Memory loss reversed or abated in those with cognitive decline

July 31, 2020

Science Daily/IOS Press

Researchers sought to determine whether a comprehensive and personalized program, designed to mitigate risk factors of Alzheimer's disease could improve cognitive and metabolic function in individuals experiencing cognitive decline. Findings provided evidence that this approach can improve risk factor scores and stabilize cognitive function.

Latest research from Affirmativ Health succeeds in treating cognitive decline using personalized, precision medicine.

Affirmativ Health sought to determine whether a comprehensive and personalized program, designed to mitigate risk factors of Alzheimer's disease could improve cognitive and metabolic function in individuals experiencing cognitive decline. Findings provided evidence that this approach can improve risk factor scores and stabilize cognitive function.

July 31, 2020/Sonoma, CA Cognitive decline is a major concern of the aging population. Already, Alzheimer's disease affects approximately 5.4 million Americans and 30 million people globally. Without effective prevention and treatment, the prospects for the future are bleak. By 2050, it is estimated that 160 million people globally will have the disease, including 13 million Americans, leading to potential bankruptcy of the Medicare system. Unlike several other chronic illnesses, Alzheimer's disease is on the rise -- recent estimates suggest that Alzheimer's disease has become the third leading cause of death in the United States behind cardiovascular disease and cancer. Since its first description over 100 years ago, Alzheimer's disease has been without effective treatment. While researchers continue to seek out a cure, it is becoming clear that there are effective treatment options. More and more research supports the conclusion that Alzheimer's disease is not a disease of only Beta Amyloid plaques and Tao tangles but a complex and systemic disease. In this study of patients with varying levels of cognitive decline, it is demonstrated how a precision and personalized approach results in either stabilization or improvement in memory.

Interventions to stop the progression of Alzheimer's disease have been marginally successful at best. This study uses a more comprehensive, personalized approach addressing each participant's unique risk factors. "The findings, published in the Journal of Alzheimer's Disease Reports (Journal of Alzheimer's Disease Reports 4(1)), are encouraging and indicate that a more extensive clinical study is warranted," said Brian Kennedy, PhD, Director of The Centre for Healthy Aging, National University Health System, Singapore and Chief Scientific Officer, Affirmativ Health.

The Affirmativ Health scientific team, after thorough review of published research, has developed a comprehensive approach to addressing scientifically supported risk factors that have been rigorously defined as interventions to promote prevention, increased resiliency, and stabilization of brain function in the realm of AD and dementia. Utilizing cutting edge technology in concert with in-person coaching and consultation, we are demonstrating that a multi-modal and personalized approach promotes an improved resiliency and restoration of optimal brain function. The personalized therapeutic program includes genetics, an extensive blood panel, medical history and lifestyle data to evaluate relevant metabolic risk factors and nutrient levels associated with cognitive health. "Target laboratory levels differ from standard laboratory ranges as the goal is to reach optimized levels for cognitive health," Ginger Schechter, MD, Chief Medical Officer, Affirmativ Health

The study approach considers more than 35 factors known to contribute to cognitive decline. Results demonstrate that certain of those factors are more affected than others again demonstrating the need for a more precise treatment plan. "This study supports the need for an approach that focuses on a one-size fits one, not a one-size fits all, approach that comprehensively assesses all involved risk factors affecting memory loss," Denise M Kalos, CEO Affirmativ Health

In conjunction with the publication of this vital study, and to expose alternative treatment options for Alzheimer's disease and cognitive decline, the team at Affirmativ Health has written a book, Outsmart your Brain -- an Insider's Guide to Life-Long Memory. "Memory is not something that should diminish with age; you are never too young to start developing healthy habits that can ultimately impact your cognition," Outsmart Your Brain. This book leverages the foundation of Affirmativ Health's research to deliver a tips and tools guide for the maintenance of good cognitive health. "Far too few people understand how critical lifestyle and dietary choices are for brain function. 'Outsmart Your Brain' is an important tool to get this information into the hands of those who should know it, everyone!, in easy-to-understand language," Ryan R. Fortna, MD, PhD, Chief Medical/Scientific Officer, ADx Healthcare.

https://www.sciencedaily.com/releases/2020/07/200731104124.htm

Biochemists discover new insights into what may go awry in brains of Alzheimer's patients

August 19, 2019

Science Daily/University of California - Los Angeles

More than three decades of research on Alzheimer's disease have not produced any major treatment advances for those with the disorder, according to a UCLA expert who has studied the biochemistry of the brain and Alzheimer's for nearly 30 years. "Nothing has worked," said Steven Clarke, a distinguished professor of chemistry and biochemistry. "We're ready for new ideas." Now, Clarke and UCLA colleagues have reported new insights that may lead to progress in fighting the devastating disease.

