Likely cause of Alzheimer’s identified in new study

The Centers for Disease Control and Prevention (CDC) estimate that up to 5.8 million peopleTrusted Source in the United States live with Alzheimer’s disease.

Alzheimer’s disease is a neurodegenerative condition affecting parts of the brain associated with memory, thought, and language. Its symptoms range from mild memory loss to the inability to hold conversations to environmental disorientation and mood changes.

Previous research has suggested that various factors — such as age, family history, diet, and environmental factors — combine to influence a person’s risk of Alzheimer’s disease.

However, scientists in Australia have recently discovered an additional factor that may be responsible for the development of this neurodegenerative condition.

Lead study author Dr. John Mamo, Ph.D. — distinguished professor and director of the Curtin Health Innovation Research Institute at Curtin University in Perth, Australia — explained to Medical News Today the conclusion from the new research.

He said, “To find new opportunities to prevent and treat Alzheimer’s, we need to understand what actually causes the disease, and presently that is not established.”

“This study,” he added, “shows that exaggerated abundance in blood of potentially toxic fat-protein complexes can damage microscopic brain blood vessels called capillaries and, thereafter, leak into the brain, causing inflammation and brain cell death.”

“[Changes] in dietary behaviors and certain medications could potentially reduce blood concentration of these toxic fat-protein complexes, [subsequently] reducing the risk for Alzheimer’s or [slowing] down the disease progression,” he concluded.

The findings appear in the journal PLOS Biology.

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What the results say

The researchers found that when the amyloid-beta proteins made in the liver of the test mice combined with fats and traveled to the brain, they interfered with the proper functioning of the brain’s microscopic blood vessels, or capillaries.

This dysfunction in the blood-brain barrier led to the protein-fat complexes leaking from the blood into the brain, resulting in inflammation. This inflammation occurred in both the test group and the control group, but it started at a much younger age in the test group.

Unlike in the control group, this inflammation was also associated with marked degeneration in the brain cells of the mice in the test group when examined under a microscope. The scientists only rarely saw this neurodegeneration in the control mice, and it was usually at a much older age.

The team also assessed a marker of neurodegeneration and found it to be approximately two times greater in the test mice than in control mice of the same age.

So, it was unsurprising that during the test for cognitive function, the test mice performed approximately half as well as the control group at retention of learning.

These findings suggest explanations to long standing questions about the role of amyloid-beta in Alzheimer’s disease development.

Warren Harding, board chairman of Alzheimer’s WA, revealed to MNT the significance of the study results. He said:

Article culled from MedicalNewsToday

NIH unveils new online tool to improve Alzheimer’s clinical trials recruitment

The National Institute on Aging (NIA), part of the National Institutes of Health, has launched a new online research tool to help increase participation by traditionally underrepresented populations in clinical trials(link is external) on Alzheimer’s disease and related dementias. Unveiled at the Alzheimer’s Association International Conference (AAIC), Outreach Pro enables those involved with leading clinical research to create and customize participant recruitment communications such as websites, handouts, videos, and social media posts.

“We are facing a critical and growing need for people living with Alzheimer’s and related dementia, as well as those at higher risk, and healthy people, to participate in clinical trials,” said NIA Director, Richard J. Hodes M.D. “That need is especially acute for frequently underrepresented groups such as Black and Hispanic Americans, which is why Outreach Pro includes an emphasis on helping clinical trial researchers connect with these and other important communities.”

Outreach Pro is an integral part of NIA’s efforts to implement the National Strategy for Recruitment and Participation in Alzheimer’s and Related Dementias Clinical Research. Released in 2018, the national strategy was developed in collaboration with the Alzheimer’s Association with input from government, private sector, academic, and industry stakeholders, as well as from individuals, caregivers, and study participants. The overarching goal is to engage broader segments of the public, including underrepresented populations, to participate in Alzheimer’s and related dementias clinical research.

“It is critical that clinical trials have appropriate representation to ensure we have a complete understanding of how well different therapies or approaches to dementia care work in different populations,” said Holly Massett, Ph.D., NIA senior advisor on clinical research recruitment and engagement, who oversees the implementation of the national strategy. “Outreach Pro was designed to provide well-tested and culturally appropriate outreach materials that resonate with diverse populations and encourage them to participate in clinical trials.”

To use Outreach Pro, researchers and clinicians first select desired templates with one of three communication goals in mind: 1) to educate about Alzheimer’s, related dementias, and/or brain health; 2) to increase awareness and interest in Alzheimer’s and related dementias clinical trials; or, 3) to provide information about a specific Alzheimer’s or related dementia clinical trial currently enrolling participants. Each template can then be tailored using a central library of messages, headlines, photos, and text that have been extensively tested among individuals representing diverse and underserved populations.

