Category: Neurodegenerative Diseases

Categories : Ageing Cardiovascular Disease Neurodegenerative DiseasesTags :

Mitochondria Dump DNA into Cells, Triggering Inflammation

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Researchers have discovered that when building blocks for DNA in cells are in short supply, mitochondria— the powerhouses of cells — release their own DNA, triggering an inflammatory response. Targeting this process can now open up new avenues of treatment into ageing-related diseases.

Mitochondria, the producers of energy for cells, , have their own genetic material: mitochondrial DNA. In certain situations, however, mitochondria are known to release their DNA into the interior of the cell, provoking a reaction from the cell’s own immune system. Some cardiac and neurodegenerative diseases as well as the ageing process are associated with the mitochondrial genome.

To find out when mitochondria release their DNA, the researchers have focused on the mitochondrial protein YME1L. “In cells lacking YME1L, we observed the release of mitochondrial DNA into the cell interior and a related immune response in the cells,” explained Thomas MacVicar, one of the study’s two first authors.  
“If the cells lack YME1L, there is a deficiency of DNA building blocks inside the cell,” he continued. “This deficiency triggers the release of mitochondrial DNA, which in turn causes an inflammatory response in the cell: the cell stimulates similar inflammatory reactions as it does during a bacterial or viral infection. If we add DNA building blocks to the cells from the outside, that also stops the inflammation.”

This newly discovered link between cellular inflammatory response and the metabolism of DNA building blocks could have far-reaching consequences, MacVicar explained. “Some viral inhibitors stop the production of certain DNA building blocks, thereby triggering an inflammatory response. The release of mitochondrial DNA could be a crucial factor in this, contributing to the effect of these inhibitors,” he said. 
Mitochondrial DNA is associated with a number of ageing-associated inflammatory diseases, including cardiac and neurodegenerative diseases, as well as obesity and cancer. The authors hope that new therapeutic opportunities in such diseases can be created by modulating the metabolism of DNA building blocks.

Source: Medical Xpress

Journal information: Hans-Georg Sprenger et al, Cellular pyrimidine imbalance triggers mitochondrial DNA–dependent innate immunity, Nature Metabolism (2021). DOI: 10.1038/s42255-021-00385-9

Categories : Neurodegenerative DiseasesTags :

Sleep Apnoea Treatment May Reduce Risk of Dementia

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Older adults receiving positive airway pressure therapy for obstructive sleep apnoea (OSA) may have a lower risk of developing Alzheimer’s disease and other kinds of dementia, according to a new study.

In a nationally representative study, Researchers from Michigan Medicine’s Sleep Disorders Centers analysed Medicare claims of over 50 000 Medicare beneficiaries 65 and older with OSA. They sought to find out whether people using positive airway pressure therapy had less risk of receiving a new diagnosis of dementia or mild cognitive impairment over the next 3 years, compared to those not using positive airway pressure therapy.

“We found a significant association between positive airway pressure use and lower risk of Alzheimer’s and other types of dementia over three years, suggesting that positive airway pressure may be protective against dementia risk in people with OSA,” said lead author Galit Levi Dunietz, PhD, MPH, an assistant professor of neurology and sleep epidemiologist.

The findings stress the impact of sleep on cognitive function. “If a causal pathway exists between OSA treatment and dementia risk, as our findings suggest, diagnosis and effective treatment of OSA could play a key role in the cognitive health of older adults,” said principal investigator Tiffany J. Braley, MD, MS, associate professor of neurology.

Obstructive sleep apnoea is a condition where there are episodes of complete or partial collapse of the airway with an associated decrease in oxygen saturation or arousal from sleep. This disturbance results in fragmented, nonrestorative sleep, and is associated with a variety of other neurological and cardiovascular conditions. Many older adults are at high risk for OSA. Dementia is prevalent as well, with roughly 5.8 million Americans currently living with it, said Prof Braley.

Source: Medical Xpress

Journal information: G L Dunietz et al, Obstructive Sleep Apnea Treatment and Dementia Risk in Older Adults, Sleep (2021). DOI: 10.1093/sleep/zsab076

Categories : Neurodegenerative DiseasesTags :

Exercise Slows Cognitive Decline in APOE4-related Parkinson’s Disease

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Results from a longitudinal study showed physical activity reduced  cognitive decline in early APOE4-related Parkinson’s disease.

