dementia views you can use: November 2017

Thursday, November 30, 2017

Safely increase Aricept dosage

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Chase

DEMENTIA DRUGS: Donepezil (Aricept) boosts memory & thinking in Alzheimer's. More donepezil means more boost - along with intensified side-effects. A key trial shows how donepezil can be safely boosted when combined with solifenacin. Find out more.

IRVINE, California -- Donepezil helps Alzheimer's and other types of dementia. Doctors often minimize its use because it can have a variety of side-effects. Progressive research shows that by adding solifenacin to each pill of donepezil, a patient could potentially boost the dosage by as much as 400% without added side-effects.

Here's a simplified explanation of how it works.

Brand Name	Generic Name
Early-to-Midstage Alzheimer's
Aricept®	donepezil
Exelon®	rivastigmine
Remynil or Razadyne®	galantamine
Drugs for Moderate-to-Severe Stage
Namenda® or Ebixa®	memantine

Acetylecholine is used by the brain to send messages from cell to cell.
If there is not enough acetylecholine in the brain, memory and thinking start to fail.
Alzheimer's often experiences dangerous drops in acetylcholine.
Donepezil helps boost the level of acetylcholine throughout the body.
This can help an Alzheimer's brain get back to normal. However, it can also overload other systems in the body, causing nausea, weight-loss and other side-effects.
The brain is separated from the rest of the body by the "blood-brain barrier".
A pill of donepezil travels from the stomach to the entire body. It passes through the blood-brain barrier, boosting acetylcholine in the brain.
Solifenacin is another drug that blocks donepezil. However, it CANNOT pass through the blood-brain barrier.
Therefore, it seems that solifenacin cannot get to the brain and as a result, cannot block donepezil in the brain.
At the same time, solifenacin can block donepezil everywhere else in the body, stopping side-effects like nausea in the stomach.
The result is no nausea or other side-effects in the body. The patient just gets the good effect in the brain.

For now, researchers call this combination of donepezil-plus-solifenacin by the name CPC-201. The new combination will mean that the brain can get the benefits of a lot more donepezil with fewer side-effects.

Chase Pharmaceuticals Corporation (Chase) announced its results from a Phase 2 study of CPC-201.

400%

The CPC-201 Phase 2 results, presented by Thomas Chase, MD, chief scientific officer and co-founder of Chase, and the former Scientific Director and head of the Experimental Therapeutics Branch for the National Institute of Neurological Disorders and Stroke, confirmed that solifenacin attenuated donepezil adverse events, enabling the tolerable administration of doses of donepezil to as much as 400 percent of the current standard treatment of donepezil. Secondary endpoints provided signals of enhanced efficacy, as would be predicted from increased tolerable dosing of donepezil. The data were presented during an oral session at the 2016 Alzheimer’s Association Conference (AAIC) in Toronto, Canada (Abstract a12446).

The primary endpoint of this Phase 2 single-blind, crossover trial was to safely increase the tolerated dose of donepezil from 10 mg/day up to as much as 40 mg/day. This trial consisted of 41 moderate (MMSE 10-20) Alzheimer’s type subjects who were being successfully treated with 10 mg/day of donepezil. The anticholinergic solifenacin was first titrated to 15 mg/day and then donepezil escalated to each subject’s maximum tolerated dose or to the protocol limit of 40 mg/day. Subjects then continued for a three-month maintenance period. All subjects were able to tolerably maintain above the currently approved doses of donepezil and 85 percent of subjects reached and tolerated the maximum allowable donepezil dose of 40 mg/day. Moreover, in the maintenance phase of the trial, subjects experienced significantly less dose-limiting side effects than those that would be predicted for 10 mg/day of donepezil.

A Real Difference

Although this Phase 2 study was not designed nor powered to provide meaningful estimates of anti-dementia efficacy, both the ADAS-Cog and the CGI-I scales in the study yielded positive signals of enhanced efficacy.