Outreach Pro’s current library of content includes materials specifically designed for a range of audiences, including Black Americans and Hispanic/Latinos. Initially, the materials will be available in English and Spanish, and there are plans underway to add Asian American and Pacific Islander resources and languages by Fall 2021. Materials for American Indian and Alaska Native communities will be developed and added in 2022.

NIA developed Outreach Pro and its content systematically by using literature reviews, environmental scans, listening sessions with stakeholders, focus groups, national surveys, and user testing. The NIA team created tool features in a culturally responsive way, so that all stages of content development reflect the culture and languages of the communities for whom the materials are designed. NIA plans to add content and scale up the tool’s capabilities based on feedback and performance measurement.

Outreach Pro expands NIA’s resources dedicated to recruitment diversity. For example, in 2020, NIA funded four exploratory Alzheimer’s Disease Research Centers that will broaden research initiatives with underrepresented groups, including Black Americans, Native Americans, and those in rural communities. In 2019, NIA launched the Alzheimer’s and Dementia Outreach, Recruitment, and Engagement (ADORE) Resources. The ADORE repository offers the research community resources to support recruitment and retention of volunteers into clinical trials and studies.

NIH invests in next iteration of public-private partnership to advance precision medicine research for Alzheimer’s disease

The National Institutes of Health has launched the next version of the Accelerating Medicines Partnership (AMP) Alzheimer’s disease program (AMP AD 2.0) to expand the open science, big data approach for identifying biological targets for therapeutic intervention.

AMP AD 2.0 is supporting new technologies, including cutting-edge, single-cell profiling and computational modeling, to enable a precision medicine approach to therapy development. Managed through the Foundation for the NIH (FNIH), AMP AD 2.0 brings together NIH, industry, non-profit and other organizations with a shared goal of using open science practices to accelerate the discovery of new drug targets, biomarkers and disease subtypes.

“Unraveling the complex biological mechanisms that cause Alzheimer’s disease is critical for therapeutic development,” said NIH Director Francis S. Collins, M.D., Ph.D. “AMP AD 2.0 aims to add greater precision to the molecular maps developed in the first iteration of this program. This will identify biological targets and biomarkers to inform new therapeutic interventions for specific disease subtypes.”

Alzheimer’s, the most common cause of dementia, affects an estimated 5.8 million Americans 65 and older. Because the prevalence of this disease is greater among Black and Latino Americans than among white Americans, AMP AD 2.0 will expand the molecular characterization of Alzheimer’s in brain, blood and spinal fluid samples collected in these diverse populations. These datasets will allow the AMP AD 2.0 research teams to refine the characterization of new targets, discover new fluid biomarkers, define disease subtypes and increase the understanding of causative factors and steps in disease progression. The knowledge gained will inform the development of therapies that can be tailored to different stages of the disease and diverse disease risk profiles.

“AMP AD has helped transform the way we learn about the disease process and identify new targets for treatment,” said Richard J. Hodes, M.D., director of the National Institute on Aging (NIA), part of NIH.  “By expanding the molecular characterization of Alzheimer’s  disease to be more inclusive of diverse populations and by renewing the commitment to open science practices for sharing data, methods and results, we will enable researchers across the globe to better understand the complex nature of the disease and take a precision medicine approach to the development of effective treatments.”

Genetic study of Lewy body dementia supports ties to Alzheimer’s and Parkinson’s diseases

In a study led by National Institutes of Health researchers, scientists found that five genes may play a critical role in determining whether a person will suffer from Lewy body dementia, a devastating disorder that riddles the brain with clumps of abnormal protein deposits called Lewy bodies. Lewy bodies are also a hallmark of Parkinson’s disease. The results, published in Nature Genetics, not only supported the disease’s ties to Parkinson’s disease but also suggested that people who have Lewy body dementia may share similar genetic profiles to those who have Alzheimer’s disease.

“Lewy body dementia is a devastating brain disorder for which we have no effective treatments. Patients often appear to suffer the worst of both Alzheimer’s and Parkinson’s diseases. Our results support the idea that this may be because Lewy body dementia is caused by a spectrum of problems that can be seen in both disorders,” said Sonja Scholz, M.D., Ph.D., investigator at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and the senior author of the study. “We hope that these results will act as a blueprint for understanding the disease and developing new treatments.”

The study was led by Dr. Scholz’s team and researchers in the lab of Bryan J. Traynor, M.D., Ph.D., senior investigator at the NIH’s National Institute on Aging (NIA).