Jin-Sun Jun, MD, of Hallym University in Seoul, and colleagues in Neurology presented the findings of a longitudinal study on a group of 173 recently diagnosed Parkinson’s patients. Of this group, those who with an apolipoprotein E ε4 (APOE4) allele had faster cognitive decline on the 30-point Montreal Cognitive Assessment (MoCA) scale than noncarriers (estimate -1.33, 95% CI -2.12 to -0.47, P=0.002). However, among the APOE4 carriers, higher physical activity was related to slower cognitive decline (estimate 0.007, 95% CI 0.003-0.011, P=0.001)..

Dr Jun noted that this reflects a number of studies that have demonstrated that Parkinson’s patients who exercise regularly show better clinical outcomes, including motor and cognitive function.

“These observations are supported by epidemiological data showing a link between physical activity and decreased risk for Parkinson’s disease,” Dr Jun told MedPage Today. “Because previous data indicate that physical activity modifies the APOE4 effect on the development and progression of Alzheimer’s disease, we hypothesized that physical activity also plays a role in modulating the association between APOE4 and cognition in Parkinson’s disease.”

Genetic factors interact with physical activity on other health outcomes, noted Jacob Raber, PhD, of Oregon Health and Science University in Portland, and colleagues, in an accompanying editorial.

“If similar gene-by-physical activity interactions were identified in Parkinson’s disease, they could pave the way for personalized treatment,” Raber and colleagues wrote. “While the effects of APOE4 on promoting beta-amyloid and tau pathology are well-established, recent studies show that APOE4 is also associated with more profound pathology of alpha-synuclein and higher measures of cognitive burden, both in mouse models and in humans with Parkinson’s disease.”

In their study, the researchers followed recently diagnosed patients in the Parkinson’s Progression Markers Initiative cohort who were not treated for Parkinson’s and who had abnormal dopamine transporter (DAT) imaging.

Self-reported physical activity was begun 2 years after enrollment and scored on the Physical Activity Scale of the Elderly. Cognitive function was measured annually with the MoCA, which is well-suited for Parkinson’s patients, and DAT imaging was performed at years 2 and 4. Assessments performed at years 2, 3, and 4 were used for analysis.

There was no significant interaction seen between physical activity and APOE4 involving change in striatal DAT activities. This suggests that striatal dopaminergic function may not be a major factor in physical activity’s protective effect on APOE4-related cognitive decline, Dr Jun and colleagues noted. “These negative results may be explained by the modest effect of APOE4 on the nigrostriatal dopaminergic system,” they wrote. “Furthermore, our follow-up duration may be too short to comprehend the impact of APOE4 on this system, considering the slow progressive nature of alpha-synucleinopathy.”

The researchers also pointed out that the exercise could offer benefits through mechanisms unrelated to the disease. “Although we cannot conclude what types or amounts of exercise help to slow progression from this study design, even non-high-intensity physical activity positively modified the impact of APOE4 on cognitive function,” Jun said.

The study’s limitations included physical activity being self-reported, cognitive function being based only on MoCA scores, and a short follow-up time. Though motor scores in the off-medication state were adjusted for, physical activity may have been less due to disease progression.

Source: MedPage Today

Categories : Neurodegenerative DiseasesTags :

Green Light for New Device for MS Treatment

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The American Food & Drug Administration has approved a new device for treating gait deficits in multiple sclerosis (MS) patients.

The Portable Neuromodulation Stimulator (PoNS), generates electrical pulses on the tongue to stimulate trigeminal and facial nerves to treat motor deficits. The FDA said that for it to be available by prescription, must be part of a supervised therapeutic exercise program in MS patients 22 and older. The device was authorised through the FDA’s ‘de novo’ premarket review pathway for new devices which pose do not pose significant risks of adverse effects.

In a statement, Christopher Loftus, MD, acting director of the Office of Neurological and Physical Medicine Devices in the FDA’s Center for Devices and Radiological Health, said: “MS is one of the most common neurological diseases in young adults. Today’s authorisation offers a valuable new aid in physical therapy and increases the value of additional therapies for those who live with MS on a daily basis.”

Onset of MS symptoms, which can include difficulties with walking and balance, typically occurs between 20 and 40, with greater frequency in women.

The PoNS device electrical stimulates the dorsal surface of the patient’s tongue. A control unit is worn around the neck which sends signals to a mouthpiece which the patient keeps in place with lips and teeth. Later, usage data can be viewed by a therapist to spot “potential areas of missed or shortened sessions,” the FDA noted.

