Study Underway For a New Drug to Reduce Alzheimer's Effect

From July 22nd to July 26th, 2018, the Alzheimer’s Association International Conference was held in Chicago, Illinois. Of the numerous presentations made during the Conference, one stood out as a possible medical breakthrough. According to NeuroActiva Inc., a company based out of California, research is being conducted on a drug called NA-831, which is aimed at reducing mild cognitive deterioration, associated with Alzheimer's disease.

The study was conducted by researchers of NeuroActiva Inc., in collaboration with the Florey Institute of Neuroscience and Mental Health in Australia, an affiliation of the University of Melbourne and Austin Hospital.

The Clinical Trial was carried out as a double-blind placebo-controlled study on the safety and efficacy of the drug NA 831. This essentially means that none out of the final 56 participants chosen (out of nearly 150 that enrolled to participate in the trial) had knowledge of whether they were receiving the placebo or the drug, and the distribution of the same was completely randomized.

Finally, the chosen 56 participants were randomly given either the placebo or 10 mg of NA-381, to be consumed strictly daily for a period of 24 weeks. According to Mr. Lloyd L. Tran, the Chairman and CEO of NeuroActiva Inc., the drug NA-831 was designed specifically to target neurotransmitters in the brain, with the aim of reconnecting them.

The first phase of the trial hoped that by revitalizing the communication system of the brain, both memory and functionality could be restored and improved. The main focus of the trial was reversing or lessening the effects of mild cognitive impairment (MCI), which is also defined as the “symptomatic pre-dementia stage” of the cognitive decline associated with Alzheimer’s. The first phase of the test, therefore, targeted specifically those with MCI rather than existing and prevalent dementia.

The Clinical Trial used two major scales to measure the outcomes of the study. These are :
1) Clinical Dementia Rating scale-Sum of Boxes (CDR-SB) Score, which deals with 6 areas of cognitive function, namely memory, judgment and problem solving, orientation, home and hobbies, community affairs, and finally personal care.

2) Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (Mild Cognitive Impairment version) (ADCS-ADL MCI), which made use of the Galasko method for the study, that covered 23 different areas of self-care, mental and physical functioning.

Both scales of each patient were determined in Week 2 and Week 24 respectively, after the required dosage of either NA-831 or the placebo was taken. The results were obtained through a series of interviews and activities directed at the concerned patient as well as their loved ones. Per the results of these interviews and activities, the outcome of each patient was noted down in a 5 point scale for CDR-SB and a scoring range of 0-78 for ADCS-ADL, depending on the level of impairment.

After comparing the scores of the scales collected in Week 2 and the scores collected in Week 24, it was determined that there were improvements in numerous existing symptoms of Alzheimer’s, including but not limited to fatigue, irritability, and rectified sleep patterns along with slowly improved cognitive functioning. 

In the next steps of the trial, the dose of NA-831 taken by patients was increased to 20 mg and then 40 mg. It was found that up to 50 mg of the drug could be taken and easily tolerated on daily basis by patients, with little to no side effects, with only 4 patients complaining of minor headaches and diarrhea.     

It has, however, been noted that the study did not comprehensively compare the results of the placebo and that of the drug NA-831, in a statistical manner. This makes it difficult to determine conclusively the effects of the drug on cognitive function in patients with either MCI or those suffering from moderate dementia, as a result of Alzheimer’s disease. 

As the drug currently remains in the testing and trial phase, it has not been conclusively proven that NA-831 will prevent cognitive damage, nor has any health authority been in a capacity to approve manufacture or sale of the drug on a wide-scale. Nonetheless, NA-831 has opened new doors in medicine to approach Alzheimer’s treatments from a different and powerful perspective.  

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14 drinks a week may put older adults at dementia risk

If you drink nearly 14 drinks per week (2 drinks per day) and already suffer from mild cognitive impairment (MCI), you may be at a higher risk of developing dementia than those who enjoy drink a week, say researchers. 

According to researchers from Harvard, among those adults with MCI, the risk of dementia according to numbers of alcoholic drinks per week wasn't statistically significant, although it appeared to be highest for drinking more than 14 drinks per week compared with less than one drink. 

In this cohort study of 3,021 participants aged 72 years and older, alcohol intake within recommended limits was not significantly associated with a lower risk of dementia among participants with or without mild cognitive impairment at baseline.
Among participants without mild cognitive impairment, daily low-quantity drinking was associated with lower dementia risk compared with infrequent higher-quantity drinking.
"The findings suggest that physicians caring for older adults need to carefully assess the full dimensions of drinking behaviour and cognition when providing guidance to patients about their alcohol consumption," said the researcher.

