Can robot change Alzheimer's care

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• Nvidia

Will Ludwig the Robot revolutionize Alzheimer's care around the world? Developed by the University of Toronto, see how Ludwig could help patients with Alzheimer's and dementia. 

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As the dementia population around the world grows, healthcare systems are being forced to adapt. Already on the case are Frank Rudzicz, a computer scientist at the University of Toronto and the Toronto Rehabilitation Institute, and his two-foot-tall robotic boy Ludwig, which is powered by machine learning. 

Long passionate about robotics, Rudzicz determined during college that he could have the biggest impact on the field and artificial intelligence if he focused on natural language processing. The field touches many areas of AI, from human interaction and learning to developing knowledge of the world. 

Working on his doctoral project on speech recognition for people with cerebral palsy, Rudzicz learned what machine learning could accomplished in the clinical domain. So, he began looking for opportunities to apply his work in other healthcare scenarios, as well. 

He jumped into the cause, assembling a team at the University of Toronto and Toronto Rehabilitation Institute that started by developing a sort of diagnostic software for dementia, using speech as an input. 

“Language can provide a very deep and accurate lens as to the speaker’s cognitive emotional state, so we started there,” Rudzicz said. “But to be engaging, and to assist people when nurses or caregivers aren’t present, I wanted to develop something a bit more personal.”

What’s Important Is What’s Inside

So Rudzicz and his team decided to build a robot. The result of their efforts is Ludwig, which is being pilot tested at a long-term care facility in Toronto. While Ludwig isn’t the most impressive robot physically speaking, the machine learning algorithms running inside of him, which were trained on NVIDIA TITAN X GPUs, enable him to engage patients in conversation and analyze speech patterns to help assess each patient’s state. 

“We are focusing almost entirely on the software, and have had some success in showing that breakdowns in communication, which are very common in dementia, can be identified by using speech input and neural network models,” Rudzicz said. 

Patients have been signing up to participate in the pilot, and data collection is underway.

Advancing Human-Computer Interaction

Once the pilot is completed, Rudzicz said the next steps will be to further refine the software, and put GPUs to work again building a deep learning-powered neural network that would enable Ludwig to refocus conversations that get off track. Eventually, he has his eye on commercializing Ludwig, but he said that’s probably a few years away. 

In the meantime, he’s zeroed in on establishing the software inside Ludwig as a driving force behind human-computer interaction going forward, particularly in the dementia-treatment realm. 

“We hope that a key outcome of our current pilot will be a measure of how people with dementia feel about interacting with robots, which itself will guide our thinking going forward,” he said. “If the whole community can get interaction right, then products like Google Home and Amazon Echo will become much more entrenched.” 

Ludwick the Robot

Causes of sundowning

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The Ohio State University, 

In "SUNDOWNING SYNDROME," people with dementia show high levels of anxiety, agitation, overactivity and delirium. It typically occurs in late afternoon and evening, before their normal time to go to bed. Learn how brain biology explains “sundowning.” 

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COLUMBUS, Ohio – Valuable research provides the best evidence to date that the late-day anxiety and agitation sometimes seen in older institutionalized adults, especially those with dementia, has a biological basis in the brain.

The findings could help explain “sundowning,” a syndrome in which older adults show high levels of anxiety, agitation, general activity and delirium in late afternoon and evening, before they would normally go to bed.

“It’s a big problem for caregivers.  Patients can get aggressive and very disruptive,” said Tracy Bedrosian, lead author of the study and a doctoral student in neuroscience at Ohio State University.

“There have been a few clinical studies documenting sundowning, but until now there hasn’t been research in animals to see what’s going on in the brain to explain this.”

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The important study found that aged mice showed significantly more activity and more anxiety-like behaviors in the hours before they would normally sleep when compared to middle-aged mice – just like sundowning in humans.

In these aged mice, the researchers found changes in parts of their brain associated with attention, emotions, and arousal, all of which could be associated with the behavior seen in sundowning.

In addition, mice that were genetically engineered to have an Alzheimer’s-like disease also showed more anxiety before sleep than did other mice.