Lewy body dementia usually affects people over 65 years old. Early signs of the disease include hallucinations, mood swings, and problems with thinking, movements, and sleep. Patients who initially have cognitive and behavioral problems are usually diagnosed as having dementia with Lewy bodies, but are sometimes mistakenly diagnosed with Alzheimer’s disease. Alternatively, many patients, that are initially diagnosed with Parkinson’s disease, may eventually have difficulties with thinking and mood caused by Lewy body dementia. In both cases, as the disease worsens, patients become severely disabled and may die within eight years of diagnosis.An NIH-led study found that the sequences of five genes may help determine whether a person will suffer from Lewy body dementia, a devastating brain disorder.Scholz lab, NIH/NINDS

A growing body of evidence suggests genetics may play a role in the disorder and that some cases may be inherited. Scientists have found that some of these rare cases can be caused by mutations in the gene for alpha-synuclein (SNCA), the main protein found in Lewy bodies. Further studies have found that variants in the gene for apolipoprotein E (APOE), which is known to play a role in Alzheimer’s disease, may also play one in Lewy body dementia.

“Compared to other neurodegenerative disorders, very little is known about the genetic forces behind Lewy body dementia,” said Dr. Traynor. “To get a better understanding we wanted to study the genetic architecture of Lewy body dementia.”

Combination of healthy lifestyle traits may substantially reduce Alzheimer’s

Combining more healthy lifestyle behaviors was associated with substantially lower risk for Alzheimer’s disease in a study that included data from nearly 3,000 research participants.

Combining four or five healthy lifestyle behaviors — such as swimming — may lower risk of Alzheimer’s disease.NIA

Those who adhered to four or all of the five specified healthy behaviors were found to have a 60% lower risk of Alzheimer’s. The behaviors were physical activity, not smoking, light-to-moderate alcohol consumption, a high-quality diet, and cognitive activities. Funded by the National Institute on Aging (NIA), part of the National Institutes of Health, this research was published in the June 17, 2020, online issue of Neurology, the medical journal of the American Academy of Neurology.

“This observational study provides more evidence on how a combination of modifiable behaviors may mitigate Alzheimer’s disease risk,” said NIA Director Richard J. Hodes, M.D. “The findings strengthen the association between healthy behaviors and lower risk, and add to the basis for controlled clinical trials to directly test the ability of interventions to slow or prevent development of Alzheimer’s disease.”

The research team reviewed data from two NIA-funded longitudinal study populations: The Chicago Health and Aging Project (CHAP)(link is external) and the Memory and Aging Project (MAP)(link is external). They selected participants from those studies who had data available on their diet, lifestyle factors, genetics, and clinical assessments for Alzheimer’s disease. The resulting data pool included 1,845 participants from CHAP and 920 from MAP.

The researchers scored each participant based on five healthy lifestyle factors, all of which have important health benefits:

• At least 150 minutes per week of moderate- to vigorous-intensity physical activity – Physical activity is an important part of healthy aging.
• Not smoking – Established research has confirmed that even in people 60 or older who have been smoking for decades, quitting will improve health.
• Light-to-moderate alcohol consumption – Limiting use of alcohol may help cognitive health.
• A high-quality, Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, which combines the Mediterranean diet and Dietary Approaches to Stop Hypertension (DASH) diet – The MIND diet focuses on plant-based foods linked to dementia prevention.
• Engagement in late-life cognitive activities – Being intellectually engaged by keeping the mind active may benefit the brain.

A 2017 research review and report commissioned by NIA also concluded that evidence on lifestyle factors such as increasing physical activity, along with blood pressure management and cognitive training, is “encouraging although inconclusive” for preventing Alzheimer’s. Since then, more research has emerged, such as the SPRINT MIND trial, which suggests intensive blood pressure control may slow age-related brain damage, and new trials have launched. 

High rates of dementia, Alzheimer’s observed among older people with Down syndrome

 

A study of Wisconsin Medicaid enrollees with Down syndrome has found that more than half of those ages 55 and older have filed at least three claims for dementia and nearly a third have filed at least three claims for Alzheimer’s disease.

The analysis was funded by the National Institutes of Health and the Agency for Health Care Research and Quality, and it appears in JAMA Neurology.

People with Down syndrome are at higher risk for dementia as they age. The study authors noted that nearly all adults with Down syndrome develop neurological changes by age 40, but symptoms may not appear for decades. The authors added that population studies are needed to identify when symptoms begin so that families and health care systems can plan care for people with Down syndrome as they age.

In the current study, researchers led by Eric Rubenstein, Ph.D., and colleagues at the University of Wisconsin-Madison analyzed claims records by 2,968 Wisconsin Medicaid enrollees with Down syndrome from 2008 to 2018. Among those ages 40 to 54, 18.8% (190 of 1013) had filed dementia claims. There was a 40% chance that a person with Down syndrome age 40 to 54 years old would file a dementia claim over the next 11 years; there was a 67% chance that a person with Down syndrome age 55 or older would file such a claim. Among men and women with Down syndrome younger than 40, the likelihood of dementia was roughly equal, but from ages 40 to 54, dementia was 23% more likely in women.