During the dose maintenance phase, at a median donepezil dose of 40 mg/day, total gastrointestinal adverse events were greatly attenuated and about 80 percent below those predicted from trials of previously approved doses of 10 mg/day of donepezil. As would be expected with a cholinergic blocker that does not cross the blood-brain barrier, solifenacin had no effect on cognitive function and there were no drug-related serious adverse events (SAE) or clinically significant cardiovascular or laboratory abnormalities. There were no drug related dropouts and no new AEs or evidence of solifenacin toxicity.

“Pre-clinical studies have repeatedly shown that there is a strong dose/efficacy relationship associated with AChEIs. Further, PET scan studies in humans show that at the typical dose of 10 mg/day of donepezil, the central enzymatic inhibition is no greater than about 30 percent, substantially lower than that which would be expected from optimal dosing. Yet, historically, it has not been possible to tolerably increase the dose of donepezil to meaningfully higher levels,” said Douglas Ingram, chief executive officer of Chase. “We believe we have the means to finally unlock the true potential of optimally dosed AChEIs. Moreover, we are employing an efficient development and regulatory pathway and plan to commence a superiority trial versus the current gold-standard treatment for Alzheimer’s, 10 mg/day of donepezil. If successful in Phase 3, CPC-201 could be the new standard for the symptomatic treatment of Alzheimer's disease and benefit millions of suffering patients.”

What Do Aricept, Exelon & Razadyne Do?

Teepa Snow
MEDICATION VIDEO
See Teepa Snow talk about the top medications for Alzheimer's & dementia. In plain English, she explores what they do and how they work. Get clarity on Aricept, Exelon and Razadyne (generic donepezil, rivastigmine and galantamine).

Technical Talk

“We believe that adverse events have long limited AChEI dosing to suboptimal levels, in turn limiting the efficacy of donepezil and other AChEIs,” said Thomas Chase, M.D. “Our Phase 2 findings, together with those from our earlier Phase 1 studies, robustly support our hypothesis that the co-formulation of a peripheral anticholinergic with donepezil enables the safe and tolerable administration of multiples of the current standard of care doses of AChEI such as donepezil.”

The mean change in ADAS-Cog over the course of the study showed improvement versus subject baseline and, adjusted for underlying disease progression using a multi-study meta-analysis, subjects showed a mean (± SEM) benefit of 2.45 points over 10 mg/day donepezil or 5.4 ± .84 points compared to predicted untreated disease progression. Combined Clinical Global Impression (CGI-I) scores from investigators and caregivers at 26 weeks averaged 3.1 ± .20 points, thus improving by .94 ± .20 points (p < .001; n = 16). The responder rate (as measured by those who either did not worsen or improved over the course of the study) was over 90 percent.

MORE INFORMATION:

About CPC-201
Chase’s lead candidate, CPC-201, is a patent-protected combination of donepezil (an AChEI), one of the few pharmaceuticals proven to improve cognition in Alzheimer’s patients, and solifenacin, a peripherally acting cholinergic blocker.

Tuesday, November 28, 2017

Alzheimer's brain vs healthy brain

In a comprehensive analysis of samples from 107 aged human brains, researchers at the Allen Institute for Brain Science, UW Medicine and Kaiser Permanente Washington Health Research Institute have discovered details that will help researchers better understand the biological bases for Alzheimer's disease and dementia in older populations. The analysis also highlights surprising variability in the aged brain, including examples of donors with resilience to pathology. The research is published this month in the journal eLife, and the data underlying the research are publicly available as part of the suite of open data resources at the Allen Brain Atlas portal.

"Since the population of individuals over 90 years of age is rapidly increasing, understanding both healthy aging and age-related disease is essential," says Ed Lein, Investigator at the Allen Institute for Brain Science. "This means we must discover how cognitive decline correlates with the brain pathologies we typically attribute to diseases like Alzheimer's in aged brains, as well as the biology underlying individual vulnerability and resilience to disease." In this analysis, researchers sought to understand whether associations previously identified between cognitive status, gene expression and brain pathologies--such as the plaques and tangles typically found in Alzheimer's disease--held true in a well characterized, aged population. To achieve this goal, researchers developed a state of the art approach combining traditional and quantitative measures to probe the relationships between gene expression and age-related neurodegeneration.