“Some people have argued that sundowning could be explained just by a buildup of frustration of older people who couldn’t communicate their needs over the course of the day, or by other factors,” said Randy Nelson, co-author of the study and professor of neuroscience and psychology at Ohio State.

“But our findings suggest there is a real phenomenon going on here that has a biological basis.”

The study appears in the online Proceedings of the National Academy of Sciences.

In the first experiment, researchers compared middle-aged adult mice (7 months old) with aged mice (29 months old) that would resemble humans in their 80s.

Results showed that the aged mice were significantly more active than middle-aged mice in the two to three hours before they would normally go to sleep.

“The middle-aged mice had a distinct pattern of activity, with three peaks of activity during their waking hours,” Bedrosian said.

“But the aged mice had a flattened rhythm in which they showed the same level of activity throughout their active period.”

Evenings

That means that in the evening, when the middle aged mice would slow down compared to their peak activity levels, the aged mice kept going.

The mice were also tested for anxiety-like behaviors at two different times during their waking hours.  The mice were placed in a maze where they were allowed to explore open areas – which are more anxiety-producing – or hide in enclosed areas.

The middle-aged mice showed consistent levels of anxiety at both times of the day.  However, the aged mice showed more anxiety when tested soon before they would have gone to sleep, which is consistent with sundowning, Bedrosian said.

There were also differences in the brains of the aged mice when compared to the middle aged mice.  The researchers looked specifically at the cholinergic system, because loss of function in that system is associated with dementia and many of the circadian changes associated with ageing.

Findings in aged mice showed greater expression of a certain enzyme – acetylcholinesterase – before sleep than earlier in the day.  High levels of this enzyme are associated with anxiety and agitation.

However, in the middle-aged mice, there were no time-of-day differences in the expression of this enzyme.

Nelson noted that drugs used to control levels of acetylcholinesterase are sometimes used on dementia patients, although there has been no research evidence that it actually had an effect on sundowning.

These drugs include:

Brand Name	Generic Name
Aricept	donepezil
Exelon or Ebixa	rivastigmine
Reminyl or Razadyne	galantamine or galanthamine

“These drugs were prescribed for other purposes, but it also seemed to calm patients down.  Now we have some evidence on why it works,” Nelson said.

Anxiety, Agitation & Proteins

The researchers also found differences in expression of two other proteins in the brains of the aged mice that are also associated with behavioral disturbances.

“All of these results converge to suggest there are changes in the cholinergic systems of aged mice that may be contributing to the anxiety and agitation symptoms that we documented,” Bedrosian said.

In another experiment, the researchers used mice that were genetically engineered to develop Alzheimer’s-like disease in their brain.  They were compared, at nine months of age, to similar wild-type mice of the same age.

The Alzheimer’s-like mice showed more anxiety-type behaviors when tested before they would normally sleep than they did when tested earlier in their waking period.  That is consistent with sundowning in humans, the researchers said.

However, the wild-type mice showed no differences in anxiety levels based on the time of day they were tested.

Nelson said one of the theories about sundowning is that it is tied to disruptions that often occur in the biological clocks of older people, where their sleep-wake cycles are fragmented.

To test this theory, the researchers also treated the aged mice with melatonin for four weeks in order to help consolidate their circadian rhythms.  However, this treatment did not work to reduce anxiety issues in the mice.

Nelson said melatonin alone may not work because it doesn’t deal with the disruptions in the cholinergic system that was identified in this study.

“We need to study whether treating cholinergic dysfunction alone or in combination with melatonin treatment will help deal with sundowning symptoms,” he said.

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SOURCE:
The Ohio State University

Wine for Alzheimer's?

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University of Rochester Medical Center

A new study shows how a daily glass of wine helps clean the brain of Alzheimer's plaque. 

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While a couple of glasses of wine can help clear the mind after a busy day, new research shows that it may actually help clean the mind as well. The new study, which appears in the journal Scientific Reports, shows that low levels of alcohol consumption tamp down inflammation and helps the brain clear away toxins, including those associated with Alzheimer’s disease.

