Tag Archives: dementia

Alzheimer’s May Be Caused By Dental Infection

In a new study scientists reveal yet another reason to keep up on dental hygiene. Bacteria that cause a common yet largely preventable gum infection may also play a role in Alzheimer’s disease. The discovery also offers hope for a treatment that could slow neurodegeneration.

There were many clues in the [features of Alzheimer’s disease] that an infection is at work,” said Casey Lynch, an entrepreneur and co-founder of Cortexyme, a biotech company headquartered at the Verily Life Sciences campus in South San Francisco, who led the new research. “Many of the genetic risk factors for Alzheimer’s are related to immune system function,” she added, which suggests “immune system dysfunction might put people more at risk.

Alzheimer’s disease, an irreversible and progressive brain disorder that leads to memory loss and diminished thinking skills, affects at least 5 million Americans. Clumps of a brain protein known as amyloid plaques are a hallmark sign of the disease. Billions of research dollars have gone towards finding a treatment that destroys these mind-robbing masses. But there’s still no cure.

Not enough people are asking what is upstream of the plaques … and [brain] inflammation,” said Lynch, who has a background in Alzheimer’s research and was frustrated by the string of failed therapies for the disease. Nearly six years ago, Lynch received a call from Stephen Dominy, a psychiatrist at the University of California, San Francisco, who had studied the link between HIV and dementia.

I think I’ve found a bacterial cause of Alzheimer’s,” Dominy, who co-founded Cortexyme with Lynch and now serves as the company’s Chief Scientific Officer, told her. Dominy had spent about 15 years searching for infections that might lead to Alzheimer’s until evidence for a bacterium known as P. gingivalis became “undeniable,” according to Lynch. P. gingivalis causes periodontitis, an infection that destroys the gums and can lead to tooth loss.

When the team examined the brains and cerebrospinal fluid of Alzheimer’s patients, they found DNA from the bacterium. They also discovered bacterial enzymes called gingipains that destroy brain cells were present, too. And when they watched P. gingivalis infections play out in mice, it triggered neurodegeneration in the hippocampus, a brain structure central to memory. It also led to Alzheimer’s hallmark amyloid beta plaque production and inflammation, the researchers discovered.

The scientists then designed and created a new molecule that blocks the gingipain enzymes. The antibiotic reduced the amount of bacteria in infected mice and stopped the formation of amyloid beta plaques while reducing inflammation, the team reports Wednesday in the journal Science Advances.

Source: https://www.discovermagazine.com/

Rare genetic mutation holds clues to preventing Alzheimer’s

Could one woman’s rare genetic mutation one day have a global impact on dementia risk? It’s possible, say investigators who report on a potentially groundbreaking case of a woman whose genetic mutation staved off dementia for decades, even though her brain had already been damaged by Alzheimer’s disease. While most Alzheimer’s cases are not driven by genetic predisposition, one woman in Colombia is among about 1,200 in her country who do face a genetically higher risk for early-onset Alzheimer’s. Why? They all carry the E280A mutation of a gene called Presenilin 1 (PSEN1), which is known to increase the chances for Alzheimer’s at a far younger age than usual.

We identified an individual that was predisposed to develop Alzheimer’s in her 40s,” noted study author Dr. Joseph Arboleda-Velasquez. He’s an assistant professor of ophthalmology with the Schepens Eye Research Institute of Mass Eye and Ear at Harvard Medical School, in Boston.

But, strangely, the woman “remained unimpaired until her 70s,” Arboleda-Velasquez added. The twist: the woman had, in fact, developed clear telltale signs of Alzheimer’s in her brain. She just hadn’t developed dementia. For example, while she had fewer neural “tangles” in her brain than is typical for Alzheimer’s patients, by the time she hit her 40s she did have the same unusually high level of brain amyloid-beta deposits as her E280A peers. Such deposits are a key signature of Alzheimer’s. So why didn’t she develop middle-aged dementia like her peers?