"Several studies exist that compare expression in donor brains aged 60-85 years, but few in the more aged cohort we were able to study here," says Jeremy Miller, Ph.D., Senior Scientist I at the Allen Institute for Brain Science and lead author on the publication. "We found that the more aged brains still showed a correlation between cognitive decline and the Alzheimer's-associated plaques and tangles, although the relationship was not as strong as in younger cohorts."

In addition, the research revealed a surprising relationship between dementia and decreased quality of RNA--a key player in gene expression--in the more aged brain.

"One factor that is not always taken into account when studying gene expression in the aged brain is the quality of the genetic material itself," says Miller. "This variable is not necessarily related to any specific pathology or disease, but these results highlight the importance of properly controlling for RNA quality when studying the aged brain and indicate that degradation of genetic material may be an underappreciated feature of neurodegeneration or dementia."

All of the data underlying the research is part of the Aging, Dementia and TBI resource, freely available through the Allen Brain Atlas data portal. "We want to promote a model of systematic, collaborative, multidimensional study of the diseased brain and open access to data and tools to facilitate discovery across the entire basic and biomedical research community," says Lein.

"We anticipate that this dataset and research model will inform and help shape future brain aging research to propel a deeper understanding of the mechanisms driving neurological disease for improved diagnostic approaches and effective therapeutic strategies," says C. Dirk Keene, M.D., Ph.D., study co-author and Director of UW Medicine Neuropathology.

The study samples come from the Adult Changes in Thought (ACT) study, a longitudinal research effort led by Eric B. Larson, M.D., M.P.H., and Paul K. Crane, M.D., M.P.H., of the Kaiser Permanente Washington Health Research Institute (KPWHRI) (formerly known as Group Health Research Institute) and the University of Washington School of Medicine to collect data on thousands of aging adults, including detailed information on their health histories and cognitive abilities.

"This collaboration with the Allen Institute for Brain Science has allowed us to gain insights never before possible into the relationships between neuropathology, gene expression, RNA quality, and clinical features tracked in the ACT study over more than 20 years," says Larson, who has led the National Institute of Aging-supported study from its start in 1986 and is Vice President for Research and Health Care Innovation at Kaiser Permanente Washington. "We are grateful to the thousands of volunteer subjects who worked with us and those who donated their brains to science. The results are transformative in improving our understanding of the aging brain, a theme of the ACT study, which aims to learn ways to reduce the burden of dementia for individuals and society overall."

###

About the Allen Institute for Brain Science

The Allen Institute for Brain Science is a division of the Allen Institute (alleninstitute.org), an independent, 501(c)(3) nonprofit medical research organization, and is dedicated to accelerating the understanding of how the human brain works in health and disease. Using a big science approach, the Allen Institute generates useful public resources used by researchers and organizations around the globe, drives technological and analytical advances, and discovers fundamental brain properties through integration of experiments, modeling and theory. Launched in 2003 with a seed contribution from founder and philanthropist Paul G. Allen, the Allen Institute is supported by a diversity of government, foundation and private funds to enable its projects. The Allen Institute for Brain Science's data and tools are publicly available online at brain-map.org.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Sunday, November 26, 2017

Ronald Reagan and Alzheimer's

Caregivers, and healthcare professionals,here is some great information

Here is a great dementia resource for caregivers and healthcare professionals,

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Here is information on being the best caregiver you can be

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The Dementia Caregiver's Little Book of Hope [Kindle Edition]

IN 1983, PRESIDENT REAGAN ESTABLISHED NOVEMBER AS NATIONAL ALZHEIMER'S AWARENESS MONTH. IN 1994, HE TOLD THE WORLD HE HAD IT. SEE VIDEO + INSPIRING LETTER:
Read the letter.

Nov. 5 1994

My Fellow Americans,

I have recently been told that I am one of the Americans who will be afflicted with Alzheimer's Disease.

Upon learning this news, Nancy & I had to decide whether as private citizens we would keep this a private matter or whether we would make this news known in a public way.

Continued below video...

