Research Update: New Ways to Treat Alzheimer’s by Opening the Blood-Brain Barrier

In May 2017, scientists at Sunnybrook Health Sciences Centre in Toronto, Canada made history as the first in the world to use focused ultrasound to temporarily break through the blood-brain barrier (BBB) in patients with Alzheimer’s disease.

The BBB is composed of high-density cells around the smallest blood vessels in the brain, known as the capillaries. While preventing toxic substances in the bloodstream from reaching the brain, this barrier, however, also prevents drug therapies from entering the brain to treat diseases. As Dr. Sandra Black – internationally renowned Brill Chair of Neurology at Sunnybrook Health Sciences Centre and University of Toronto – says, “There are many therapeutic drug treatments that do not work or cannot be properly tested in Alzheimer’s disease because they cannot pass the BBB.”

In November 2015, Sunnybrook researchers successfully opened the BBB for the first time, testing the ability to deliver chemotherapy directly into a patient’s brain tumour. Using MRI-guided focused ultrasound, this recent phase 1 trial in May 2017 was the first time the BBB was opened in patients with Alzheimer’s, although no drug treatments were given. If this trial is successful, researchers will consider conducting another trial to test introducing small amounts of drug therapies through the BBB. They may even target the part of the brain that is most affected by dementia – the hippocampus, which is responsible for creating new memories.

The ability to open up the BBB opens up new possibilities of treating brain disorders. “By opening up the BBB using low frequency ultrasound, we’ve taken a small but important step that opens up a whole new vista of possibilities. The hope is there may be a way to eventually open up multiple little windows, in a gentle way, in order to get large molecules like drugs and even stem cells into the brain,” says Dr. Sandra Black.

More information about Sunnybrook’s research on opening the BBB in dementia patients can be found here: https://sunnybrook.ca/media/item.asp?c=&i=1562&page=33939&f=alzheimers-focused-ultrasound-blood-brain-barrier

Welcome Back from Professor Nathan Herrmann and Student Chair Selina Chow

Last year, a group of students from Havergal College established the Dementia Awareness Program in partnership with Professor Nathan Herrmann - Head of the Division of Geriatric Psychiatry at Sunnybrook Health Sciences Centre. The purpose of our program is to increase the community’s understanding and appreciation of dementia, reduce the stigma associated with mental illnesses, as well as provide the valuable opportunity for high school students to volunteer with, and enrich the lives of people with dementia. While visiting the residents in a dementia care home in Toronto, Canada weekly, we shared our experience and the knowledge we learned about dementia with the community on this blog. Our blog has been a key tool in raising awareness of dementia and de-stigmatizing this common illness. Since we began our blog last year, we received more than 2,000 visits from over 10 countries worldwide - including United States, Russia, Mexico, Germany, Hong Kong, Argentina, France, Australia, Poland, and more.

We are very excited to be gearing up for another year of the Dementia Awareness Program this year, by continuing our community partnership between Havergal College students and a local senior’s residence, while also continuing our blog here. In particular, this year’s blog series will feature current research developments in dementia, along with “Ask the Expert” posts. We want to open up our blog to include your questions about dementia through “Ask the Expert”, which will be answered by Professor Nathan Herrmann. Please feel free to take advantage of this opportunity to ask our world-renowned expert, whether it be about the pathogenesis of the illness or how to interact with a family member with dementia. Questions can be submitted through the comments section on this blog. We look forward to receiving your questions!

We hope this will be of interest to you and the community. Together, we can learn more about this important cause and work to de-stigmatize dementia.