“Prolonged intake of excessive amounts of ethanol is known to have adverse effects on the central nervous system,” said Maiken Nedergaard, M.D., D.M.Sc., co-director of the Center for Translational Neuromedicine at the University of Rochester Medical Center (URMC) and lead author of the study.  “However, in this study we have shown for the first time that low doses of alcohol are potentially beneficial to brain health, namely it improves the brain’s ability to remove waste.”

The finding adds to a growing body of research that point to the health benefits of low doses of alcohol. While excessive consumption of alcohol is a well-documented health hazard, many studies have linked lower levels of drinking with a reduced risk of cardiovascular diseases as well as a number of cancers.

Nedergaard’s research focuses on the glymphatic system, the brain’s unique cleaning process that was first described by Nedergaard and her colleagues in 2012.  They showed how cerebral spinal fluid (CSF) is pumped into brain tissue and flushes away waste, including the proteins beta amyloid and tau that are associated with Alzheimer’s disease and other forms of dementia.  Subsequent research has shown that the glymphatic system is more active while we sleep, can be damaged by stroke and trauma, and improves with exercise.

The new study, which was conducted in mice, looked at the impact of both acute and chronic alcohol exposure.  When they studied the brains of animals exposed to high levels of alcohol over a long period of time, the researchers observed high levels of a molecular marker for inflammation, particularly in cells called astrocytes which are key regulators of the glymphatic system.  They also noted impairment of the animal’s cognitive abilities and motor skills.

Animals that were exposed to low levels of alcohol consumption, analogous to approximately 2 ½ drinks per day, actually showed less inflammation in the brain and their glymphatic system was more efficient in moving CSF through the brain and removing waste, compared to control mice who were not exposed to alcohol.  The low dose animals’ performance in the cognitive and motor tests was identical to the controls.

“The data on the effects of alcohol on the glymphatic system seemingly matches the J-shaped model relating to the dose effects of alcohol on general health and mortality, whereby low doses of alcohol are beneficial, while excessive consumption is detrimental to overall health” said Nedergaard.  “Studies have shown that low-to-moderate alcohol intake is associated with a lesser risk of dementia, while heavy drinking for many years confers an increased risk of cognitive decline.  This study may help explain why this occurs.  Specifically, low doses of alcohol appear to improve overall brain health.”

Additional co-authors include Iben Lundgaard, Wei Wang, Allison Eberhardt, Hanna Vinitsky, Benjamin Reeves, Sisi Peng, Nanhong Lou, and Rashid Hussein with URMC.  Nedergaard maintains research labs at both URMC and the University of Copenhagen in Denmark.  The study was funding with support from the Department of Navy’s Office of Naval Research, the National Institute of Neurological Disorders and Stroke, and the National Institute on Aging.

SOURCE:

• University of Rochester Medical Center

Blood test for a dementia protein

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Nature

Scientists in Japan and Australia have developed a blood test that can identify people who have high levels of a protein associated with Alzheimer's disease. If confirmed by further research, this long-sought test could help in the increasingly desperate search for therapies that halt the progression of dementia, which affects tens of millions of people worldwide.

The test identifies people whose brains have high levels of amyloid-β, a protein that is a key player in Alzheimer’s disease, and which may either cause dementia or be a symptom of it. The researchers hope that drug developers could use the test to recruit individuals with dementia into clinical trials before irreversible damage to their brains has occurred — thus making the trials more reliable.

Molecular biologist Katsuhiko Yanagisawa at the Center for Development of Advanced Medicine for Dementia in Obu, Japan, and his colleagues developed the prototype biomarker test. They published their work online on 31 January in Nature1.

Scientists around the world have been searching for a simple blood test for dementia for the past 15 years. “At first it wasn’t obvious that it would be possible for brain pathology to be measurable in the blood, but we have been getting ever closer,” says neuroscientist Simon Lovestone at the University of Oxford, UK, who has led other studies to find blood biomarkers for Alzheimer’s disease. “This paper provides the best results I’ve seen so far.”