In the past Nancy suffered from breast cancer and I had my cancer surgeries. We found through our open disclosures we were able to raise public awareness. We were happy that as a result many more people underwent testing. They were treated in early stages and able to return to normal, healthy lives.

So now, we feel it is important to share it with you. In opening our hearts, we hope this might promote greater awareness of this condition. Perhaps it will encourage a clearer understanding of the individuals and families who are affected by it.

At the moment I feel just fine. I intend to live the remainder of the years God gives me on this earth doing the things I have always done. I will continue to share life's journey with my beloved Nancy and my family. I plan to enjoy the great outdoors and stay in touch with my friends and supporters.

Unfortunately, as Alzheimer's Disease progresses, the family often bears a heavy burden. I only wish there was some way I could spare Nancy from this painful experience. When the time comes I am confident that with your help she will face it with faith and courage.

In closing let me thank you, the American people for giving me the great honor of allowing me to serve as your President. When the Lord calls me home, whenever that may be I will face it with the greatest love for this country of ours and eternal optimism for its future.

I now begin the journey that will lead me into the sunset of my life. I know that for America there will always be a bright dawn ahead.

Thank you, my friends. May God always bless you.

Sincerely,

Ronald Reagan

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Friday, November 24, 2017

Is Alzheimer's an energy metabolism disorder?

Summary: Failure of mitochondrial function may contribute to the development of late onset Alzheimer’s disease, a new study reports.

Source: McLean Hospital.

A team of investigators from McLean Hospital and Harvard Medical School, led by Kai C. Sonntag, MD, PhD, and Bruce M. Cohen, MD, PhD, has found a connection between disrupted energy production and the development of late-onset Alzheimer’s disease (LOAD). The findings appear in the current issue of Scientific Reports.

“These findings have several implications for understanding and developing potential therapeutic intervention in LOAD,” explained Sonntag, an associate stem cell researcher at McLean Hospital and an assistant professor of psychiatry at Harvard Medical School. “Our results support the hypothesis that impairment in multiple interacting components of bioenergetics metabolism may be a key mechanism underlying and contributing to the risk and pathophysiology of this devastating illness.”

For three decades, it has been thought that the accumulation of small toxic molecules in the brain, called amyloid beta, is central to the development of Alzheimer’s disease (AD). Strong evidence came from studying familial or early-onset forms of AD (EOAD) that affect about five percent of AD patients and have associations with mutations leading to abnormally high levels or abnormal processing of amyloid beta in the brain. However, the “Amyloid hypothesis” has been insufficient to explain the pathological changes in the more common LOAD, which affects more than 5 million seniors in the United States.

“Because late-onset Alzheimer’s is a disease of age, many physiologic changes with age may contribute to risk for the disease, including changes in bioenergetics and metabolism,” said Cohen, director of the Program for Neuropsychiatric Research at McLean Hospital and the Robertson-Steele Professor of Psychiatry at Harvard Medical School. “Bioenergetics is the production, usage, and exchange of energy within and between cells or organs, and the environment. It has long been known that bioenergetic changes occur with aging and affect the whole body, but more so the brain, with its high need for energy.”

According to Sonntag and Cohen, it has been less clear what changes in bioenergetics are underlying and which are a consequence of aging and illness.

In their study, Sonntag and Cohen analyzed the bioenergetic profiles of skin fibroblasts from LOAD patients and healthy controls, as a function of age and disease. The scientists looked at the two main components that produce energy in cells: (1) glycolysis, which is the mechanism to convert glucose into fuel molecules for consumption by mitochondria, and (2) burning of these fuels in the mitochondria, which use oxygen in a process called oxidative phosphorylation or mitochondrial respiration. The investigators found that LOAD cells exhibited impaired mitochondrial metabolism, with a reduction in molecules that are important in energy production, including nicotinamide adenine dinucleotide (NAD). LOAD fibroblasts also demonstrated a shift in energy production to glycolysis, despite an inability to increase glucose uptake in response to the insulin analog IGF-1. Both the abnormal mitochondrial metabolism and the increase of glycolysis in LOAD cells were disease- and not age-specific, while diminished glucose uptake and the inability to respond to IGF-1 was a feature of both age and disease.