To unravel the mystery, Arboleda-Velasquez and his colleagues ran an in-depth genetic analysis on the woman. And what they found is that she had not just one mutation, but two. In addition to the E280A mutation, she also carried the so-calledChristchurchmutation in the APOE3 gene. But there’s more. Not only did she carry the Christchurch mutation, but she had two of them. Some of her E280A peers (about 6%) also carried a single copy of Christchurch. But she was the only one who carried two, the investigators found. “It is ultra-rare, with an approximate prevalence of less than one in every 200,000 individuals,” Arboleda-Velasquez said.

And having one such rare mutation did not appear to be enough. No protection against dementia was linked to only one Christchurch mutation. But as this woman’s case suggests, having two such mutations did seem to throw up a shield against Alzheimer’s, preserving her ability to remember things and think clearly for a few decades, long after her E280A peers had started experiencing cognitive decline.

Source: https://www.cbsnews.com/

Walking Patterns Identify Specific Dementia Type

Walking may be a key clinical tool in helping medics accurately identify the specific type of dementia a patient has, pioneering research has revealed.

Gait Lab

For the first time, scientists at Newcastle University have shown that people with Alzheimer’s disease or Lewy body dementia have unique walking patterns that signal subtle differences between the two conditions. The research, published today in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, shows that people with Lewy body dementia change their walking steps more – varying step time and length – and are asymmetric when they move, in comparison to those with Alzheimer’s disease. It is a first significant step towards establishing gait as a clinical biomarker for various subtypes of the disease and could lead to improved treatment plans for patients.

The way we walk can reflect changes in thinking and memory that highlight problems in our brain, such as dementia. “Correctly identifying what type of dementia someone has is important for clinicians and researchers as it allows patients to be given the most appropriate treatment for their needs as soon as possible”, says Dr Ríona McArdle, Post-Doctoral Researcher at Newcastle University’s Faculty of Medical Sciences, who led the Alzheimer’s Society-funded research. The results from this study are exciting as they suggest that walking could be a useful tool to add to the diagnostic toolbox for dementia. It is a key development as a more accurate diagnosis means that we know that people are getting the right treatment, care and management for the dementia they have.

Current diagnosis of the two types of dementia is made through identifying different symptoms and, when required, a brain scan. For the study, researchers analysed the walk of 110 people, including 29 older adults whose cognition was intact, 36 with Alzheimer’s disease and 45 with Lewy body dementia. The participants took part in a simple walking test at the Gait Lab of the Clinical Ageing Research Unit, an NIHR-funded research initiative jointly run by Newcastle Hospitals NHS Foundation Trust and Newcastle UniversityParticipants moved along a walkway – a mat with thousands of sensors inside – which captured their footsteps as they walked across it at their normal speed and this revealed their walking patterns.

Source: https://www.ncl.ac.uk/

Virtual Reality Is Life-Changing For People With Dementia

Virtual reality, smart clothes and reminiscence therapy are offering respite to patients and carers. One of millions of people who die each year from the neurodegenerative disease, Alzheimer’s, for which a cure is not possible. The condition, one of a number of forms of dementia, is caused by rogue proteins that lodge and tangle in the neural networks of the brain, causing irreparable damage to the billions of neurons which transmit the electrical signals that build memories. These cells gradually die, causing memory loss and personality change, eventually halting the brain’s basic functions.

CLICK ON THE IMAGE TO ENJOY THE VIDEO

Despite decades of medical research into treatments to slow the disease’s progressive course or prevent it entirely – the field from which Pfizer notably withdrew in January, after years of setbacks – it is not yet known what causes these proteins to gather, and therefore how to remove or block them. And despite Alzheimer’s being the world’s fifth biggest killer, funding levels for research have lagged shockingly behind those for both cancer and the next biggest area of medical research, cardiovascular disease.

In the meantime, the greatest cost is in providing care and therapy for those suffering from the disease – a global total currently estimated at $818 billion; the equivalent to over one per cent of global GDP. If no effective treatment and preventive solution is found this sum will only increase, as ten million new cases of dementia are diagnosed each year.