The FDA gave their approval based on two clinical studies. One involved 20 MS patients with gait deficits (half with PoNS; half with a sham device). Th FDA said that the PoNS group showed “statistically significant and clinically significant” improvement in Dynamic Gait Index (DGI) scores at 14 weeks not seen in the sham device group.

The other study, with 14 patients, showed improvements from baseline in sensory organisation task scores (but not in DGI scores) at 14 weeks. There were no serious safety or adverse effects reported.

Among the FDA’s cautions, the FDA stated that the PoNS device should not be used by patients with penetrating brain injuries, neurodegenerative diseases, oral health problems, chronic infectious diseases, unmanaged hypertension or diabetes, pacemakers, or a history of seizures.

Source: MedPage Today

Categories : Lab Tests and Imaging Neurodegenerative DiseasesTags :

A Non-invasive Parkinson’s Test Inspired by Scent

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A  skin swab test has been developed for Parkinson’s disease, based on biomarker analysis of sebum, the oils that protect the skin – and it has a surprising inspiration. 

This comes about after the remarkable discovery of a woman’s ability to detect a certain smell in people who had the disease. 

Joy Milne, a retired nurse, noticed a “musky” scent on her husband years before he was diagnosed with Parkinson’s disease. A series of tests showed that she could detect the presence of Parkinson’s disease in people with 100% based on smell alone, prompting research which isolated the compounds she was smelling: higher concentrations of hippuric acid, eicosane, and octadecanal.

In order to exploit these biomarkers, researchers developed a mass spectrometry test to pick up their levels in sebum obtained with skin swabs. This has proved to be around 80% accurate.

Prof Perdita Barran said: “We believe that our results are an extremely encouraging step towards tests that could be used to help diagnose and monitor Parkinson’s.

“Not only is the test quick, simple and painless but it should also be extremely cost-effective because it uses existing technology that is already widely available.

“We are now looking to take our findings forwards to refine the test to improve accuracy even further and to take steps towards making this a test that can be used in the NHS and to develop more precise diagnostics and better treatment for this debilitating condition.”

This new test with its high reliability could help the diagnosis of Parkinson’s disease, which can be easily missed, especially in the early stages.
Daxa Kalayci, 56, was misdiagnosed several times over four years before finally finding out she had Parkinson’s in 2019.

“I was misdiagnosed with anxiety, stress-related tremors and told that my problems stemmed from going through the menopause,” she said.

“Despite my diagnosis eventually being confirmed… a quick and simple diagnostic test for Parkinson’s would have given me the chance to start my treatment earlier and enjoy life a lot more.

“But instead, I lost so many years not being able to pursue a career as a paramedic or go back to nursing.

“This test could be a game-changer for people living with Parkinson’s and searching for answers, like I was.”

Source: BBC News

Categories : Exercise Neurodegenerative DiseasesTags :

Golf Shines as Physical Activity for Parkinson’s Patients

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Putter and golf balls on golf course. Photo by Robert Ruggiero on Unsplash.

In a study comparing physical activity routine for Parkinson’s patients, golf produced greater improvements than tai chi. 

Previous studies had shown that tai chi practice was beneficial as physical activity for Parkinson’s patients, resulting in balance and mobility gains, and is also safe and popular with patients.

“We know that people with Parkinson’s disease benefit from exercise, but not enough people with the disease get enough exercise as therapy,” said study author Anne-Marie A. Wills, MD, of Massachusetts General Hospital Boston. “Golf is popular—the most popular sport for people over the age of 55—which might encourage people to try it and stick with it. We decided to compare golf to tai chi in our study because tai chi is the gold standard for balance and preventing falls in people with Parkinson’s.”

The study involved 20 people with moderate Parkinson’s disease, who were offered 10 weeks of two one-hour group classes a week, randomly assigned to either golf or tai chi.

Researchers evaluated everyone with tests, including ones for mobility. For the test, a person is timed while getting up from a chair, walking 3m and then returning to the chair and sitting down. Golfers were 0.96 seconds faster on the test at the end of the study.

“While the results for golf might be surprising, it’s important to remember that the number of participants in our study was small, and the period over which we studied them was relatively short,” Dr Wills said. “More research in larger groups of people, over longer periods of time, is needed.”

While overall satisfaction was similar in both groups, 86% of golfers compared to 33% of tai chi participants were “definitely” likely to continue the activity.