Scientists have known for years that amyloid fibrils -- harmful, elongated, water-tight rope-like structures -- form in the brains of people with Alzheimer's, and likely hold important clues to the disease. UCLA Professor David Eisenberg and an international team of chemists and molecular biologists reported in the journal Nature in 2005 that amyloid fibrils contain proteins that interlock like the teeth of a zipper. The researchers also reported their hypothesis that this dry molecular zipper is in the fibrils that form in Alzheimer's disease, as well as in Parkinson's disease and two dozen other degenerative diseases. Their hypothesis has been supported by recent studies.

Alzheimer's disease, the most common cause of dementia among older adults, is an irreversible, progressive brain disorder that kills brain cells, gradually destroys memory and eventually affects thinking, behavior and the ability to carry out the daily tasks of life. More than 5.5 million Americans, most of whom are over 65, are thought to have dementia caused by Alzheimer's.

The UCLA team reports in the journal Nature Communications that the small protein beta amyloid, also known as a peptide, that plays an important role in Alzheimer's has a normal version that may be less harmful than previously thought and an age-damaged version that is more harmful.

Rebeccah Warmack, who was a UCLA graduate student at the time of the study and is its lead author, discovered that a specific version of age-modified beta amyloid contains a second molecular zipper not previously known to exist. Proteins live in water, but all the water gets pushed out as the fibril is sealed and zipped up. Warmack worked closely with UCLA graduate students David Boyer, Chih-Te Zee and Logan Richards; as well as senior research scientists Michael Sawaya and Duilio Cascio.

What goes wrong with beta amyloid, whose most common forms have 40 or 42 amino acids that are connected like a string of beads on a necklace?

The researchers report that with age, the 23rd amino acid can spontaneously form a kink, similar to one in a garden hose. This kinked form is known as isoAsp23. The normal version does not create the stronger second molecular zipper, but the kinked form does.

"Now we know a second water-free zipper can form, and is extremely difficult to pry apart," Warmack said. "We don't know how to break the zipper."

The normal form of beta amyloid has six water molecules that prevent the formation of a tight zipper, but the kink ejects these water molecules, allowing the zipper to form.

"Rebeccah has shown this kink leads to faster growth of the fibrils that have been linked to Alzheimer's disease," said Clarke, who has conducted research on biochemistry of the brain and Alzheimer's disease since 1990. "This second molecular zipper is double trouble. Once it's zipped, it's zipped, and once the formation of fibrils starts, it looks like you can't stop it. The kinked form initiates a dangerous cascade of events that we believe can result in Alzheimer's disease."

Why does beta amyloid's 23rd amino acid sometimes form this dangerous kink?

Clarke thinks the kinks in this amino acid form throughout our lives, but we have a protein repair enzyme that fixes them.

"As we get older, maybe the repair enzyme misses the repair once or twice," he said. "The repair enzyme might be 99.9% effective, but over 60 years or more, the kinks eventually build up. If not repaired or if degraded in time, the kink can spread to virtually every neuron and can do tremendous damage."

"The good news is that knowing what the problem is, we can think about ways to solve it," he added. "This kinked amino acid is where we want to look."

The research offers clues to pharmaceutical companies, which could develop ways to prevent formation of the kink or get the repair enzyme to work better; or by designing a cap that would prevent fibrils from growing.

Clarke said beta amyloid and a much larger protein tau -- with more than 750 amino acids -- make a devastating one-two punch that forms fibrils and spreads them to many neurons throughout the brain. All humans have both beta amyloid and tau. Researchers say it appears that beta amyloid produces fibrils that can lead to tau aggregates, which can spread the toxicity to other brain cells. However, exactly how beta amyloid and tau work together to kill neurons is not yet known.

In this study, Warmack produced crystals, both the normal and kinked types, in 15 of beta amyloid's amino acids. She used a modified type of cryo-electron microscopy to analyze the crystals. Cryo-electron microscopy, whose development won its creators the 2017 Nobel Prize in chemistry, enables scientists to see large biomolecules in extraordinary detail. Professor Tamir Gonen pioneered the modified microscopy, called microcrystal electron diffraction, which enables scientists to study biomolecules of any size.

https://www.sciencedaily.com/releases/2019/08/190819164346.htm

Amyloid is a less accurate marker for measuring severity, progression of Alzheimer's

August 6, 2019

Science Daily/University of Pennsylvania School of Medicine

Researchers find fluorodeoxyglucose (FDG) PET is a better indicator of cognitive performance when compared to PET scans that detect amyloid protein.