UK healthcare start-up, Virtue, applies the latest immersive technologies to the process of ‘reminiscence therapy’. While the traditional approach draws on physical visual stimulus such as photo books, or even involves substantial investment in constructing full-scale sets that recreate nostalgic scenes, Virtue has developed a new type of memory portal using virtual reality 

It’s only now that the phone in your pocket is advanced enough and VR headsets are reducing in price that we can really democratise access to this type of impactful therapy,” Virtue‘s co-founder and CTO Scott Gorman says. Virtue’s app, LookBack VR, offers a wide variety of 360 VR content and filmic experiences which chime with the memories of the target age group of the patient – arranged by destination, theme, activity or decade. Viewers can choose from experiences ranging from spending time on Brighton beach in the 1970s, to finding themselves in a 1950s tearoom, and can create a personalised playlist or ‘itinerary for time travel’ with the help of their family or carer. Their companion can see their VR headset view on a companion app via tablet, along with a series of suggested questions to help stimulate relevant conversation about that era.

Our vision is for LookBack VR to become a global platform that can help people with dementia anywhere,” co-founder and CEO Arfa Rehman shares. “We are starting to seek partnerships with organisations and individuals to gather content from around the world.”

Source: https://www.wired.co.uk/

New Theory To Prevent Alzheimer’s

Alzheimer’s disease, the most common cause of dementia among the elderly, is characterized by plaques and tangles in the brain, with most efforts at finding a cure focused on these abnormal structures. But a University of California, Riverside, research team has identified alternate chemistry that could account for the various pathologies associated with the diseasePlaques and tangles have so far been the focus of attention in this progressive disease that currently afflicts more than 5.5 million people in the United States. Plaques, deposits of a protein fragment called beta-amyloid, look like clumps in the spaces between neurons. Tangles, twisted fibers of tau, another protein, look like bundles of fibers that build up inside cells.

The dominant theory based on beta-amyloid buildup has been around for decades, and dozens of clinical trials based on that theory have been attempted, but all have failed,” said Ryan R. Julian, a professor of chemistry who led the research team. “In addition to plaques, lysosomal storage is observed in brains of people who have Alzheimer’s disease. Neurons — fragile cells that do not undergo cell division — are susceptible to lysosomal problems, specifically, lysosomal storage, which we report is a likely cause of Alzheimer’s disease.”

An organelle within the cell, the lysosome serves as the cell’s trashcan. Old proteins and lipids get sent to the lysosome to be broken down to their building blocks, which are then shipped back out to the cell to be built into new proteins and lipids. To maintain functionality, the synthesis of proteins is balanced by the degradation of proteins.

The lysosome, however, has a weakness: If what enters does not get broken down into little pieces, then those pieces also can’t leave the lysosome. The cell decides the lysosome is not working and “stores it, meaning the cell pushes the lysosome to the side and proceeds to make a new one. If the new lysosome also fails, the process is repeated, resulting in lysosome storage.

The brains of people who have lysosomal storage disorder, another well-studied disease, and the brains of people who have Alzheimer’s disease are similar in terms of lysosomal storage,” Julian said. “But lysosomal storage disorder symptoms show up within a few weeks after birth and are often fatal within a couple of years. Alzheimer’s disease occurs much later in life. The time frames are, therefore, very different.”

Julian’s collaborative team of researchers in the Department of Chemistry and the Division of Biomedical Sciences at UC Riverside posits that long-lived proteins, including beta-amyloid and tau, can undergo spontaneous modifications that can make them undigestible by the lysosomes. “Long-lived proteins become more problematic as we age and could account for the lysosomal storage seen in Alzheimer’s, an age-related disease,” Julian said. “If we are correct, it would open up new avenues for treatment and prevention of this disease.”

Study results appear in ACS Central Science, a journal of the American Chemical Society.

