Tag: Alzheimer's disease

Categories : Genetics Neurodegenerative DiseasesTags :

Phase 1 Clinical Trial of a Gene Therapy for Alzheimer’s

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Image source: Pixabay/CC0

Researchers at University of California San Diego School of Medicine have received a grant to conduct a first-in-human Phase 1 clinical trial of a gene therapy for treating Alzheimer’s disease (AD) or Mild Cognitive Impairment (MCI), a condition often preceding dementia.

Gene therapy is an experimental technique that uses genes or gene products for the treatment or prevention of diseases by altering the DNA of living cells. Viral vectors are commonly used to insert the DNA changes into the target cells’ nuclei, but non-viral vectors also exist though they are generally less efficient.

The clinical trial, developed by principal investigator Mark Tuszynski, MD, PhD, professor of neuroscience and director of the Translational Neuroscience Institute at UC San Diego School of Medicine, delivers the brain-derived neurotrophic factor (BDNF) gene into the brains of qualifying trial participants where it is hoped it will stimulate BDNF production in cells.

BDNF belongs to a family of growth factors (proteins) found in the brain and central nervous system that support existing neurons and promote growth and differentiation of new neurons and synapses. BDNF is particularly important in brain regions susceptible to degeneration in AD.

“We found in earlier studies that delivering BDNF to the part of the brain that is affected earliest in Alzheimer’s disease — the entorhinal cortex and hippocampus — was able to reverse the loss of connections and to protect from ongoing cell degeneration,” said Tuszynski. “These benefits were observed in aged rats, aged monkeys and amyloid mice.”

The three-year-long trial seeks to recruit 12 participants with either diagnosed AD or MCI to receive AAV2-BDNF treatment, with another 12 persons serving as a control group over that period.

This will be the first safety and efficacy assessment of AAV2-BDNF in humans. A previous gene therapy trial from 2001 to 2012 using AAV2 and a different protein called nerve growth factor (NGF) found increased growth, axonal sprouting and activation of functional markers in the brains of participants.

“The BDNF gene therapy trial in AD represents an advance over the earlier NGF trial,” said Tuszynski. “BDNF is a more potent growth factor than NGF for neural circuits that degenerate in AD. In addition, new methods for delivering BDNF will more effectively deliver and distribute it into the entorhinal cortex and hippocampus.”

Source: UC San Diego

Categories : Ageing Diet and Nutrition Neurodegenerative DiseasesTags :

A Mediterranean Diet Keeps Dementia at Bay

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A dish full of vegetables which could be in a Mediterranean diet.

Researchers have reported that a Mediterranean diet may reduce the risk of developing dementia and cognitive loss, helping preserve memory functions as people age.

Specifically, the diet appears to lower the level of amyloid and tau proteins that are linked with dementia. People following the Mediterranean diet, already noted for its numerous health benefits, scored better on memory tests than those who were not following the diet.

The first of these proteins, amyloid protein, forms plaques in the brain, whereas the second, tau protein, forms tangles. Both are present in the brains of people with Alzheimer’s, though they are not uncommon in the brains of healthy older people, too.

“These results add to the body of evidence that shows what you eat may influence your memory skills later on,” said study author Tommaso Ballarini, PhD, of the German Center for Neurodegenerative Diseases in Bonn, Germany. He adds:

Studies have linked good health with the foods that people living in Greece, Spain, and Italy ate before the 1960s. This diet consists primarily of vegetables and fruits, nuts and seeds, legumes, potatoes, whole grain foods, seafood, extra virgin olive oil, and wine in moderation. Poultry, eggs and dairy products are present to a limited extent, while red meat, added sugar, refined grains and oils, and processed foods are typically lacking in a Mediterranean diet.

Kristin Kirkpatrick, a dietitian at Cleveland Clinic told Medical News Today that the contents of a Mediterranean diet offers beneficial “omega-3 fatty acids, polyphenols, specific minerals, fiber, and protein” that “may support the brain’s health and protection throughout the years.”

