Research Update: The Challenges of Treating Dementia

With 46.8 million people currently living with dementia and the world’s aging population, there is an urgent need for a treatment to prevent or cure dementia. However, finding a cure for neurodegenerative diseases is very challenging, because these illnesses are hard to diagnose due to the gradual and slow progression of symptoms, as well as the fact that dementia is a complex health problem that can stem from over 50 underlying causes.

Today, most research about potential drug treatments target Alzheimer’s disease, which is the most common form of dementia, accounting for 60 – 70% of all cases. In spite of the high prevalence of Alzheimer’s, we still don’t know enough about the disease’s underlying biology to develop a successful treatment. For instance, it is unknown why the progression of the disease varies between people, or what regulates the toxic build-up of beta-amyloid plaques and tau tangles responsible for Alzheimer’s in the brain. Moreover, patients may have Alzheimer’s disease in addition to other forms of dementia too. Secondly, the blood-brain barrier prevents drugs from reaching the brain through the bloodstream.

Due to these obstacles, some research and clinical trials involving potential dementia drugs have had disappointing results and thus, several companies have stepped away from dementia research. Most recently, pharmaceutical giant Pfizer announced at the beginning of January that it will stop Alzheimer’s research, after costly failed attempts to develop a drug treatment over the past decade.

Nevertheless, there seems to be steps in the right direction for dementia research, as other pharmaceutical companies have continued to test new drugs with modest but promising results. New treatments are targeting the underlying biology of dementia to slow or reverse the disease progression itself. One such approach is called immunotherapy, where antibodies are created to bind to abnormal proteins in the brain – such as the beta-amyloid plaques or tau tangles. These antibodies then expose these abnormal proteins for the body to destroy them.

Non-drug therapies are also being actively investigated – including exercise, focused ultrasound, electrical and magnetic brain stimulation techniques, and cognitive remediation. These techniques, with and without drug therapy, may eventually be shown to be effective at significantly delaying the onset of the disease. Although these may not be “cures”, delaying the onset of Alzheimer’s disease by 5 years can lower the prevalence of the illness by almost 50%.

While it is no easy task to develop a cure for dementia, all dementia research and clinical trials will contribute to our current knowledge of the disease, allowing scientists to create and test new drugs. With perseverance and continued investment in research, we can restore some of what dementia takes away.  

For more information on the challenges and current progress of dementia research, visit https://www.cnn.com/2018/01/18/health/dementia-alzheimers-drug-treatment-partner/index.html

Ask the Expert: Do patients with dementia who live with their family members have better outcomes, compared to those who live alone?

This is a really good question, but allow me to broaden the question a bit.

First of all, does living with a spouse or family prevent dementia? The answer is yes - married adults (and likely those living with family) have a reduced risk of developing dementia. Unfortunately, this protection disappears for widows and widowers who actually have a higher risk of dementia. Although the exact reasons for these relationships are unknown, it is likely that marriage and living with someone enriches their environment and increases social interactions and conversation which are mentally stimulating activities, and known to reduce the risk of dementia. On the other hand, grief and bereavement are stressors that are known to have negative effects on health, especially immune function, and therefore may contribute to an increased risk of developing dementia.

Once someone develops dementia, their ability to perform everyday activities inevitably becomes affected. By the time someone has moderately severe dementia, it is impossible for them to live on their own because they will require help with things like food preparation, shopping, grooming and personal hygiene. So, to answer the question, living with a family will definitely allow them to live longer in their own home, as they require more and more help with activities of daily living. This will significantly increase the time before considering moving to an institution like a nursing home is necessary. Living with family also contributes to a richer environment and more mental stimulation, and this may slow the deterioration of the disease.

Professor Nathan Herrmann

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

Research Update: Post-Traumatic Stress Disorder and Dementia

In the January 2018 issue of the Alzheimer’s Association Journal, an article discussed the relationship between Post-traumatic stress disorder (PTSD) and the risk of dementia. The study was conducted in affiliation with the Kaiser Permanente Division of Research in Oakland, California, the Department of Epidemiology and Biostatistics from the University of California, and the Institute for Health & Aging from the University of California. The study examined many potential direct and indirect links between PTSD and dementia outlined below.

Post-traumatic stress disorder or PTSD is a mental health condition that is caused by experiencing or witnessing an extremely traumatic event such as a car crash. People with the condition often suffer from symptoms such as anxiety, flashbacks, shame, and fear.