High failure rate

All candidate drugs designed to halt Alzheimer’s disease have failed in clinical trials so far, and many pharmaceutical companies have abandoned the field. Scientists suspect that the design of such trials might be the problem, rather than the drugs being tested. Until now, there has been no reliable way to identify people with the early stages of dementia, so most clinical trials have recruited people whose clinical symptoms are already apparent. At this point, brain damage associated with amyloid-β has already occurred and it may be too late to reverse it, says Yanagisawa.

Until now, the only way to identify amyloid-β in the brain — short of an autopsy — has been to image the brain using positron-emission tomography, or to measure levels of the protein directly in cerebrospinal fluid from the spinal cord. Both of these procedures have been used to help recruit patients into recent trials, but the tests are expensive and uncomfortable.

To measure the levels of several amyloid-β fragments in blood samples, as well as a fragment of a larger protein from which amyloid-β derives, Yanagisawa and his colleagues combined two existing techniques — immunoprecipitation and mass spectroscopy. Their results matched those achieved through brain imaging and the analysis of spinal-cord fluid in two separate cohorts involving 121 people in Japan and 252 people in Australia. Each cohort included individuals aged between 60 and 90. Some of the participants were healthy; some showed mild impairment in their cognitive skills; and some had Alzheimer’s disease.

The authors say that larger and more long-term studies are needed to confirm how accurate the blood test is at identifying high levels of amyloid-β in human brains. If it is highly accurate, then the test could help recruitment for clinical trials, because it is relatively easy and cheap to do.

Does Vitamin E slow down Alzheimer's?

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Mount Sinai Medical Center, via Newswise.

Vitamin E may slow down Alzheimer's and ease caregiving, according to a JAMA report. See how vitamin E improved daily activities in dementia, including shopping, preparing meals, planning and traveling. 

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Difficulty with activities of daily living often affect Alzheimer's patients. Disruption to daily routine is one of the hardest burdens for caregivers. New research suggests that Vitamin E may slow functional decline in patients with mild-to-moderate Alzheimer's disease. This includes problems with daily activities such as:

• Shopping
• Preparing meals
• Planning
• Traveling

It appears to also decrease caregiver burden. There was no added benefit for memory and cognitive testing with the vitamin.

Continued below video...

The research was performed by the faculty of Icahn School of Medicine at Mount Sinaiworking with Veterans Administration Medical Centers. The study is published online in the Journal of the American Medical Association.

The researchers investigated vitamin E as α-Tocopherol, an important fat-soluble antioxidant. Mary Sano, PhD, was the trial co-investigator, and professor in the department of psychiatry, Icahn School of Medicine at Mount Sinai, and director of research at the James J. Peters Veteran's Administration Medical Center, Bronx, New York. She said,

"Since the cholinesterase inhibitors [Aricept/donepezil, galantamine, rivastigmine], we have had very little to offer patients with mild-to-moderate dementia."

"This trial showed that vitamin E delays progression of functional decline by 19% per year, which translates into 6.2 months benefit over placebo."

The finding is valuable because vitamin E is easy to purchase at local drugstores and it is also inexpensive. The clinical trial investigators believe it can be recommended as a treatment strategy, based on the double-blind randomized controlled trial.

The Veteran's Administration Cooperative Randomized Trial of Vitamin E and memantine in Alzheimer's Disease (TEAM-AD examined the effects of vitamin E 2,000 IU/d, 20 mg/d of memantine, the combination, or placebo on Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Inventory Score. Cognitive, neuropsychiatric, functional, and caregiver measures were secondary outcomes. A group of 613 patients with mild to moderate Alzheimer's disease were in the study, which was launched in August 2007 and finished in September 2012 at 14 Veterans Affairs Medical Centers. 

Dr. Sano previously led a study on Vitamin E in patients with moderately severe Alzheimer's disease. She found that the vitamin slowed disease progression in this group of patients as well.