However, Kirkpatrick cautioned that, “A diet, even one with strong clinical data on its benefit, is only as healthy as the individuals who choose its structure.”

Sensible portion sizes are important, she noted and warned against the “consumption of processed foods that are marketed as heart-healthy or contain the components seen in a traditional Mediterranean approach.”

The investigators recruited 512 individuals from the German Centre for Neurodegenerative Diseases’ Longitudinal Cognitive Impairment and Dementia StudyTrusted Source. Participant  assessments showed that 343 were at a higher risk of developing Alzheimer’s disease while the other 169 people were “cognitively normal.”

Participants filled in questionnaires regarding the food they ate the previous month and the investigators asked them to record their intake of 148 specific food items. Participants were scored on their diet’s similarity to a Mediterranean diet, the most similar receiving a 9 and the least similar a 1. Since this was a self-reported study on eating habits, errors or misrepresentations are possible.

Individuals also took cognitive tests designed to detect the progression of Alzheimer’s disease. The tests assessed five areas: memory, working memory, language, executive functions, and visuospatial abilities. MRI brain scans determined each individual’s brain volume.

Finally, the researchers analyzed spinal fluid from a subsample of 226 participants who gave their consent, assessing the presence and amounts of the two biomarker proteins: amyloid and tau.

After adjusting for sex, age, and education, the scientists identified several clear links between better cognitive health and a Mediterranean diet.

The investigators  reported that:

  • Every dietary score point lower than 9 was linked to almost 1 year of the brain ageing that occurs in Alzheimer’s disease progression.
  • Participants who most closely followed the Mediterranean diet had fewer amyloid and tau protein biomarkers in their spinal fluid than those who had lower dietary scores.
  • People on the Mediterranean diet scored better on memory tests than people who were not.

Dr Ballarani concluded that, “More research is needed to show the mechanism by which a Mediterranean diet protects the brain from protein buildup and loss of brain function, but findings suggest that people may reduce their risk for developing Alzheimer’s by incorporating more elements of the Mediterranean diet into their daily diets.”

Source: Medical News Today

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 : 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

Categories : Neurodegenerative DiseasesTags :

Protein Synthesis Fix may Reverse Cognitive Decline in Alzheimer’s

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Restoring protein synthesis in the brain may reverse the cognitive decline associated with Alzheimer’s, according to a study by researchers from New York University (NYU) and the Federal University of Rio de Janeiro (UFRJ).

Current Alzheimer’s treatment research focuses on reducing the phenomena linked to the disease, such as amyloid plaques, neurofibrillary tangles, and neuroinflammation. The study aimed to determine whether restoring protein synthesis would also be beneficial.

“The synthesis of new proteins in the brain is essential for proper neuronal function and, notably, for memory consolidation. We and others have previously shown that impairments in brain protein synthesis contribute memory deficits in Alzheimer’s disease model mice, and that the brains of Alzheimer’s patients exhibit clear signs of impaired protein synthesis. We thus asked ourselves whether rescuing brain protein synthesis might be an approach to improve memory function in Alzheimer’s disease,” said co-senior author Sergio Ferreira, a professor at UFRJ.

“Given the complex nature of Alzheimer’s disease, identifying and targeting abnormal molecular pathways that effectively improve cognition has been challenging,” added co-senior author Eric Klann, a professor at NYU. “Our findings show that jump-starting protein synthesis in the brain can revive lost cognitive functions. We hope that this work can serve as a step forward in treating this devastating disease.”

Previous research found that a cellular quality control mechanism called the integrated stress response (ISR) was found to slow down protein synthesis to weed out problems like cancerous cells, but can get stuck in the ‘on’ position. In 2013, a drug called ISRIB was developed to reverse this (ISRIB stands for ISR InhiBitor). 

