Yearly Archives: 2017

A new study to compare key outcomes in care homes that implemented an individualized music program called MUSIC & MEMORY with similar homes that did not adopt the program found that after homes adopted the program, residents with dementia became significantly more likely to discontinue antipsychotic and antianxiety medications and significantly less likely to engage in disruptive behaviors, compared to those residing in homes used for comparison.

The study of more than 25,000 residents in 196 nursing homes in the United States was published in The American Journal of Geriatric Psychiatry.

The study’s findings reinforce personal reports among caregivers and family members, including those presented in the documentary “Alive Inside,” suggesting that personalized music helps patients even when their dementia is highly advanced.

To better understand how widespread such effects may be and how they might become clinically meaningful, the researchers designed a new evaluation to test the program’s effects with greater national breadth and statistical rigor than previous study designs.

To make their comparison, the team identified 98 nursing homes that had received formal training in the MUSIC & MEMORY program during 2013 and then assembled a list of similar nursing homes — accounting for Medicare quality rating, geography, the age mix of residents and other factors — that did not implement the program. The researchers included in the study all residents in each kind of home who had dementia and cognitive impairment, but who were not receiving hospice care and were not comatose. In all, 12,905 such residents lived in program homes, while 12,811 residents lived in non-program homes.

Using federal Medicare and nursing home data, the researchers then compared the before-2013-and-after changes among residents in each group on four metrics: ending antipsychotic medication, ending antianxiety medication, reductions in disruptive behavior and improvement in mood. While there were no significant differences in mood, after MUSIC & MEMORY implementation in program homes they found reductions in the use of antipsychotic and antianxiety medications as well as reductions in behavior problems.

The researchers caution that since they did not track everything each nursing home might be doing to achieve these care improvements, they can’t be sure that all the improvements resulted from MUSIC & MEMORY specifically.

To improve their evaluation, the researchers plan to conduct a second study in which they will randomize some homes to implement the program and some comparison homes to continue without it.

Paper: “Individualized Music Program is Associated with Improved Outcomes for U.S. Nursing Home Residents with Dementia”
Reprinted from materials provided by Brown University.

Recent research on Parkinson’s disease has focused on the gut-brain connection, examining patients’ gut bacteria, and even how severing the vagus nerve connecting the stomach and brain might protect some people from the debilitating disease.

But scientists understand little about what’s happening in the gut — the ingestion of environmental toxins or germs, perhaps — that leads to brain damage and the hallmarks of Parkinson’s such as tremors, stiffness and trouble walking.

Now researchers have identified a potential new mechanism in both mice and human endocrine cells that populate the small intestines. Inside these cells is a protein called alpha-synuclein, which is known to go awry and lead to damaging clumps in the brains of Parkinson’s patients, as well as those with Alzheimer’s disease.

The study was published in JCI Insight.

The researchers hypothesized that an agent in the gut might interfere with alpha-synuclein in gut endocrine cells, deforming the protein. The deformed or misfolded protein might then spread via the nervous system to the brain as a prion.

But how would a protein go from traveling through the inner-most ‘tube’ of the intestine, where there are no nerve cells, into the nervous system? In a 2015 study, the same researchers showed that although the main function of gut endocrine cells is to regulate digestion, these cells also have nerve-like properties.

Rather than using hormones to communicate indirectly with the nervous system, these gut endocrine cells physically connect to nerves, providing a pathway to communicate directly with the nervous system and brain.

With the new finding of alpha-synuclein in endocrine cells, the researchers now have a working explanation of how malformed proteins can spread from the inside of the intestines to the nervous system, using a non-nerve cell that acts like a nerve.

The researchers plan to gather and examine the gut endocrine cells from people with Parkinson’s to see if they contain misfolded or otherwise abnormal alpha-synuclein. New clues about this protein could help scientists develop a biomarker that could diagnose Parkinson’s disease earlier.

New leads on alpha-synuclein could also aid the development of therapies targeting the protein.

Paper: “α-Synuclein in gut endocrine cells and its implications for Parkinson’s disease”
Reprinted from materials provided by Duke University Medical Center.

A new study has uncovered a molecular mechanism in the prion protein, a protein responsible for neurodegenerative diseases, which may explain why nerve cells degenerate in these disorders. The findings appear in the journal eLife.

The prion protein plays a crucial role in fatal neurodegenerative disorders like Creutzfeldt-Jakob disease in humans and « mad cow disease » in cattle. Prion diseases are part of a larger group of human neurodegenerative disorders, including Alzheimer’s, Parkinson’s and Huntington’s diseases, which are all due to the abnormal accumulation of protein aggregates in the brain.

Using a multi-disciplinary approach involving electrophysiological, cellular and biophysical techniques, the researchers found that parts of the prion protein produced abnormal electrical currents in cells. Antibodies that interfered with functioning did the same. Importantly, the antibody treatment also caused severe degeneration of nerve cell dendrites, the regions that are essential for normal communication between nerve cells. The researchers applied a sophisticated chemical technique to demonstrate that the two ends of the prion protein interact with each to alter the amount of toxic signal that is delivered.

As a result of their findings, the researchers caution against administering antibodies against the prion protein as a possible therapy for both prion and Alzheimer’s diseases.

Paper: “The N-terminus of the prion protein is a toxic effector regulated by the C-terminus”
Reprinted from materials provided by Boston University Medical Center.

New research shows that the APP gene variant protecting against Alzheimer’s disease significantly decreases plasma beta-amyloid levels in a population cohort. This is a significant discovery because many ongoing drug trials in the field of Alzheimer’s disease focus on decreasing beta-amyloid levels in the brain tissue. According to the study, a 30% life-long decrease in beta-amyloid levels is not associated with detrimental effects on lipid or glucose metabolism, or on any other metabolic factors.