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Expert explores diet and Alzheimer's risk

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Cure Alzheimer's Fund

Harvard's Dr. Rudolph Tanzi, one of the world's best-known Alzheimer's researchers, explores lowering the risk. Topics include turmeric, vegetarianism, coconut oil and what he actually applies to his own daily life. 

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Summary of Video: (Watch the video for more details on these topics.)

Do vegetarians get Alzheimer's at lower rates than meat-eaters?
We don't know that. Most vegetarians still eat dairy products, so they're still getting animal fat in their diets. It'll be interesting to see whether vegans, who eat no animal products, get Alzheimer's. That study hasn't been done yet. 

The only data about vegetarianism is with animals - old carnivores get Alzheimer's; old herbivores don't (so far).

Thoughts on turmeric?
Turmeric lowers amyloid production and aggregation…in a petri dish. The problem with turmeric (or more specifically, the 'active ingredient' curcumin), is that it doesn't get into the brain very well, and therefore can't help much with Alzheimer's pathology. There are other good things about curcumin, though - some studies say it could have anti-cancer effects.

At Cure Alzheimer's Fund, we're developing some curcumin-like compound that can get into the brain. If these can be made safe, they may be effective against Alzheimer's.

What about coconut oil?
I'd like to see a real trial. I'm intrigued by the anecdotes, but as a scientist, you get burned by anecdotes all the time. There are companies doing some trials now. Non-virgin coconut oil can have negative health effects - it raises your triglycerides.

What do you, Dr. Tanzi, do to lower your own risk of getting Alzheimer's?
I stay intellectually and socially engaged. I'm a vegetarian - we don't know for sure, but I do think that will help. The only supplement I take is called ashwagandha, which has anti-amyloid effects. Unfortunately, most of the ashwagandha you'll find online does not work. The best one comes from Douglas Labs, but you need to get it through a doctor.

Decrease antipsychotic use in dementia by 20 percent

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SOURCE:

• University of Massachusetts - UMASS Medical School

DRUGS: 100 care facilities saw a significant drop in antipsychotics for dementia when staff were trained to focus on "treating the residents as human beings with needs, not as patients with problems." Find out more about this study, the largest of its kind, ever. 

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The use of antipsychotic medication in nearly 100 Massachusetts nursing homes was significantly reduced when staff was trained to recognize challenging behaviors of cognitively impaired residents as communication of their unmet needs, according to a new study led by Jennifer Tjia, MD, MSCE, associate professor of quantitative health sciences. Results of the study were published in JAMA Internal Medicine on April 17.

Reduce Use

“This is the largest study to show that it is possible to reduce antipsychotic use in the nursing home population,” said Dr. Tjia. “This intervention focused on treating the residents as human beings with needs, not as patients with problems. We don’t medicate babies when they cry or act out, because we assume that they have a need that we need to address. However, when people with dementia are unable to communicate, the current approach medicates them when they have 
The off-label prescription of antipsychotics for nursing home residents with dementia is common, despite numerous studies that have shown it increases risk of stroke and death and is only minimally effective in controlling behavioral symptoms of dementia.

Meet the Needs of Residents

Tjia studied the influence of a communication training program called “Oasis” for nursing home staff on off-label antipsychotic use. The Oasis curriculum and training—launched by the Massachusetts Senior Care Association in collaboration with the Massachusetts Department of Health and developed by geriatric psychiatrist Susan Wehry, MD,—equips frontline nursing home staff, such as nursing assistants, nurses, dietary staff and receptionists, with the knowledge, skills and attitudes to meet the needs of residents with dementia using nonpharmacologic approaches rather than medication. Ironically, the program reached very few prescribers, but was still able to significantly reduce antipsychotic use. 

“The Oasis program asks nursing staff to create care plans that include what residents can do, shifting away from the model that focuses on what they can’t do,” Tjia said. “This is a fundamental shift in how to think about caring for persons with dementia and we showed that it is effective.”