“Our finding that golfers were much more likely to continue with their sport is exciting because it doesn’t matter how beneficial an exercise is on paper if you people don’t actually do it,” Dr Wills said. “So if swinging a golf club is more appealing than practicing tai chi, by all means, go to a driving range and hit balls for an hour instead!”

Source: Medical Xpress

Categories : Ethics and Law Neurodegenerative DiseasesTags :

Man With Motor Neuron Disease Presents His Case for Euthanasia

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At a hearing, a man with a deteriorating condition from motor neuron disease (MND), laid out why he wants the right to choose patient-assisted suicide.

Diethelm Harck, 71, is seeking a change in the laws surrounding euthanasia in South Africa. He is presenting his case alongside Dr Suzanne Walter, a palliative care specialist who has multiple myeloma. Both may not live long enough to see the outcome of their application, and have set up trust funds to assist the overturning of laws surround euthanasia and patient-assisted suicide in South Africa.

In his evidence, he said that he loves life “but my biggest fear is that when my love of life reaches the stage of fearing life, I will not be able to die.”

In the hearing via Zoom, Mr Harck said that he used to exercise daily but now takes three hours to complete a simple routine like getting up and making breakfast.Mr Harck said that his deterioration would be progressive; his muscles are weakening eventually he will be unable to breathe as his diaphragm will stop working.

“From what I have seen and witnessed, MND death is not peaceful,” he said. “I have seen a number of colleagues and [support] group members pass away. They had no way to communicate. And they could not breathe easily.”

Mr Harck continued, “We once visited a young girl suffering from MND, who was totally paralysed. She could only speak with the help of an eye gaze machine. When Lynn [Mr Harck’s life partner] asked her what she feared the most, she said not being able to die.”

Their application is being opposed by The Health Professions Council of South Africa and the Ministers of Health, Justice and the National Director of Public Prosecutions. They claimed that palliative care was available to most South Africans and that the right to life must be protected by the ban on euthanasia.

Source: Eyewitness News

Categories : Environmental Effects Neurodegenerative DiseasesTags :

With Climate Change, Heat May Worsen Multiple Sclerosis Symptoms

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As average global temperatures increase due to climate change, multiple sclerosis (MS) patients can experience worsening symptoms resulting in an increase in hospital visits.

Some 60% to 80% of MS patients experience heat sensitivity. Increased body temperature slows or stops nerve signals in damaged nerves, which has a number of impacts such as blurred vision and other neurological effects. Heat sensitivity is also correlated with fatigue. Together with fatigue, divided attention from heat sensitivity can contribute to falls.

“We know that heat sensitivity is common in multiple sclerosis, and climate scientists expect that periods of anomalously warm weather will become more frequent with climate change,” said study author Holly Elser, PhD. of Stanford University School of Medicine. “Our study suggests that warming trends could have serious health implications over the long term for people living with MS.”

The study defined anomalously warm weather as a month in which local average temperatures were higher than the long-term average temperature for that month by at least 1.5C.

The researchers drew data on insurance claims for 106 225 people with MS living in the US, and then calculated the estimated effect of anomalously warm weather on MS-related emergency department, inpatient and outpatient visits. Then, the number of medical visits for each person during anomalously warm weather periods was compared to those for periods of normal weather periods.

During anomalously warm weather periods, there was a 4% increased chance of an emergency department visit compared to periods of normal weather. Participants had a 3% increased chance of having an inpatient visit and a 1% increased chance of having an outpatient visit during anomalously warm periods compared to periods of normal weather.

Researchers estimate that during the follow-up period, anomalously warm weather periods were linked to an estimated excess of at least 592 emergency department visits, 1260 inpatient visits and 1960 outpatient visits related to MS.

“While the relative increase in risk of visits is small, the associated absolute effect on people with MS and the health care system is meaningful,” concluded Dr Elser.

Source: Medical Xpress

Categories : Medical Research & Technology Neurodegenerative DiseasesTags :

Scientists Develop AI Tool to Detect Parkinson’s Disease

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Researchers have developed an AI program that can assist physicians in performing a quantitative analysis when diagnosing Parkinson’s disease. 

As human populations continue to age due to improved medical care, there is an impending ‘Parkinson’s disease pandemic’ where numbers of individuals suffering this age-related neurodegenerative disease threaten to overwhelm healthcare systems. There is a need to distinguish between Parkinson’s and other diseases which have similar motor symptoms.
Assistant Professor Andrey Somov at the Skolkovo Institute of Science and Technology and colleagues developed a machine learning algorithm to analyse video recordings of patients performing certain tasks.