Previous research with ISRIB had shown positive results in restoring memory function in mice, months after traumatic brain injury (TBI), reversing cognitive impairments in Down Syndrome , preventing noise-related hearing loss, treating certain prostate cancers, and even cognitive enhancement in healthy animals.

The researchers determined that in Alzheimer’s patients, critical components of protein synthesis are depleted in the hippocampus. The researchers hypothesised that some cognitive function could be returned if protein synthesis was restored with ISRIB.  

The researchers used mice with Alzheimer’s-like conditions as a model. Testing the mice’s memory (eg with maze runs), they found memory function and hippocampal protein synthesis restored with ISRB. Restoration of hippocampal neural plasticity and memory functions was observed even in simulated advanced Alzheimer’s. 

The results indicate that restoring protein synthesis with drugs such as ISRIB, could work together towards reversing cognitive decline from Alzheimer’s in humans. 

Source: Medical Xpress

Journal information: “Correction of eIF2-dependent defects in brain protein synthesis, synaptic plasticity, and memory in mouse models of Alzheimer’s disease,” stke.sciencemag.org/lookup/doi … 26/scisignal.abc5429

Categories : Ageing Neurodegenerative DiseasesTags :

Obesity Adds to Alzheimer Severity

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In addition to it being a risk factor for many known chronic diseases, obesity is an additional burden on cerebral health and may also be associated with the progression of Alzheimer’s disease, according to a new study from the University of Sheffield and the University of Eastern Finland.  

The study used multimodal neural imaging and showed that obesity may contribute to the vulnerability of neural tissue, while maintaining a healthy weight helped to maintain brain structure in mid dementia Alzheimer’s disease.

Alzheimer’s disease is a neurodegenerative disease which accounts for two thirds of dementia in over 65s, is the sixth leading cause of death in the United States and there is no cure at present.  

Lead author Professor Annalena Venneri from the University of Sheffield’s Neuroscience Institute and NIHR Sheffield Biomedical Research Centre, said: “More than 50 million people are thought to be living with Alzheimer’s disease and despite decades of ground breaking studies and a huge global research effort we still don’t have a cure for this cruel disease.

“Prevention plays such an important role in the fight against the disease. It is important to stress this study does not show that obesity causes Alzheimer’s, but what it does show is that being overweight is an additional burden on brain health and it may exacerbate the disease.”

She added that it was important to educate people early on in their lives as it was too late to wait until the 60s to lose weight as the disease lurks in the backgrounds.

The researchers examined MRI scans of the brains of 47 patients diagnosed with mild Alzheimer’s disease dementia, 68 patients with mild cognitive impairment, and 57 individuals who were cognitively healthy. Using three complementary, computational techniques, they studied the brain’s anatomy, blood flow and also the brain’s fibres.

They compared gray matter volume, white matter integrity, cerebral blood flow and obesity. Grey matter volume decreases in Alzheimer’s. In patients with mild Alzheimer’s, an association was found with obesity and grey matter volume around the right temporoparietal junction, suggesting obesity creates a neural vulnerability in cognitively impaired patients. The study also found that maintaining a healthy weight may help preserve brain structure in structure in the presence of age and disease-related weight loss.

Joint author Dr Matteo De Marco from the University of Sheffield’s Neuroscience Institute, said: “Weight-loss is commonly one of the first symptoms in the early stages of Alzheimer’s disease as people forget to eat or begin to snack on easy-to-grab foods like biscuits or crisps, in place of more nutritional meals.

“We found that maintaining a healthy weight could help preserve brain structure in people who are already experiencing mild Alzheimer’s disease dementia. Unlike other diseases such as cardiovascular disease or diabetes, people don’t often think about the importance of nutrition in relation to neurological conditions, but these findings show it can help to preserve brain structure.”

Source: Medical Xpress

Journal information: Manmohi D. Dake et al, Obesity and Brain Vulnerability in Normal and Abnormal Aging: A Multimodal MRI Study, Journal of Alzheimer’s Disease Reports (2021). DOI: 10.3233/ADR-200267