The study analyzed 3,021 adults (72 and older) who were free of dementia (2,548 were without MCI and 473 with MCI). During about six years of follow-up, there were 512 cases of dementia, including 348 cases of Alzheimer disease.
Among those adults without MCI, no amount of alcohol consumption was significantly associated with higher risk for dementia compared with drinking less than one drink per week.
Given the rapidly growing burden of Alzheimer disease (AD) and other dementia, including 50 million people currently living with dementia and 82 million expected by 2030, the identification of factors that prevent or delay the onset of dementia remains of paramount concern.

During the study, the participants reported their frequency of beer, wine, and liquor consumption in days per week and their usual number of 12-oz cans or bottles of beer, 6-oz glasses of wine, and shots of liquor consumed on each occasion.

"We categorized participants according to their alcohol consumption as follows: none, less than 1 drink per week, 1 to 7 drinks per week, 7.1 to 14 drinks per week, and more than 14 drinks per week," the authors wrote.

In this study of older adults, the association of self-reported alcohol consumption with dementia risk appeared to cluster into 3 separate dimensions—baseline cognition, dose and pattern.

"At present, our findings cannot be directly translated into clinical recommendations, and these findings warrant additional studies to confirm these associations further," the authors suggested. 

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Can a saliva test advance Alzheimer's disease diagnosis?

Scientists have identified biomarkers that can help in early detection of mild cognitive impairment and Alzheimer's disease in saliva samples. A saliva test would prove useful in clinical settings for its ease and non-invasive nature. It also has the potential to detect neurodegenerative diseases earlier on, allowing for early intervention, said a team of researchers.

Researchers examined saliva samples from three sets of patients - those with Alzheimer's disease, those with mild cognitive impairment and those with normal cognition. 

Using a powerful mass spectrometer, the team examined more than 6,000 metabolites - compounds that are part of our body's metabolic processes - to identify any changes or signatures between groups. "In this analysis, we found three metabolites that can be used to differentiate between these three groups," said a researcher.

"This is preliminary work because we've used a very small sample size. But the results are very promising. If we can use a larger set of samples, we can validate our findings and develop a saliva test of Alzheimer's disease," he noted. In addition, identifying these biomarkers is the ability to conduct efficacy testing for treatments. 

"Using the biomarkers we can also do testing to see what types of treatments are most effective in treating Alzheimer's disease, from diet to physical activity to pharmaceuticals," he added.

"So far, no disease-altering interventions for Alzheimer's disease have been successful," said a Prof. "For this reason, researchers are aiming to discover the earliest signals of the disease so that prevention protocols can be implemented."

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MRI brain scans can predict MRI dementia risk before symptoms appear

MRI brain scans can help predict whether a person will develop dementia in the next three years, before the symptoms of the disorder appear, scientists have found. In a study, researchers  used magnetic resonance imaging (MRI) brain scans to predict dementia with 89 per cent accuracy.
 
The findings suggest that doctors may one day be able to use widely available tests to tell people their risk of developing dementia before symptoms arise.

"Right now it's hard to say whether an older person with normal cognition or mild cognitive impairment is likely to develop dementia," said  an assistant professor.

"We showed that a single MRI scan can predict dementia on average 2.6 years before memory loss is clinically detectable, which could help doctors advise and care for their patients," said the Prof.

Although there are no drugs available yet to prevent or delay the onset of Alzheimer's disease, identifying those at high risk of developing dementia within the next few years could still be beneficial, the researchers said. People could make decisions on their financial and living arrangements while they are still in full control of their faculties.

Researchers analysed MRI scans for physical signs of impending cognitive decline. They used a technique called diffusion tensor imaging to assess the health of the brain's white matter, which encompasses the cables that enable different parts of the brain to talk to one another.

"Diffusion tensor imaging is a way of measuring the movement of water molecules along white matter tracts," the Prof. said.

"If water molecules are not moving normally it suggests underlying damage to white tracts that can underlie problems with cognition," he said.

Using information from the Alzheimer's Disease Neuroimaging Initiative -- a multisite collaboration that pools data, funding and expertise to improve clinical trials for Alzheimer's disease -- researchers identified 10 people whose cognitive skills declined over a two-year period and matched them by age and sex with 10 people whose thinking skills held steady.

The average age of people in both groups was 73. Then, the researchers analysed diffusion tensor MRI scans taken just before the two-year period for all 20 people. The researchers found that people who went on to experience cognitive decline had significantly more signs of damage to their white matter.