Because eligibility requirements for people with Down syndrome are similar among Medicaid programs, other states may likely have a comparable proportion of claims for dementia and Alzheimer’s disease in this population.

NIH funding for the study was provided by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences.

Guidelines proposed for newly defined Alzheimer’s-like brain disorder

A recently recognized brain disorder that mimics clinical features of Alzheimer’s disease has for the first time been defined with recommended diagnostic criteria and other guidelines for advancing and catalyzing future research.

Limbic-predominant Age-related TDP-43 Encephalopathy, or LATE, as seen by microscope and MRI. Nelson et. al. and Brain, DOI: 10.1093/brain/awz099.

Scientists from several National Institutes of Health-funded institutions, in collaboration with international peers, described the newly-named pathway to dementia, Limbic-predominant Age-related TDP-43 Encephalopathy, or LATE, in a report published on April 30, 2019, in the journal Brain.

“While we’ve certainly been making advances in Alzheimer’s disease research — such as new biomarker and genetic discoveries—we are still at times asking, ‘When is Alzheimer’s disease not Alzheimer’s disease in older adults?’” said Richard J. Hodes, M.D., director of the National Institute on Aging (NIA), part of the NIH. “The guidance provided in this report, including the definition of LATE, is a crucial step toward increasing awareness and advancing research for both this disease and Alzheimer’s as well.”

Alzheimer’s is the most common form of dementia, which is the loss of cognitive functions — thinking, remembering, and reasoning — and every-day behavioral abilities. In the past, Alzheimer’s and dementia were often considered to be the same. Now there is rising appreciation that a variety of diseases and disease processes contribute to dementia. Each of these diseases appear differently when a brain sample is examined at autopsy. However, it has been increasingly clear that in advanced age, a large number of people had symptoms of dementia without the telltale signs in their brain at autopsy. Emerging research seems to indicate that the protein TDP-43 — though not a stand-alone explanation — contributes to that phenomenon.

What is TDP-43?

TDP-43 (transactive response DNA binding protein of 43 kDa) is a protein that normally helps to regulate gene expression in the brain and other tissues. Prior studies found that unusually misfolded TDP-43 has a causative role in most cases of amyotrophic lateral sclerosis and frontotemporal lobar degeneration.  However, these are relatively uncommon diseases. A significant new development seen in recent research is that misfolded TDP-43 protein is very common in older adults. Roughly 25 percent of individuals over 85 years of age have enough misfolded TDP-43 protein to affect their memory and/or thinking abilities.

TDP-43 pathology is also commonly associated with hippocampal sclerosis, the severe shrinkage of the hippocampal region of the brain—the part of the brain that deals with learning and memory. Hippocampal sclerosis and its clinical symptoms of cognitive impairment can be very similar to the effects of Alzheimer’s.

“Recent research and clinical trials in Alzheimer’s disease have taught us two things: First, not all of the people we thought had Alzheimer’s have it; second, it is very important to understand the other contributors to dementia,” said Nina Silverberg, Ph.D., director of the Alzheimer’s Disease Centers Program at NIA. In the past many people who enrolled in clinical trials likely were not positive for amyloid. “Noting the trend in research implicating TDP-43 as a possible Alzheimer’s mimic, a group of experts convened a workshop to provide a starting point for further research that will advance our understanding of another contributor to late life brain changes,” Silverberg explained. In addition to U.S. scientists, experts included researchers from Australia, Austria, Sweden, Japan, and the United Kingdom with expertise in clinical diagnosis, neuropathology, genetics, neuropsychology and brain imaging.

Supported by NIA, the workshop was held Oct. 17 and 18, 2018, in Atlanta, and co-chaired by Dr. Silverberg and Peter Nelson, M.D., Ph.D., from the University of Kentucky, Lexington, the lead author on the paper. As published in the report, outcomes included classification guidelines for diagnosis and staging of LATE as well as recommendations for future research directions.

LATE: A new research priority

The authors wrote that LATE is an under-recognized condition with a very large impact on public health. They emphasized that the “oldest-old” are at greatest risk and importantly, they believe that the public health impact of LATE is at least as large as Alzheimer’s in this group.

The clinical and neurocognitive features of LATE affect multiple areas of cognition, ultimately impairing activities of daily life. Additionally, based on existing research, the authors suggested that LATE progresses more gradually than Alzheimer’s. However, LATE combined with Alzheimer’s—which is common for these two highly prevalent brain diseases—appears to cause a more rapid decline than either would alone.

“It is important to note that the disease itself is not new. LATE has been there all along, but we hope this report will enable more rapid advancement in research to help us better understand the causes and open new opportunities for treatment,” said Dr. Silverberg.