You can also follow Dr. Herrmann’s “Memory Doctor” blog for dementia caregivers at: http://health.sunnybrook.ca/memory-doctor/

Professor Nathan Herrmann and Student Chair Selina Chow

Nathan Herrmann MD FRCPC

Professor, Faculty of Medicine, University of Toronto

Lewar Chair in Geriatric Psychiatry

Head, Division of Geriatric Psychiatry

Sunnybrook Health Sciences Centre

Week 15: Concluding Remarks by Professor Nathan Herrmann and Student Chair Selina Chow

Professor Nathan Herrmann 

The goals of the Havergal Dementia Awareness Project included increasing the community's understanding and appreciation of the problem of dementia, reducing the stigma associated with dementia and allowing a small group of senior students the opportunity to volunteer with, and enrich the lives of people with dementia. 

While many members of the parent body are aware of the problems associated with dementia, and may even have older family members with the illness, there's no question that for many of the students, reading our blog and speaking to our student volunteers, may have been the first opportunity to learn about Alzheimer's disease and other dementias. Given the aging of our society, the number of dementia sufferers is increasing dramatically, and this will lead to a huge burden on many (or most) families, as well as society as a whole. It is therefore essential that all of us are able to appreciate the signs and symptoms of the illness, and be prepared to help people with dementia to ensure their lives are healthy, safe, and as fulfilling and comfortable as possible. We all have a role to play in ensuring these goals.  

By visiting and spending time with a group of seniors with dementia, our Havergal volunteers entertained, comforted and stimulated these individuals, improving their quality of life. They tackled the stigma attached to the diagnosis of dementia by recognizing that people with dementia are no different from you and me – they have good days and bad days; they have likes and dislikes. But we all recognize that everyone with dementia has a similar need to be respected and treated with compassion. The student body can work towards spreading the word about the importance of this illness and the need to improve our understanding about the causes and treatment of dementia. The parent body can help ensure that local, provincial and federal governments are preparing appropriately to help families manage these people so that we don't become overwhelmed. Finally, fundraising for dementia research and the Alzheimer's Society, is something we can all participate in. 

It has been an absolute pleasure for me to work with the school and a fantastic group of dedicated, compassionate students over the past year. I am convinced they have accomplished the goals they set for themselves and wish them congratulations and success in their futures! Finally, I would like to thank the residents and staff at Cedarhurst Dementia Care Home for allowing us into their lives.

Selina Chow (Student Chair), Clarissa Yu, Daniela Krcmar, Katherine Ross, Olivia Nadalini, 
Dr. Erika Friesen

When we first started this Dementia Awareness Project, we were excited to embark on a meaningful journey to learn more about dementia – an illness that we did not know much about. As a group, our first step was to understand the memory loss issues those seniors face, followed by how it affects their daily lives. Before our visits to the dementia care home, we were nervous about how to interact with the residents there. We worried about things that could go wrong, asking questions such as, would they reject our visits? Would they be hostile to us? How should we respond in such circumstances? 

Nevertheless, before our volunteer work began, Dr. Herrmann gave us an overview about dementia and how to interact with someone with dementia. We continued to explore this illness further through readings and writing the weekly blog posts, under the guidance of Dr. Herrmann. As with all new endeavors, we have experienced a steep learning curve. We tried our best to apply what we had learned from Dr. Herrmann and from writing our blog to our weekly interactions with the seniors. During our visits to the dementia care home, some residents were easily approachable, while others were totally unengaged or even expressed frustration. Some would remember us from the previous week, whereas others would have no recollection of our visit. At the end of each weekly visit, we debriefed as a group about the highlights and challenges of our interactions. Every week, Dr. Herrmann has tirelessly explained to us why the residents behaved the way they did, and gave us strategies on how to deal with similar situations. We have learned more than we could have ever imagined from Dr. Herrmann, and our ability to engage with people with dementia has significantly improved. After the first few sessions, we were able to successfully engage the residents in conversation, arts and crafts, and even have a winter holiday sing-along with them! It is amazing to see how much the residents have come to enjoy our visits – a big smile appears on their faces when we arrive, and they always ask when they will see us again at the end of our visit.  