“The observation that LOAD fibroblasts had a deficiency in the mitochondrial metabolic potential and an increase in the glycolytic activity to maintain energy supply is indicative of failing mitochondria and fits with current knowledge that aging cells increasingly suffer from oxidative stress that impairs their mitochondrial energy production,” said Sonntag.

For three decades, it has been thought that the accumulation of small toxic molecules in the brain, called amyloid beta. NeuroscienceNews.com image is in the public domain.

Cohen added that because the brain’s nerve cells rely almost entirely on mitochondria-derived energy, failure of mitochondrial function, while seen throughout the body, might be particularly detrimental in the brain.

The study’s results link to findings from other studies that decreasing energy-related molecules (and specifically NAD) are features of normal aging by suggesting that abnormalities in processes involving these molecules may also be a factor in neurodegenerative diseases like LOAD. Whether modulating these compounds could slow the aging process and prevent or delay the onset of LOAD is unknown. However, several clinical trials are currently under way to test this possibility. Other changes are unique to AD, and these, too, may be targets for intervention.

While these findings are significant, the paper’s authors emphasize that the pathogenesis of LOAD is multifactorial, with bioenergetics being one part of risk determination and note that the skin fibroblasts studied are not the primary cell type that is affected in LOAD.

“However, because bioenergetics changes are body-wide, observations made in fibroblasts may also be relevant to brain cells,” said Sonntag. “In fact, metabolic changes like diminished glucose uptake and insulin/IGF-1 resistance may underlie the association between various disorders of aging, such as type 2 diabetes and AD.”

Sonntag and Cohen are already in the midst of follow-up work aiming to study these bioenergetics features in brain nerve cells and astrocytes generated from LOAD patient-derived induced pluripotent stem cells, as an aging and disease model in the dish. It is the group’s hope that findings from these studies will reveal further insight into the role of bioenergetics in LOAD pathogenesis and novel targets for intervention–both prevention and treatment.

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

In addition to Mareike Bacha-Trams and Iiro Jääskeläinen, the research team included Enrico Glerean, Juha Lahnakoski, Elisa Ryyppö, Mikko Sams and Robin Dunbar, Oxford University Professor known for Dunbar’s Number.

Source: Laura Neves – McLean Hospital
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is credited to the researchers.
Original Research: Full open access research for “Late-onset Alzheimer’s disease is associated with inherent changes in bioenergetics profiles” by Kai-C. Sonntag, Woo-In Ryu, Kristopher M. Amirault, Ryan A. Healy, Arthur J. Siegel, Donna L. McPhie, Brent Forester & Bruce M. Cohen in Scientific Reports.

CITE THIS NEUROSCIENCENEWS.COM ARTICLE

Wednesday, November 22, 2017

Nanowired drugs for Alzheimer's

Summary: Using titanate nanowires treated with cerebrolysin, researchers have been able to target delivery to the brain and through the central nervous system. Researchers report the use of nanowires to deliver drugs could be beneficial in the treatment of Alzheimer’s, Parkinson’s and other neurodegenerative diseases.

Source: University of Arkansas.

Millions of Americans suffer from neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Researchers have identified promising new treatments, such as cerebrolysin, but current clinical approaches are ineffective because critical concentrations of the drug dissipate within the body before reaching the blood-brain barrier and central nervous system.

To address this problem, researchers have focused on various delivery vehicles for sustained and targeted drug release. An effective, targeted approach would eliminate the need for inefficient, high dosages that cause adverse side effects.

In recent years, biomedical engineers have experimented with nanomaterials as an approach to targeted delivery. Under the direction of Ryan Tian, associate professor of chemistry at the University of Arkansas, doctoral student Asya Ozkizilcik has improved the nanowiring of drugs for an international team of researchers who are working on a new method for treating neurodegenerative diseases.

