) allele.1 Having one APOE4 allele increases the risk of developing Alzheimer's disease by approximately three times compared with those with two copies of the APOE3 form. Those who inherit two copies of the APOE4 allele have an 8 - 12-fold risk. In addition, those with the APOE4 allele are more likely to have beta-amyloid accumulation and Alzheimer's dementia at a younger age than those with the APOE2 or APOE3 forms of the APOE gene.

About Banner Alzheimer's InstituteSince its inception in 2006, Banner Alzheimer's Institute (BAI) has sought to find effective Alzheimer's disease prevention therapies without losing another generation, establish a new model of dementia care for patients and family caregivers, and forge new models of collaboration in biomedical research. It has made groundbreaking contributions to the unusually early detection, tracking, diagnosis and study of Alzheimer's, and aims to find an effective prevention therapy by 2025. It includes the pioneering Alzheimer's Prevention Initiative (API), an extensive profile of research studies and clinical trials, comprehensive clinical, family and community service programs, a leading brain imaging research program, and strategic partnerships with numerous public and private research organizations around the world. Learn more at http://www.BannerAlz.org.

About Alzheimer's Prevention InitiativeThe Alzheimer's Prevention Initiative (API) is an international collaborative formed to launch a new era of Alzheimer's prevention research. Led by the Banner Alzheimer's Institute, the API conducts prevention trials in cognitively healthy people at increased genetic risk for Alzheimer's disease. It will continue to establish the brain imaging, biological and cognitive measurements needed to rapidly test promising prevention therapies and provide registries to support enrollment into Alzheimer's-focused studies. API is intended to provide the scientific means, accelerated approval pathway and enrollment resources needed to evaluate the range of promising Alzheimer's prevention therapies and find ones that work without losing another generation. For more information, visit http://www.alzheimerspreventioninitiative.com.

AboutEli Lilly and CompanyLilly is a global healthcare leader that unites caring with discovery to make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit us at lilly.comand lilly.com/newsroom. P-LLY

Lilly Cautionary Statement Regarding Forward-Looking Statements

This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about donanemab as a potential treatment for people with Alzheimer's disease, the timing for Lilly's trials, and the benefits of a collaboration with Banner Alzheimer's Institute and reflects Lilly's current beliefs and expectations. However, as with any such undertaking, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that future study results will be consistent with study results to date, that donanemab will prove to be a safe and effective treatment for Alzheimer's disease, that donanemab will receive regulatory approval, that Lilly will realize the expected benefits of the collaboration, or that Lilly will execute its strategy as expected. For further discussion of these and other risks and uncertainties, see Lilly's Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.

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http://www.lilly.com

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Lilly and Banner Alzheimer's Institute collaborate on planned Phase 3 prevention trial of donanemab - PRNewswire

Early signs of Alzheimer’s can show up in your driving – New Haven Register

Posted: at 1:54 am


According to a study, there are certain qualities that make it possible to distinguish the early stages of the disease.

Entrepreneur en Espaol,Entrepreneur.com

July 16, 2021Updated: July 16, 2021 2:07p.m.

A study led by researcher Sayed Bayat suggests that certain forms of driving may be related to the early stages of Alzheimer's disease. To test this theory, an experiment was conducted involving 139 people over 65 years of age in Washington, United States.

As the BBC reports, with medical tests (analysis of the cerebrospinal fluid and positron emission tomography) it was diagnosed that half of the participants were in an early phase of progressive disease and the other half were not. With this in mind, the driving analysis was started for one year, each car was fitted with a locating device based on the Global Positioning System to record the movements and times in detail.

The differences they identified were that preclinical Alzheimer's patients tended to log fewer miles, drive slower, travel less at night, limit routes, visit fewer destinations, and make abrupt changes. "The way people move in their everyday environment, from the places they visit to the way they drive, can tell us a lot about their health," said Sayed Bayat.