As we finish our volunteer work at the dementia care home for this year, we will miss the residents dearly and look forward to visiting them again soon. We want to thank the staff at Cedarhurst Dementia Care Home, who have supported us weekly and helped us organize all the activities we did with the residents. We also want to thank the residents and their families for allowing us to come into their lives, and trusting us with the stories and memories they hold closest to their hearts.  

While we are far from being experts in dementia, we feel comfortable and confident in dealing with seniors with dementia. We are proud to be ambassadors of this important illness to our school community. We are happy to know that we have raised awareness about dementia among our friends and family, as many of our peers have approached us at school to ask us more about dementia, share with us how they are affected by dementia, and what our work means to them. Of course, this is just the beginning and more can be done to raise awareness of and de-stigmatize dementia. 

We are very grateful to Dr. Herrmann for his unfailing support and encouragement, having mentored and guided us throughout our entire journey this year. Dr. Herrmann has been an excellent role model for us, and we truly appreciate the time he devotes to helping us despite his very busy schedule. We are very honoured to have Dr. Herrmann – an internationally renowned expert – as our mentor. Thank you, Dr. Herrmann.

Finally, we thank our readers for following our 15-week series of our Dementia Awareness Program this year. We sincerely hope that through our blog, you have been able to deepen your understanding of dementia and learn more about what the Havergal College students are doing for this important cause.  

For additional information on dementia, you can also follow Dr. Herrmann’s “Memory Doctor” blog for dementia caregivers at: http://health.sunnybrook.ca/memory-doctor/

Professor Nathan Herrmann and Selina Chow (Student Chair)

Nathan Herrmann MD FRCPC

Professor, Faculty of Medicine, University of Toronto

Lewar Chair in Geriatric Psychiatry

Head, Division of Geriatric Psychiatry

Sunnybrook Health Sciences Centre

Week 14: Future Prospects in Dementia Research

Written by Dr. Nathan Herrmann, MD FRCPC

Lewar Chair in Geriatric Psychiatry
Professor, Faculty of Medicine, University of Toronto
Head, Division of Geriatric Psychiatry, Sunnybrook Health Sciences Centre

As mentioned in a previous posting, at the moment, there are only 4 drugs approved in Canada for the treatment of the symptoms of Alzheimer’s disease. These 4 drugs provide modest benefits at best, and do not change the inevitable progression of the illness. While there has been decades of intense research, Alzheimer’s disease still cannot be prevented, its inevitable progression cannot be appreciably slowed or halted, and even its symptoms cannot be dramatically improved. Research continues however, with scientists generally targeting the 3 major pathological components of the illness which are amyloid, tau, and inflammation.

One of the more disappointing failures in the last several years has been the antibody treatments, including the recent results with solanezumab. This did not slow memory and cognitive decline in a large, lengthy study of people with mild Alzheimer’s disease. This type of treatment, aimed at removing amyloid, has also failed in many other studies with similar agents. There are still a couple of other similar antibody therapies and drugs aimed at reducing amyloid that are going into trials this coming year. These include trials of individuals who do not have Alzheimer’s disease diagnosed, but are at high risk for developing the disease based on family history and/or genetic profile.

Another disappointment this past year was the failure of a drug aimed at tau. Given that the majority of treatments that have been researched to date have focused on amyloid, this much newer focus is potentially exciting, and several antibody treatments for tau are in early development. Finally, a number of drug treatments which effect insulin and blood sugar are being examined given an intriguing relationship between insulin, blood sugar and the development of Alzheimer’s Disease.

Dietary supplements have also received attention recently. Medium chain fatty acids or triglycerides have been studied and are currently being examined in several trials. Coconut oil is an excellent source of these fatty acids, and while likely completely safe, its use cannot be widely recommended at present given the lack of definitive research.

Non-drug therapies are also being studied intensively. Unfortunately, while researchers have been studying treatments like exercise and cognitively stimulating activities like computer games, these interventions have not yet demonstrated that they can effectively prevent or delay the onset of Alzheimer’s disease or other dementias. Direct brain stimulation using electricity, magnetism, and even special lights, is being studied as well.