“As part of the research process, we had the opportunity to closely interact with doctors and medical personnel, who shared their ideas and experience. It was fascinating observing how two seemingly different disciplines came together to help people. We also had the opportunity to monitor all parts of the research, from designing the methodology to data analysis and machine learning,” Kovalenko said.

The advantages of the video analysis approach is that it is simple, objective, noninvasive, quick, inexpensive and versatile.

To develop the machine learning algorithm, the researchers recorded 83 patients with and without Parkinson’s performing 15 tasks that they had designed, such as filling a glass with water. These tasks were developed in a prior feasibility study using wearable sensors. The machine learning technology allows for objective analysis which picks up certain features of the disease which may not be visible to the naked eye.

Coauthor of the study Sklotech Assistant Professor Dmitry Dylov, and “Machine learning and computer vision methods we used in this research are already well established in a number of medical applications; they can be trusted, and the diagnostic exercises for Parkinson’s disease have been in development by neurologists for some time. What is truly new about this study is our quantitative ranking of these exercises according to their contribution to a precise and specific final diagnosis. This could only be achieved in collaboration between doctors, mathematicians and engineers.”

“This collaboration between doctors and scientists in data analysis allows for many important clinical nuances and details that help achieve the best results. We as doctors see great potential in this; apart from differential diagnosis, we need objective tools to assess motor fluctuation in patients with PD. These tools can provide a more personalized approach to therapy and help make decisions on neurosurgical interventions as well as assess the outcomes of surgery later,” noted coauthor of the paper, neurologist Ekaterina Bril.

Source: News-Medical.Net

Journal information: Kovalenko, E., et al. (2021) Distinguishing Between Parkinson’s Disease and Essential Tremor Through Video Analytics Using Machine Learning: a Pilot Study. IEEE Sensors.doi.org/10.1109/JSEN.2020.3035240.

Categories : Ageing General Interest Neurodegenerative DiseasesTags :

Legendary Singer Tony Bennett Diagnosed with Alzheimer’s

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Music legend Tony Bennett, 94, revealed in an interview that he was diagnosed with Alzheimer’s disease 4 years ago.

The singer’s career has spanned seven decades, he had continued his initial success in the 1950s across multiple genres, becoming a hit with the MTv generation, and in more recent years collaborating with popular artists like Amy Winehouse and Lady Gaga.

Alzheimer’s disease is an age-related, irreversible neurodegenerative condition. In more than 90% of patients, it begins after age 65, although it can occur as early as in the 30s. It is marked by memory loss and confusion that seem like the normal cognitive decline of older age, but it is more rapid and severe, eventually resulting in death. As people live longer and the risks of developing this disease increase with age, the burden of this disease is expected to increase in the future. In the US, the number of people with Alzheimer’s is expected to nearly triple from 5.5 million to 14 million by 2060.

Mr Bennett has been able to work over the past four years but the toll is perceptible. He still recognises his family members but his short-term and long-term memory have drastically deteriorated. Interviewer John Colapinto noted Mr Bennett gazing at his lavishly illustrated book, “Tony Bennett Onstage and in the Studio” (2018). “He stared into its pages not with the air of warm reminiscence but like a man struggling to recall why these images seemed familiar.” His wife, Susan, added that Mr Bennett is “not always sure where he is or what is happening around him. Mundane objects as familiar as a fork or a set of house keys can be utterly mysterious to him.”

Over the past two years, Mr Bennett recorded a second album of duets with Lady Gaga, a follow-up to the hit album with Gaga in 2014. While he had been known to be a “meticulous and hard-driving perfectionist in the studio,” Mr Bennett was much more subdued. speaking rarely, his words coming haltingly and seeming lost or bewildered. Gaga, who considers Mr Bennett to be “an incredible mentor, and friend, and father figure” is seen breaking down in tears as Tony sings a solo passage of a love song.

The album is due to be released this spring, but Mr Bennett will be unable to do promotional interviews. Mr Bennett, together with his wife and son (who is also his manager) decided to break the news, in the hopes that as many fans as possible know about what will likely be his final record. The neurologist who diagnosed Bennett in 2016,  Gayatri Devi, MD, said: “He is doing so many things, at 94, that many people without dementia cannot do. He really is the symbol of hope for someone with a cognitive disorder.”

Source: MedPage Today