Ozkizilcik worked with titanate, a bioceramic material made of titanium dioxide. Titanate has many advantages. Its nanowires are chemically inert and therefore do not interact with biological components. In addition to biocompatibility, the nanowires are resistant to corrosion in biological fluids, which is ideal for sustained, in vivo drug release without harming cells or tissues.

“We believe titanate nanowires could be considered as potential drug delivery tools for neurodegenerative diseases and may be translated into clinical use in future,” Ozkizilcik said. NeuroscienceNews.com image is in the public domain.

Ozkizilcik made the titanate nanowires in an autoclave treatment and then loaded cerebrolysin onto the nanowires. Though detailed mechanisms are unclear, the nanoparticles may prolong the intact delivery of cerebrolysin all the way to blood-brain barrier, where high concentrations of the drug are then released into the brain. The drug’s efficacy was tested on rat models with co-administration of mesenchymal stem cells. Mesenchymal stem cells have been used for developing therapeutics for various autoimmune and other diseases.

Ozkizilcik’s research is part of the international team’s broader goal of finding a more effective treatment for neurodegenerative diseases such as Alzheimer’s and Parkinson’s. The international team has also demonstrated efficacy of this treatment on a Parkinson’s disease model after traumatic brain injury.

“We believe titanate nanowires could be considered as potential drug delivery tools for neurodegenerative diseases and may be translated into clinical use in future,” Ozkizilcik said.

Monday, November 20, 2017

Unusual sigh \of Alzheimer's

This simple test can help to predict Alzheimer’s disease.

Being unaware of memory loss is actually an important warning sign for developing Alzheimer’s disease, new research finds.

People who were unaware of their own memory problems — known as anosognosia — were 64% more likely to develop Alzheimer’s within 5 years.

On the other hand, if you are worried about memory loss, but your partner isn’t, then it’s probably not Alzheimer’s.

Dr. Philip Gerretsen, the study’s lead author, said:

“If patients complain of memory problems, but their partner or caregiver isn’t overly concerned, it’s likely that the memory loss is due to other factors, possibly depression or anxiety.

They can be reassured that they are unlikely to develop dementia, and the other causes of memory loss should be addressed.”

The conclusions come from the largest ever study on the self-awareness of dementia.

Over one thousand people aged 55 to 90 were involved.

Being unaware of memory problems predicted the shift from mild cognitive impairment to Alzheimer’s disease, the researchers found.

Saturday, November 18, 2017

Green tea blocks Alzheimer's

Caregivers, and healthcare professionals,here is some great information

Here is a great dementia resource for caregivers and healthcare professionals,

Your residents will love the Amazon Kindle Fire

Here is information on being the best caregiver you can be

Here is a way for nurses administrators, social workers and other health care professionals to get an easyceu or two

Follow alzheimersideas on twitter
The Dementia Caregiver's Little Book of Hope [Kindle Edition]

McMaster University

DIET NEWS: McMaster University uncovered new clues on how EGCG in green tea blocks the Alzheimer’s cascade. Their research was on the cover of the Journal of the American Chemical Society. Learn how it works.

Green tea is widely considered to be beneficial for the brain. The antioxidant and detoxifying properties of green tea extracts help fight catastrophic diseases such as Alzheimer’s. However, scientists have never fully understood how they work at the molecular level and how they could be harnessed to find better treatments.

Research from McMaster University is shedding new light on those underlying mechanisms. Preclinical evidence suggests that the green tea compound known as EGCG interferes with the formation of toxic assemblies (oligomers), one of the prime suspects in the early steps of the molecular cascade that leads to cognitive decline in Alzheimer’s patients.

“At the molecular level, we believe EGCG coats toxic oligomers and changes their ability to grow and interact with healthy cells,” explains Giuseppe Melacini, lead author and a professor in the Departments of Chemistry and Chemical Biology as well as of Biochemistry and Biomedical Sciences at McMaster, who has worked on Alzheimer’s-related research for 15 years.

The findings, which are the results of a decade of advancements in nuclear magnetic resonance (NMR) methodology and are featured in the cover page of the Journal of the American Chemical Society, could lead to new therapies and further drug discovery, say researchers.