Thanks to the data collection, it was possible to design a first model that predicts the probability of having preclinical Alzheimer's only using age and driving data, it was 86% accurate. But adding the results of an apolipoprotein E (APOE) genotype genetic test resulted in a 90% accuracy. It must always be remembered that only a small percentage of people end up developing Alzheimer's when it is due to genetic inheritance.

It must always be remembered that only a small percentage of people end up developing Alzheimer's when it is due to genetic inheritance / Image: Depositphotos.com

This new model could avoid expensive and invasive medical procedures to diagnose preclinical Alzheimer's, even though it takes longer than normal. The National Institute on Aging of the United States mentions that family members may notice that their loved one takes longer to complete an easy trip, that he or she drives more erratically or gets confused on the pedal.

This article originally appeared on entrepreneur.com

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Early signs of Alzheimer's can show up in your driving - New Haven Register

Helping families deal with another pandemic: Alzheimer’s disease – Morning Journal News

Posted: June 6, 2021 at 1:50 am


By CATHY BROWNFIELD

Family Recovery Center publicist

Mr. Bidens recent remarks about Alzheimers has gained public attention. Conspiracy theorists have jumped on it. But the concept is not a new one. The need for answers was as great 20, 30 years ago or longer. We know more now, but there is still so much that we dont know.

Mom has been gone for nearly 10 years. It is when you are looking back that you see the red flags and question how you could have missed them. The answer: The signs are subtle. And you dont realize you should be looking for them.

My mother said she came out of work and found her car. But her surroundings did not look familiar to her. She wasnt sure how to get home from that parking lot.

So, how did you find your way home? I asked.

I followed all the other cars until I got where I recognized things, she answered.

Dad called me on the phone. Your mother went to Alliance by herself. Im worried she might get lost.

My mother knew her way around. She was the navigator when our family traveled in the truck and camper, the map reader. Shed gotten us well into Canadas Algonquin Park and back again. She had gotten us to so many destinations and back home again. How could she get lost between home and Salem or Alliance or anywhere else in Columbiana County?

The Alzheimers Association reports that more than 6 million Americans age 65 and older are living with Alzheimers right now. The disease kills more people than breast cancer and prostate cancer combined. In fact, deaths from other chronic conditions like heart disease, diabetes and kidney disease, have declined while the number of deaths attributed to Alzheimers has increased 145 percent! One in three seniors dies with Alzheimers or other dementias.

People with Alzheimers or other dementias have twice as any hospital stays as other older people. They have more skilled nursing facility stays and home health care visits per year than other people and are more likely to receive adult day care services and nursing home care, says Alzheimers Association.

Ohio statistics show that the number of people with Alzheimers in the state for 2020 is 220,000. By 2025 it is expected to be 250,000. There are 442,000 caregivers providing 590,000,000 hours of unpaid care.

The Alzheimers Association says that, On average, people age 65 and older survive four to eight years after diagnosis yet some live as long as 20 years with Alzheimers

One in three caregivers is age 65 or older. Most are women, specifically daughters. Many of them are the sandwich generation, caring for elderly parents and children under age 18. There are many challenges for caregivers.

Black Americans are twice as likely to have Alzheimers as older White Americans, but more than half believe that future care will not be equally shared. Older Hispanics are one and a half times as likely as White Americans to have dementia, but many of them do not believe they will live long enough to develop dementia.

The disease is an emotional wrecking ball, awful for the person who has it, but perhaps worse for those who provide the care for them and watch the decline of their loved one. You learn to lie to them, I was once advised. I couldnt lie to my mother, but I did learn ways to word things that she accepted easily. (Well, I am a wordsmith.) The disease is difficult for families to navigate. When you add in trauma from other family issues, it becomes easy to be overwhelmed. You will get to the other side of things eventually, but in the meantime the struggle is real. And there are people who can help you find ways to cope.

Family Recovery Center helps families to find ways to navigate through the challenges we face. For more information about the agencys treatment and education programs, contact FRC at 964 N. Market St., Lisbon; phone, 330-424-1468, or email, info@familyrecovery.org. FRC is funded in part by the Columbiana County Mental Health and Recovery Services Board.

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