Significant Drop

This study examined the rate of off-label antipsychotic use in 93 Massachusetts nursing homes enrolled in the Oasis intervention from 2011 to 2013, compared to 831 nursing homes in Massachusetts and New York who were not using that program, (although some were using a different reduction program.) Among Oasis facilities, the prevalence of antipsychotic prescriptions was cut from 34 to 27 percent after nine months, a 7 point drop, making for a relative 20% decrease. At the comparative facilities, the prevalence of those drugs was cut from 23 to 19 percent; a 4 point drop. No increases in other psychotropic medicine or behavioral disturbances were observed. Over the maintenance period of the intervention, however, the decreases did not continue. 

“Since 1987, no fewer than 11 controlled studies have been published that report varying efficacy in reducing antipsychotics in nursing homes using a variety of approaches. The largest successful intervention enrolled 12 nursing homes; however it was time and resource intensive. In contrast, the Oasis program reached almost 100 nursing homes, and was effective,” Tjia said. 

Tjia said nursing homes using the Oasis program need to reinforce training periodically to maintain success at reducing the rate of antipsychotics. 

REFERENCE:

• April 17, 2017, Association of a Communication Training Program With Use of Antipsychotics in Nursing Homes ,
  Jennifer Tjia, MD, MSCE1; Jacob N. Hunnicutt, MPH1; Laurie

undesirable behaviors.” 

Boost memory with saffron chicken

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n a double-blind study, saffron spice beat out placebo in the treating symptoms of Alzheimer's. Try this healthy saffron chicken dish. 

Ingredients:

• 4 chicken breasts
• 1 medium onion
• 3 teaspoons liquid saffron
• Salt and pepper

Method:

1. Slice the onion finely.
2. In a pan, add the onion, salt, pepper and three or four tablespoons of water.
3. Lay the chicken breasts on top.
4. Cover and simmer for 30 minutes on low heat until the chicken becomes soft and tender.
5. Add the liquid saffron over the chicken breasts
6. Turn them over a couple of times to coat thoroughly in the saffron sauce.

Serve in a shallow dish with veggies of choice.

Enjoy the Recipe!

Consume foods with vitamin D to greatly decrease dementia risk

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American Academy of Neurology,

In the largest study of its kind, not getting enough vitamin D turned out to double the risk of developing dementia and Alzheimer’s. See why supplements may not be the answer. Find out which foods to eat.

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MINNEAPOLIS – In the largest study of its kind, researchers suggest that in older people, not getting enough vitamin D may double the risk of developing dementia and Alzheimer’s disease. The study is published in the online issue of Neurology®, the medical journal of the American Academy of Neurology. 

Continued below video...

The study looked at blood levels of vitamin D, which includes vitamin D from food, supplements and sun exposure. Dietary vitamin D is found in:

• Fatty fish such as salmon, tuna or mackerel
• Milk
• Eggs
• Cheese

"We expected to find an association between low Vitamin D levels and the risk of dementia and Alzheimer's disease, but the results were surprising—we actually found that the association was twice as strong as we anticipated," said study author David J. Llewellyn, PhD, of the University of Exeter Medical School in the United Kingdom. 

For the study, 1,658 people over the age of 65 who were dementia-free had their vitamin D blood levels tested. After an average of six years, 171 participants developed dementia and 102 had Alzheimer's disease. 

The study found that people with low levels of vitamin D had a 53 percent increased risk of developing dementia and those who were severely deficient had a 125 percent increased risk compared to participants with normal levels of vitamin D. 

People with lower levels of vitamin D were nearly 70 percent more likely to develop Alzheimer's disease and those who had severe deficiency were over 120 percent more likely to develop the disease. 

The results remained the same after researchers adjusted for other factors that could affect risk of
 "Clinical trials are now needed to establish whether eating foods such as oily fish or taking vitamin D supplements can delay or even prevent the onset of Alzheimer's disease and dementia. We need to be cautious at this early stage and our latest results do not demonstrate that low vitamin D levels cause dementia. That said, our findings are very encouraging, and even if a small number of people could benefit, this would have enormous public health implications given the devastating and costly nature of dementia," said Llewellyn. 



dementia, such as education, smoking and alcohol consumption.