We are involved in a particularly exciting study aimed at preventing Alzheimer’s disease. This study of over 300 people who are at high risk for developing Alzheimer’s disease will follow people for up to 5 years or longer. We have chosen 2 groups of older individuals who are at high risk of developing dementia – those with mild cognitive impairment (but no dementia), and those who have experienced a clinical depression in the past. These individuals attend an 8 week, daily classroom course of “cognitive remediation” with specialized computer games, as well as receive a safe neurostimulation treatment called transcranial direct current stimulation. While we are about halfway through the study, we are continuing to actively recruit subjects for the trial. If you, or someone you know are interested in this study, please call us at 416-583-1350. Perhaps together we will find a cure for this terrible illness!

Week 13: Student Reflections

            Since November 2016, five high school students, along with their teacher from Havergal College in Toronto, Canada have been visiting residents in a dementia care home on a weekly basis. During our weekly interactions, we engage in conversation and brain-stimulating activities with the residents. Through this experience, we have not only had the incredible opportunity to work with people with dementia, but we have also learned a lot about this illness. We have shared the knowledge we learn about dementia through this blog, and this week, we will be sharing our personal reflections of our experiences.

            Most of us did not have much contact with people with dementia prior to our work at the dementia residence, so this experience was completely new to us. Nonetheless, we were motivated and excited to volunteer with senior adults. Before we began, we were asked “What motivates you to volunteer with senior adults?” Here were our responses:

This is a great opportunity to try something new. I have volunteered with children before by assisting in coaching tennis and swimming programs, and I would also like to be able to help senior adults.

            - Clarissa Yu

It's important to give back, and it helps me appreciate my current life. It's also just important and fair and right to be kind to others in general and to those who may feel especially lonely. Also, I love having the mental capability to go about my life, so I'd like to help give people as much of an opportunity to do that as I can.

            - Daniela Krcmar

I am curious about dementia and love connecting with other age groups.

            - Katherine Ross

I like helping people out, no matter what their age is, in order to make a positive difference in their lives.

            - Olivia Nadalini

I know that senior adults are becoming a larger group in our society, as the population ages. As a result, health-related issues, such as dementia, will become more prevalent. Thus, I am motivated to work with elderlies and do whatever I can to help them. Furthermore, having had memorable experiences with my grandfather who suffers from dementia, I want to help make a difference in the lives of others with dementia.

- Selina Chow

It's satisfying to care for people and contribute to enriching their lives.

            - Dr. Erika Friesen

            Although working with people with dementia was a new experience for most of us, we were fortunate to have amazing mentors – Professor Nathan Herrmann at Sunnybrook Health Sciences Centre, University of Toronto and the staff at the dementia care home. Under their guidance, we have learned how to effectively communicate and interact with a person with dementia. As a result, we were well-prepared in advance to engage with the residents at the dementia home. Going into our first weekly visit, we each had several goals that we hoped to meet from this experience. This is how we responded to the question, “What do you hope to gain from this community partnership?”

I hope to develop a deeper understanding of how to help seniors dealing with dementia and to further understand the condition. I also hope to improve my interpersonal skills.

            - Clarissa Yu

I hope to gain more understanding of these mental conditions that affect a lot of the general population and that will affect many of us in the future. I hope to gain more perspective into senior adults and their perspective on life. Also, it's an important chance to develop my character. It's not often that I get to interact with people of older age and it's a wonderful opportunity to do just that.

            - Daniela Krcmar

Learn about dementia and be able to empathize and relate with others.

            - Katherine Ross

Experience and connect with people.

            - Olivia Nadalini

I hope to learn more about dementia and other related issues that senior adults face, so that I can become an ambassador of dementia to my peers. I believe that knowledge is the first step that we can all take to being able to understand others.

            - Selina Chow

See students develop relationships across differences of age and intellectual ability.