Source: https://news.ucr.edu/

I-Phone Apps Could Identify Alzheimer’s

Drugmaker Eli Lilly said early results from a study suggest that Apple Inc devices, including the iPhone, in combination with digital apps could differentiate people with mild Alzheimer’s disease dementia and those without symptoms. The study, tested in 113 participants over the age of 60, was conducted by Apple along with Eli Lilly and Evidation Health. The Apple devices were used along with the Beddit sleep monitoring device and digital apps in the study.

The researchers looked at device usage data and app history of the study participants over 12 weeks. People with symptoms tended to have slower typing than health volunteers, and received fewer text messages in total.

The participants were also asked to answer two one-question surveys daily as well as perform simple activities every two weeks, such as dragging one shape to the other and tapping a circle as fast as possible on an app. The study also aimed to differentiate people with mild cognitive impairment, the pre-dementia stage of Alzheimer’s disease.

Source: https://www.reuters.com/

The Brain In Your Gut

From moods to memory, the brain in our guts has a big impact on the brain in our heads. Pioneering neuroscientist Associate Professor Elisa Hill-Yardin from RMIT in Australia has spent years delving deep into the gut-brain connection, an emerging field in health research. Here she shares the five critical things we should know about our “gut brain”.

The gut has similar types of neurons to the brain. The gut brain is a big nervous system, about the same size as the spinal cord, which controls the contractions of the gut and its secretions. There are very rare gene mutations that affect brain connectivity and we’ve learned that the vast majority of those gene mutations are also found in the gut. If those mutations change the wiring in the brain, they’re also likely to change the wiring and the action of the gut brain – the enteric nervous system. To date, we’ve only ever examined the effect of those mutations in the brain. Now we’re starting to look at them in our second brain, the gut.

We now know that microbes in the gut do change our mood and behaviour, and microbes even change brain activity. There’s a great study that looked at women, doing MRI brain scans and showing that if they ate yoghurt for a certain number of days their resting brain activity was different – which is amazing! But we also know from animal studies that microbes have an impact on mental health. You can breed mice that are germ free and we know that those mice show differences in their anxiety behaviours – in other words, they’re less anxious without the microbes. So you could say we’re being controlled by the microbes in our gut. They’re much more important to our feelings than we ever thought.

What’s come out in research in recent years, though it’s been known for a long time in the autism community, is that the majority of children with autism have serious gut problems. Now we don’t know the cause of autism but we do know that there are hundreds and hundreds of rare gene mutations that alter brain connectivity. And we now know that some of those mutated genes are also found in the gut. We’re also learning that diseases that affect cognition and memory, like dementia, may also have a gut component. Researchers are starting to look at traditional brain diseases like Alzheimer’s, Parkinson’s, Multiple Sclerosis, and finding difference in the microbes in the gut. So they’re starting to think about how we can make changes in our microbes to make changes to our brain health.

The Gut-Brain Axis team that I lead at RMIT is focused on understanding how the enteric nervous system is altered in neurological disorders such as autism. This includes researching how the gut nervous system interacts with microbes in the intestine and changes in inflammatory pathways. We’re trying to identify the basic mechanisms, examining the connections between the gastrointestinal tract and changes in mood and behaviour, including the impact of genetics on microbiota in the gut. The ultimate the aim is to find novel therapies that can improve daily life for people with autism, but our work also has broader application for other neurological disorders, such Parkinson’s disease.

Many of the great enteric physiologist pioneers are in Australia and they were the first to describe different types of neurons based on their activity and neurochemical content. This work has been done on animal models, due to the possibilities of emulating human genetic diseases in these models. So, a lot of basic anatomy and physiology has been studied. But what we need now is to move the field towards using the latest sophisticated techniques and capitalising on the recent interest in the gut-brain axis, which of course involves understanding how the gastrointestinal tract works in concert with the trillions of microbes that live inside it.