The researchers repeated their analysis in a separate sample of 61 people, using a more refined measure of white matter integrity. With this new analysis, they were able to predict cognitive decline with 89 per cent accuracy when looking at the whole brain. When the researchers focused on specific parts of the brain most likely to show damage, the accuracy rose to 95 per cent.

"We could tell that the individuals who went on to develop dementia have these differences on diffusion MRI, compared with scans of cognitively normal people whose memory and thinking skills remained intact,"the Prof. said. 

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Artificial intelligence technique recognizes signs of dementia two years before onset

Imagine if doctors could determine, many years in advance, who is likely to develop dementia.
Such prognostic capabilities would give patients and their families time to plan and manage treatment and care. Thanks to artificial intelligence research conducted recently, this kind of predictive power could soon be available to clinicians everywhere.

Scientists  used artificial intelligence techniques and big data to develop an algorithm capable of recognizing the signatures of dementia two years before its onset, using a single amyloid PET scan of the brain of patients at risk of developing Alzheimer's disease. 
 
A co-author of the study and Associate Professor of Neurology & Neurosurgery and Psychiatry, expects that this technology will change the way physicians manage patients and greatly accelerate treatment research into Alzheimer's disease.

By using this tool, clinical trials could focus only on individuals with a higher likelihood of progressing to dementia within the time frame of the study. This will greatly reduce the cost and the time necessary to conduct these studies". The Co-Author said

Amyloid as a biomarker of dementia

Scientists have long known that a protein known as amyloid accumulates in the brain of patients with mild cognitive impairment (MCI), a condition that often leads to dementia.

Though the accumulation of amyloid begins decades before the symptoms of dementia occur, this protein couldn't be used reliably as a predictive biomarker because not all MCI patients develop Alzheimer's disease.

To conduct their study, the  researchers drew on data available through the Alzheimer's Disease Neuroimaging Initiative (ADNI), a global research effort in which participating patients agree to complete a variety of imaging and clinical assessments.

A computer scientist from the team, used hundreds of amyloid PET scans of MCI patients from the ADNI database to train the team's algorithm to identify which patients would develop dementia, with an accuracy of 84%, before symptom onset.

Research is ongoing to find other biomarkers for dementia that could be incorporated into the algorithm in order to improve the software's prediction capabilities.

While new software has been made available online to scientists and students, physicians won't be able to use this tool in clinical practice before certification by health authorities.

To that end, the team is currently conducting further testing to validate the algorithm in different patient cohorts, particularly those with concurrent conditions such as small strokes.

This is an example how big data and open science brings tangible benefits to patient care."

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Eating walnuts may help ward of several diseases

Eating a diet rich in walnuts may help prevent several diseases prevalent such as cardiovascular disorders, cancer and diabetes, according to an international team of researchers.

The day-long Meeting discussed the role of walnuts in disease prevention and maintenance of healthy lifestyle in the country. Several research findings have shown positive outcomes of walnuts in health issues such as cardiovascular disease, cancer, diseases of ageing and diabetes.

According to a Dr. , metabolic syndrome combined with physical inactivity and under nutrition co-exists, as a double burden on health.

Obesity, hypertension, diabetes and coronary artery disease are like a rising inferno , particularly in urban areas and on the other side of the spectrum we have under nutrition, especially in children, she said.
 
“People should increase consumption of fruits and vegetables, legumes, whole grains and nuts in a daily diet,” said the Dr. “All nuts are rich source of monounsaturated fatty acids (MUFA) and walnuts in addition also contain high amounts of omega-3 fatty acid, making it heart healthy,” she said.

Researchers said that the incidence of dementia has seen an increase of over 10 per cent from its 2010 estimates of 3.7 million to 4.1 million. 

“Walnuts in the diet may improve cognitive function in normal individuals, and reduce the risk or delay the onset or progression of mild cognitive impairment (MCI) and dementia in Alzheimer’s disease (AD),” said a researcher.

The event saw the presence of several international researchers who talked about their area of study on walnuts. “Walnuts are the only tree nut to contain a significant amount of the plant-based omega-3, alpha-linolenic acid, required by the human body,” said a Dr .

“A handful of walnuts also offers four gm of protein, two gm of fibre, and is a good source of magnesium,” said Chopra. “With a variety of nutrients and a flavour profile that pairs well with an array of seasonal foods, they are an ideal ingredient any time of the year,” he said.


These health benefits have been demonstrated through over 180 research papers published since early 1990’s when the commission actively began assessing the role of walnuts in diet and effect on chronic disease prevention.

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