            - Dr. Erika Friesen

            Reflecting back on our memorable weekly visits at the dementia care home, it is safe to say that we not only met our initial goals, but exceeded them. We have made strong intergenerational friendships with the residents and have found so much joy in helping others succeed. As well, we have all learned more about ourselves and improved our interpersonal skills through this experience. Our individual reflections are below.

Clarissa Yu:

My experience with going to the dementia care home has been truly insightful. Before going, I had never had the experience of communicating with someone with dementia. I was unsure of what to expect, and did not know how interacting with the residents would be different from everyday conversations. Nevertheless, I was also excited to be given the opportunity to establish a friendly relationship with a resident. After the first few sessions, I learned that one must learn to be flexible when working with a patient with dementia. At times, the residents that I worked with did not want to do a certain activity, and in that case, it was best to find an alternative one that they would enjoy. Other times, some residents were resting or not interested in having a conversation at all, and then it was best to speak with someone else. However, I found that I greatly enjoyed visiting. Even if I did not consistently speak with the same resident each visit, it was delightful to get to know a few. Each one has a different story and some of their past experiences are incredibly interesting. Many residents also have lots of insightful knowledge to offer and possess a great sense of humor! At times, some of the residents expressed feelings of loneliness, and I was happy that I am able to provide companionship and be there for them to talk to when they felt this way. Overall, visiting the residents has been an extremely positive experience for me, and truly provided me with different perspectives.

Daniela Krcmar:

When I was first given the chance to visit a senior in a dementia home with some other students, I had only some idea of what to expect from previous school visits to a senior home. However, this experience was much more fulfilling than I could have imagined. Being partnered up with a lady with mild dementia gave me a lot of insight into this disease. I became aware of the initial symptoms of this disease that my partner experiences, such as short-term memory problems which led to some repetition in conversations. As well, this experience cleared up many misconceptions I had about dementia, and clearly showed me through conversing with my partner and with the other residents that dementia is experienced differently by each person; some struggle with language, some struggle with short-term memory while having excellent long-term memory, and some struggle in other ways. Finally, and most importantly, I gained a friend through this experience. I always look forward to sharing tea with the lady I was paired up with and talking about anything, and I know she enjoys my company just as much. We’d make jokes about each other and through these weekly interactions, I learned that people with dementia are just like those without it. With, in some cases, a little patience, they can make jokes, and make you laugh, and hear your stories, and tell their own stories, and discuss philosophy just like anyone without dementia can. If someone in your life has dementia, be patient, aware, and understanding of their limitations from their condition, but most importantly, be aware and loving of whom they are underneath. It'll be worth it.

Selina Chow:

            When I first met the resident I was paired up with, I didn’t know what to expect. The only other person with dementia whom I have interacted one-on-one with is my grandpa. However, I knew that people with dementia are unique and have different needs from their peers. I found myself a bit nervous before our first visit – thoughts were racing through my head like: would my partner like me?, what if we have nothing to talk about for the whole hour?, what if a situation arises and I don’t know how to deal with it? Fortunately, it turns out that I was worrying for no reason. My partner and I immediately connected, as she is very warm and friendly and we are both quite talkative. I enjoyed my first visit, and I was looking forward to my next visit the following week so much that seven days felt like an entire year. After my first visit, I realized that my partner is just like me – she is always happy and likes to laugh. Although she does repeat herself and often mixes people’s names and details up, I learned that people with dementia are still full of life. I find that the term “dementia” is often associated with negative connotations that make people feel pity for seniors. I soon realized that there are so many false assumptions about people with dementia in society, such as the belief that they can’t do anything due to their failing memory. As I spent more time with my partner, I was determined to be an ambassador for those with dementia, in order to break down the stigma surrounding memory loss. Just because people with dementia may not be able to communicate as clearly as those without it, that doesn’t mean that we shouldn’t hear their stories. Volunteering at the dementia residence has opened my eyes to the bright side of the illness: people with dementia are just like us, with good days and bad days; they can be independent; they have hobbies; they have emotions. Moreover, there’s so much to learn from them. People often assume that relationships with the elderly are only one-sided, as you have to spend so much energy and time taking care of them without gaining anything in return. In reality, people with dementia have a lot more to teach us than you would imagine. For example, my partner enjoys telling me her stories and sharing life lessons with me. She even treats me as a daughter of her own, and often tells the staff at the residence that even though I’m not her daughter, she wishes I was. Our friendship is a special bond, because I learn as much from her as she does from me.   