Despite decades of research, the causes of Alzheimer’s remain not fully understood, and treatment options are limited. According to the latest census numbers, seniors living in Canada now outnumber children, dramatically increasing the need for effective drugs and prevention. By some estimates, the number of Canadians with dementia is expected to rise to 937,000 by the year 2031, an increase of 66 per cent compared to current numbers.

“We all know that currently there is no cure for Alzheimer’s once symptoms emerge, so our best hope is early intervention. That could mean using green tea extracts or their derivatives early on, say 15 to 25 years before any symptoms ever set in” says Melacini.

Next, researchers hope to tackle nagging problems such as how to modify EGCG and similar molecules so they can be used effectively as a food additive, for example. EGCG is unstable at room temperature and notoriously difficult to deliver into the human body, particularly the brain.

“Food additives could prove to be a crucial therapy or adjuvant” says Melacini. “It will be important to capitalize on them early in life to increase the odds of healthy aging, in addition to exercise and a healthy lifestyle.”

REFERENCE:

Molecular Mechanism for the (−)-Epigallocatechin Gallate-Induced Toxic to Nontoxic Remodeling of Aβ Oligomers, Rashik Ahmed, Bryan VanSchouwen, Naeimeh Jafari, Xiaodan Ni, Joaquin Ortega, and Giuseppe Melacini. August 25, 2017. Journal of the American Chemical Society.

Thursday, November 16, 2017

Does too much iron cause dementia

IRON accumulation within neurons can cause brain aging and dementia. A fast-aging African fish has helped researchers discover why. Find out how it works and what you should do about it.

During aging as well as during Alzheimer’s or Parkinson’s disease, iron accumulates in the human brain. Now, researchers found that in vertebrates, a microRNA called miR-29 inhibits these deposits – possibly offering new ways to treat Alzheimer’s and Parkinson’s disease as well as strokes. Results were published in the Journal BMC Biology on February 13, 2017.

Anti-Aging Molecule in the Brain

As we get older, our brain ages. Cognitive abilities decline and the risk of developing neurodegenerative diseases like dementia, Alzheimer’s and Parkinson’s disease or having a stroke steadily increases.

Aging in fast motion: The natural lifespan of N. furzeri is only few months (left: male of long-lived strain, aged 6 months; right: geriatric male aged 13 months). The African fish was used as aging model by researchers from Jena (Germany) and Pisa (Italy) to show that neurons are protected from iron-accumulation by an anti-aging microRNA. The results could offer a new approach for the treatment of neurodegenerative diseases. Credit: FLI/Grimm/Kästner

A possible cause is the accumulation of iron molecules within neurons, which seems to be valid for all vertebrates. In a collaborative research project within the consortium JenAge, researchers from the Leibniz Institute on Aging – Fritz Lipmann Institute (FLI) in Jena, Germany, and the Scuola Normale Superiore (SNS) in Pisa, Italy, found that this iron accumulation is linked to a microRNA called miR-29. This little molecule has so far been known to act as a tumor suppressor, hindering the proliferation of cancer cells.

However, clearly, miR-29 also regulates whether or not iron can be deposited in neurons. Using the African fish Nothobranchius furzeri – the shortest-living vertebrate that can be kept under laboratory conditions – the team of Alessandro Cellerino showed a large increase of iron deposits in fish where miR-29 had been suppressed, which led to premature brain aging. In contrast, healthy fish showed the more miR-29 in their neurons, the older they were. Hence, miR-29 acts as a kind of anti-aging molecule during aging, inhibiting the accumulation of iron in neurons.

New Way to Treat Dementia?

„We strongly believe that our results are relevant for humans as well“, says Alessandro Cellerino, Professor of Physiology at SNS in Pisa and guest scientist at the FLI, who is one of the study’s leaders. In fact, the link between an increased iron accumulation and neurodegenerative diseases or strokes in humans has been known for some time; there are also results showing a reduced concentration of miR-29 in these diseases. However, it is totally new that miR-29 acts as molecular switch that inhibits iron accumulation. “These results are surprising – and very promising, because the development of miR-29-based pharmaceuticals for cancer therapy is already ongoing. This may offer a head start for the development of new therapies for Parkinson’s or Alzheimer’s disease and for the treatment of strokes as well”, Cellerino adds.