The findings were published in Annals of Neurology.

Alzheimer’s disease is a neurodegenerative disease strongly characterised by the accumulation of beta-amyloid in the brain tissue. Uncovering the genetic pathogenesis of Alzheimer’s disease has been a target of great interest over the past few years, and genome-wide mapping studies focusing on risk genes have led to significant advances in the field. These studies have identified not only several new risk genes for Alzheimer’s disease, but also gene variants that protect against it.

Research groups focusing on Alzheimer’s disease and diabetes have now shown that the APP A673T gene variant, which is a variant in the amyloid precursor protein gene protecting against Alzheimer’s disease, leads to an average of 30 per cent decreased levels of the beta-amyloid subtypes 40 and 42. The effects of this previously discovered gene variant were analysed by utilising data from the unique and extensive METSIM study, which comprises 10,000 men living in the eastern part of Finland. Approximately 0.3% of the population are carriers of the APP A673T gene variant.

The findings on the role of the APP A673T gene variant in Alzheimer’s disease facilitate the planning of future research. This insight, in turn, could enable the identification of new drug targets, increasingly good predictive biomarkers and the development of personalised medical applications.

Paper: “Decreased plasma β-amyloid in the Alzheimer’s disease APP A673T variant carriers”
Reprinted from materials provided by University of Eastern Finland.

A team of researchers is using breakthrough gene-editing technology to develop a new screening tool for Parkinson’s disease. The technology allows scientists in the lab to “light up” and then monitor alpha-synuclein, a brain protein that has been associated with Parkinson’s. The study was published in Scientific Reports.

The researchers used CRISPR Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats) gene-editing technology. The system is one of research’s fastest growing biomedical techniques that allows scientists to make specific changes in the DNA of plants and animals while not killing cells. The system is becoming instrumental in studying genetically based treatments for diseases including cancer and Parkinson’s.

Using the CRISPR technique, the team edited the alpha-synuclein gene and inserted a luminescent tag made from the same proteins that cause fireflies to light up. Every time the cell creates the alpha-synuclein protein, the tag gives off a light. The team found that measuring the light was a reliable method to measure alpha-synuclein production.

With the engineered cells, researchers can screen new and existing drugs to see how they regulate alpha-synuclein level in patients. The scientists hope to go on to identify ways to reduce alpha-synuclein production that can possibly prevent Parkinson’s or its progression in patients diagnosed with the disease.

Paper: “A novel tool for monitoring endogenous alpha-synuclein transcription by NanoLuciferase tag insertion at the 3′end using CRISPR-Cas9 genome editing technique”
Reprinted from materials provided by University of Central Florida.

A study has found that abnormal proteins found in Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease all share a similar ability to cause damage when they invade brain cells.

The finding potentially could explain the mechanism by which Alzheimer’s, Parkinson’s, Huntington’s, and other neurodegenerative diseases spread within the brain and disrupt normal brain functions. The study was published in Acta Neuropathologica.

Previous research has suggested that in all three diseases, proteins that are folded abnormally form clumps inside brain cells. These clumps spread from cell to cell, eventually leading to cell deaths. Different proteins are implicated in each disease: tau in Alzheimer’s, alpha-synuclein in Parkinson’s and huntingtin in Huntington’s disease.

The researchers focused on how these misfolded protein clumps invade a healthy brain cell. The authors observed that once proteins get inside the cell, they enter vesicles (small compartments that are encased in membranes). The proteins damage or rupture the vesicle membranes, allowing the proteins to then invade the cytoplasm and cause additional dysfunction.

The researchers said the finding that protein clumps associated with the three diseases cause the same type of vesicle damage was unexpected. The researchers, who are based in the U.S., initially focused on alpha-synuclein proteins associated with Parkinson’s disease. They asked a French collaborator known for his ability to generate distinct types of alpha-synuclein to send them different types. Without telling the researchers, the collaborator sent other types of proteins as well. This led to the surprise finding that tau and huntingtin proteins also can damage vesicles.

Paper: “Endocytic vesicle rupture is a conserved mechanism of cellular invasion by amyloid proteins”
Reprinted from materials provided by Loyola University Health System.

A new study heightens concerns over the detrimental short- and long-term impact of airborne iron-rich strongly magnetic combustion-derived nanoparticles (CDNPs) present in dogs and young urbanites’ brains. Using transmission electron microscopy, the researchers documented by abundant combustion nanoparticles in neurons, glial cells, choroid plexus, and neurovascular units of Mexico City dogs, children, teens and young adults chronically exposed to concentrations above the US-EPA standards for fine particulate matter. These findings were published in the Journal of Alzheimer’s Disease.

The detrimental impact of these tiny particles getting into the brain through the nasal and olfactory epithelium, the lungs and the gastrointestinal system is quickly recognized by extensive alterations in critical neuronal organelles including mitochondria, as well as axons and dendrites. Since these nanoparticles are in close contact with neurofilaments, glial fibers and chromatin, the researchers are very concerned about their potential for altering microtubule dynamics, accumulation and aggregation of unfolded proteins, mitochondrial dysfunction, altered calcium homeostasis and insulin signaling, and epigenetic changes.

These particles are ubiquitous and present in high concentrations in children as young as 3 years old. The particles contain transition neurotoxic metals and they are causing extensive brain damage in key organelles. It is now necessary to explore the potential impact of these particles in brain neurodegeneration.

Paper: “Combustion-Derived Nanoparticles in Key Brain Target Cells and Organelles in Young Urbanites: Culprit Hidden in Plain Sight in Alzheimer’s Disease Development”
Reprinted from materials provided by IOS Press.