Professor Elisa Hill-Yardin has presented her work to the US Air Force Office of Scientific Research

Source: https://www.rmit.edu.au/

Early-Stage Detection Of Alzheimer’s In The Blood

Two major studies with promising antibodies have recently failed – possibly because they have been administered too late. A new very early-detection test gives rise to hope. Using current techniques, Alzheimer’s disease, the most frequent cause of dementia, can only be detected once the typical plaques have formed in the brain. At this point, therapy seems no longer possible. However, the first changes caused by Alzheimer’s take place on the protein level up to 20 years sooner. A two-tier method developed at Ruhr-Universität Bochum (RUB) can help detect the disease at a much earlier stage. The researchers from Bochum published their report in the March 2019 edition of the journal “Alzheimer’s and Dementia: Diagnosis, Assessment and Disease Monitoring”.

This has paved the way for early-stage therapy approaches, where the as yet inefficient drugs on which we had pinned our hopes may prove effective,” says Professor Klaus Gerwert from the Department of Biophysics at RUB.

In Alzheimer’s patients, the amyloid beta protein folds incorrectly due to pathological changes long before the first symptoms occur. A team of researchers headed by Klaus Gerwert successfully diagnosed this misfolding using a simple blood test; as a result, the disease can be detected approximately eight years before the first clinical symptoms occur. The test wasn’t suitable for clinical applications however: it did detect 71 per cent of Alzheimer’s cases in symptomless stages, but at the same time provided false positive diagnoses for nine per cent of the study participants. In order to increase the number of correctly identified Alzheimer’s cases and to reduce the number of false positive diagnoses, the researchers poured a lot of time and effort into optimising the test.

As a result, they have now introduced the two-tier diagnostic method. To this end, they use the original blood test to identify high-risk individuals. Subsequently, they add a dementia-specific biomarker, namely tau protein, to run further tests with those test participants whose Alzheimer’s diagnosis was positive in the first step. If both biomarkers show a positive result, there is a high likelihood of Alzheimer’s disease. “Through the combination of both analyses, 87 of 100 Alzheimer’s patients were correctly identified in our study,” summarises Klaus Gerwert. “And we reduced the number of false positive diagnoses in healthy subjects to 3 of 100. The second analysis is carried out in cerebrospinal fluid that is extracted from the spinal cord.

Now, new clinical studies with test participants in very early stages of the disease can be launched,” points out Gerwert. He is hoping that the existing therapeutic antibodies will still have an effect. “Recently, two major promising studies have failed, especially Crenezumab and Aducanumab – not least because it had probably already been too late by the time therapy was taken up. The new test opens up a new therapy window.”

Source: https://news.rub.de/

Air Pollution Harms Your Brain And Your Intelligence

Chronic exposure to air pollution can cause harm to cognitive performance, a new study reveals. Researchers believe that the negative impact increases with age, and affects men with less education the worst. Over four years, the maths and verbal skills of some 20,000 people in China were monitored by the US-Chinese study.  Scientists believe the results have global relevance, with more than 80% of the world’s urban population breathing unsafe levels of air pollution.

The study was based on measurements of sulphur dioxide, nitrogen dioxide and particulates smaller than 10 micrometres in diameter where participants lived. It is not clear how much each of these three pollutants is to blame. Carbon monoxide, ozone and larger particulates were not included in the study. Described as an invisible killer, air pollution causes an estimated seven million premature deaths a year worldwide, according to the World Health Organization.

We provide evidence that the effect of air pollution on verbal tests becomes more pronounced as people age, especially for men and the less educated,” the study published  in the Proceedings of the National Academy of Sciences (PNAS) said.

Pollution also increases the risk of degenerative diseases such as Alzheimer’s and other forms of dementia, the study suggests. Exposure to high levels of polluted aircan cause everyone to reduce their level of education by one year…, which is huge,” one of the co-authors, Xi Chen of the Yale School of Public Health, told.

Previous studies found air pollution had a negative impact on students’ cognitive abilities. In this study, researchers tested people of both sexes aged 10 and above between 2010 and 2014, with 24 standardised maths questions and 34 word-recognition questions.

Source: http://www.pnas.org/
AND
https://www.bbc.co.uk/