  

            Overall, our volunteer experience at the dementia care home has been an eye-opening experience for all of us. We sincerely thank Professor Herrmann and the staff at the dementia care home for mentoring us this year.

Clarissa Yu, Daniela Krcmar, Katherine Ross, Olivia Nadalini, Selina Chow, Dr. Erika Friesen

Week 12: How do we communicate with a person with dementia?

Talking to the person with dementia

1. Never argue, instead agree
2. Never reason, instead divert
3. Never shame, instead distract
4. Never lecture, instead reassure
5. Never say “remember”, instead reminisce
6. Never say “I told you”, instead repeat/regroup
7. Never say “You can’t”, instead do what they can
8. Never command/demand, instead ask/model
9. Never condescend, instead encourage
10. Never force, instead reinforce
http://www.dementiacarefoundation.org/ChallengingBehavior.pdf

Week 11: What are the non-medication treatment approaches? - Part II

Last week we began to review some of the non-medication treatments that have been studied to improve behavior, cognition, function and quality of life for people with dementia. We continue this week with more examples.

• Light therapy
Patients may become more restless and confused in dark environments. It is referred to as ‘sundowning’ and may be caused by an upset body clock. Melatonin is a hormone that keeps our sleeping patterns in tune with the 24-hour cycle of day and night. Every day, as the sun goes down, our levels of melatonin increase and we begin to feel less alert. When the sun comes up, our levels of melatonin decrease quickly. Increasing light levels during the day could help to prevent ‘sundowning’ and disrupted sleep for patients. In light therapy, the patient sits in front of a light box that provides about 30 times more light than the average office light, for a set amount of time each day. This has improved effect on restlessness and on disturbed sleep for patients in some studies.

• Aromatherapy
This may reduce agitated behaviors. Lemon balm and lavender oils have been most commonly used. There is a reduction in behavioral problems in people who received arm massage with lemon balm compared with those who received arm massage with an odorless cream. Lavender oil placed in a sachet on each side of the pillow for at least one hour during sleep may reduce agitated behaviors.

• Nonphysical barriers
They have long been used as a non-restraining method of preventing wandering. They include camouflaging exits by painting them to look like bookcases, painting a black square in front of an elevator to make it look like a hole, and placing a thin Velcro strip across doorways.

• Caregiver support
Help family members care for the patient and themselves.
Caregiver interventions have a positive effect on behavioral problems in patients.
It is important to remind caregivers not to take it personally. Disturbing behaviors of patients lack intentionality and are part of the normal progression of the disorder. Caregivers also need to appreciate that hallucinations are normal in these patients and do not necessarily require medications if they do not disturb the patient or place the patient or anyone else at risk.
Do not try to reason with the patient; instead redirect him or her. Offer caregivers suggestions for reassuring or distracting agitated patients rather than trying to reason with them. Encourage caregivers to maintain routines and consistency. Using low calm tone of voice, giving simple instructions, and leaving and then reattempting care that is refused initially can be effective. Give positive rewards for desired behaviors and do not reward negative behaviors.
Recommend that caregivers create a safe environment. Encourage them to use locks, alarms, or ID bracelets as appropriate if patients are prone to wandering.
Active involvement of caregivers in making choices about treatment distinguishes effective from ineffective support programs, decreases the odds of institutionalization, and may lengthen time to institutionalization.