While the presence of beta-amyloid plaques in the brain may be a hallmark of Alzheimer's disease, giving patients an amyloid PET scan is not an effective method for measuring their cognitive function, according to a new study from researchers in the Perelman School of Medicine at the University of Pennsylvania and Thomas Jefferson University. The researchers concluded that fluorodeoxyglucose (FDG) PET, which measures the brain's glucose consumption as a marker of neural activity, is a stronger approach for assessing the progression and severity of Alzheimer's and mild cognitive impairment (MCI) as compared to florbetapir-PET scans, which reveal amyloid protein deposits in the brain. This suggests that FDG-PET is also a better means for determining the effectiveness of Alzheimer's therapies, as well as tracking patients' disease advancement, in both clinical and research settings. Results of this study are detailed in the August issue of the Journal of Alzheimer's Disease.

"Both florbetapir-PET and FDG-PET are approved diagnostic methods for Alzheimer's disease, and both appear to be effective in indicating some sort of cognitive impairment. However, we have now shown that FDG-PET is significantly more precise in clinical studies, and it is also available for routine use with modest costs," said the study's co-principal investigator Abass Alavi, MD, PhD, a professor of Radiology at Penn. "Our results support the notion that amyloid imaging does not reflect levels of brain function, and therefore it may be of limited value for assessing patients with cognitive decline."

Alzheimer's disease, the most common cause of dementia, is the sixth leading cause of death in the United States, affecting up to 5.8 million Americans currently. As clinicians aim to spot and treat the symptoms of dementia in its earliest stages, PET plays an increasingly pivotal role in diagnosing and monitoring Alzheimer's disease, as well as MCI, a condition that often precedes dementia.

Two of the most significant biomarkers found in Alzheimer's are decreased glucose uptake and the accumulation of amyloid plaques in the brain. PET scans use different radioactive drugs, called radiotracers, to measure these biomarkers within the brain tissue of patients with cognitive impairment. FDG-PET is one of the most commonly used imaging techniques to diagnose Alzheimer's. However, in recent years, several other radiotracers, such as florbetapir, have been developed to detect the deposition of amyloid plaques.

Recently, the effectiveness of amyloid imaging as a strategy for monitoring dementia symptoms has been called into question. While the presence of amyloid plaques in the brain is considered as being characteristic of Alzheimer's, some studies have shown that large amounts of amyloid plaques were present in healthy, non-demented individuals. Conversely, recent clinical trials have shown that the intended removal of amyloid from the brains of patients with Alzheimer's disease led to no change in, or even worsened, cognitive performance.

In this study, the researchers evaluated 63 individuals, including 19 with clinically diagnosed Alzheimer's disease, 23 with MCI, and 21 healthy individuals. The study participants underwent both FDG- and florbetapir-PET imaging. They were then assessed with a Mini Mental Status Examination (MMSE), a widely used diagnostic test for detecting and assessing the severity of cognitive impairment. The researchers used a novel "global quantification approach" to generate data from five different regions of the brain, which were correlated with the results from the MMSE scores.

The study revealed that both FDG- and florbetapir-PET scans are able to effectively discriminate the individuals with dementia from the healthy control group. However, when compared with the MMSE scores, the correlation between low cognitive performance and high levels of amyloid was significantly weaker than the correlation between FDG and low cognitive performance for all groups included in the study. This suggests that FDG-PET is a more sensitive indicator of cognitive decline.

"Amyloid imaging has a value in diagnosing or ruling out Alzheimer's disease, but it's a bit like all or nothing. Our study shows that it can reveal disease, but you wouldn't be able to differentiate between someone who had very mild or very severe symptoms," said co-principal investigator Andrew Newberg, MD, a professor of Radiology at Thomas Jefferson University, who added that these findings have important implications for clinical research.

"In a clinical drug trial, for example, it may be more relevant to do an FDG-PET scan, rather than using amyloid as a marker, to find out whether the therapy is working," Newberg said.

While FDG-PET may not be a perfect diagnostic tool, the study confirms that currently it is the best available method for monitoring symptoms of dementia, according to Alavi.

"Right now, FDG is king when it comes to looking at brain function, not only in Alzheimer's disease, but also diseases like vascular dementia and cancer," Alavi said.

https://www.sciencedaily.com/releases/2019/08/190806121133.htm