First Biomedical Discovery in New Fish Model Has Great Potential

African killifish Nothobranchius furzeri has only recently been introduced as animal model in aging research. It was the deciphering of the fish’s genome in late 2015 by the Leibniz Institute on Aging (FLI) that laid the foundation for genetic studies in this fast-aging vertebrate. “The investment of ten years, which it took us and our collaborators to decipher the genome, now starts to pay off”, explains Prof. K. Lenhard Rudolph, who is the FLI’s Scientific Director. And Mario Baumgart, a Postdoc at the FLI that was involved in the study, adds: “There’s no other vertebrate showing such a rapid aging as this little fish. It is like aging in fast motion. Moreover, 90% of human genes can be found in the fish as well, making almost all knowledge gained from N. furzeri transferable to humans.” This is why the results about the molecular switch miR-29, which were published on February 13, 2017 in the journal BMC Biology are so promising and mean a further step towards the treatment of neurodegenerative diseases.

Should I Worry?

Older people (male or female) are not prone to accumulating excess iron from a balanced healthy diet, moderate supplementation or alcohol consumption. This age group can potentially have toxic levels of iron in their organs and glands, if they abuse alcohol, consuming excessively of nicotine products (to stop smoking), on hormone replacement therapy, have B12 deficiencies, or are receiving repeated blood transfusion.

Although iron is an essential element for healthy life, too much iron can overwhelm the body’s natural storage capability leading to oxidative stress, tissue damage, and early aging. Iron is particularly dangerous and can catalyze these processes even in small amounts (less than a few extra grams) when mixed with other risk factors such as obesity, family history of diabetes or heart disease, inadequate consumption of antioxidants (fruits and vegetables), hormone replacement therapy, unhealthy cholesterol levels, smoking and regular alcohol consumption and for women
who no longer menstruate

.

Damage from Too Much Iron

Cell and tissue damage caused by iron can either initiate and/or contribute to the following causes of that can shorten lifespan or cause sudden death:

Cirrhosis of the liver
Cardiovascular diseases
Cancer (particularly cancers of the liver and colon)
Type II diabetes
Septicemia (excessive iron nourishes dangerous microbe colonization)
Early onset neurodegenerative diseases (Alzheimer’s and Parkinson’s diseases, among others)

INFO-BOX: Related

Iron: More When Young, Less When Old

Excess iron is linked to Alzheimer's. So researchers used supplements to increase blood levels of iron, and then chelators to lower those levels. Find out just how important it is to strike the right dietary balance of iron at the right age.

Individual symptoms and degree of expression will vary between people (as will the amounts of stored iron). Excessive body iron accumulation can also lead to depression, loss of muscle mass and strength, enlargement and impairment of liver and spleen, loss of body hair, hypothyroidism, loss of libido (sexual interest) and function, with noticeable changes (darkening) of skin color, chronic fatigue and joint pain (especially in the first two knuckles of the hand referred to as “iron fist”.) Too much iron should be suspect in the presence of any of these symptoms. In women, the greatest risk for and indicator of suspect iron overload is when the monthly period stops for whatever reason: taking birth control pills, hysterectomy or menopause. With the monthly blood loss from a period iron is also lost, keeping excess iron under control.

Fortunately for most, iron metabolism is tightly regulated by their genes. Those lucky ones are similar to people who seem to be able to eat as much as they want and not get fat. Some people can consume plenty of iron-packed red meat and even imbibe in some potentially unhealthy habits, and yet not be further harmed by the invisible threat of adding too much iron to that potentially unhealthy mix. That’s because their metabolisms don’t permit absorption of any more iron than what’s needed for the body to function properly, which includes about one extra gram stored in reserve.

For older people with genetic hemochromatosis who also have a tendency or condition causing blood loss, the extra bit of stored iron may protect them from iron deficiency and anemia.

Diseases or conditions that can produce too much iron in the elderly include:

Menopause (females)