In American male and female civilians, it was found that PTSD greatly raised the risk for dementia. Older individuals with PTSD were more prone to dementia, whereas younger individuals with PTSD had a lower risk. It was also found that those with PTSD and depression were at even higher risks for developing dementia. These conclusions were drawn from collecting years of data from individuals across the Northern California region.

In American veterans and prisoners of war with PTSD, the risk for developing dementia is also higher. However, the risk was found to be higher in men than women. Although, there are few studies examining the relationship specifically between veterans with PTSD and dementia, thus more research is needed to further investigate.

There are many potential reasons for PTSD causing a higher risk of dementia. One may be due to the stress that PTSD causes. Studies also found that PTSD can decrease gray matter in areas of the brain that are responsible for memory. There may also be a link between PTSD causing a higher risk for illnesses such as stroke, cardiovascular disease, and diabetes, which in turn translate to a higher dementia risk.

This study is very unique as it is the first to investigate the link between PTSD and dementia, and to provide evidence that PTSD does in fact increase the risk of dementia. For more information, visit http://www.alzheimersanddementia.com/article/S1552-5260(17)30221-2/fulltext#ack0010.

Ask the Expert: Can dementia pass onto the individual's children and grandchildren?

Yes, but it depends! It depends on what you mean by "dementia". As we have explained in previous blogs, most cases of dementia in people over the age of 65 are caused by Alzheimer's disease. There are 2 types of Alzheimer's disease; "sporadic" Alzheimer's disease and "familial" Alzheimer's disease. The vast majority of cases of Alzheimer's disease are the sporadic type, and having a "first degree relative" (e.g. parent or sibling) with the disease, increases your risk of developing the illness by 2-3 times compared to someone your age that doesn't have a relative with the illness. But "familial" Alzheimer's disease is even worse - if you have a parent with the illness, your risk of developing Alzheimer's disease is 50% . The good news here is that familial Alzheimer's disease is exceedingly rare - only 1-2 % of all cases of Alzheimer's disease. Unfortunately, the risks for other types of dementia, like vascular dementia (dementia due to strokes and cerebrovascular disease) and frontotemporal dementia are also elevated for many family members. While we cannot do anything about our genetics, we can all certainly attempt to lead "brain healthy" lifestyles to delay the onset and reduce the risk of developing dementia as we age.

Professor Nathan Herrmann 

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

What It’s Like Having a Grandparent with Alzheimer’s

In all the TV shows I watched as a little girl, the kids would often visit their grandparents on the weekends. Whether it was an episode of Caillou or the Berenstain Bears, the children would always have a fun weekend with their grandparents, as they baked cookies together and looked through old photos. But for me, my weekends with my grandparents were nothing like the TV shows. What I didn’t understand at the time was that my grandfather was beginning to develop dementia.

Since his diagnosis of Alzheimer's disease, my grandpa's condition has only worsened. Sometimes, he leaves the house to go for a walk, but then forgets how to get home and cannot remember his own address. Fortunately, his neighbours help him and bring him home safely. After a few incidents of wandering, we knew that it was too dangerous for my grandpa to leave the house alone. So we installed a second lock on his door. Today, he can’t leave the house alone unless my grandmother unlocks the door.

But the hardest part of this journey is seeing my grandfather become frustrated with his failing memory. "I’m useless; I can’t remember anything" are his most common phrases nowadays. It's really heartbreaking to see him so discouraged.

Despite the burden of this illness on both my grandpa and myself, it is more important that I cherish the moments I spend with him, rather than focusing on his suffering. I'm grateful that he still remembers me and I choose to take each day as it comes, because I never know when it will be the last. I'm afraid of the day when he won’t remember me anymore – when I will no longer be his only granddaughter, but a stranger. The day when he loses his battle to dementia will be the most difficult day. So that's why I hold onto our memories, even if I have to explain to him what a selfie is every time. I’m blessed to hold his hand every step of the way, while this illness takes him away from me. Although his condition deteriorates, I love him unconditionally and hold in my heart the one thing that will never change – dementia will never take away my grandfather and our memories shared together. I will always remember them, as long as I can.

My story is only one in 1.1 million Canadians who are affected directly or indirectly by this disease. For those of you who have a loved one with dementia, know that you are not alone. Yes, it will be difficult, but know that the pain and suffering that comes with the illness is accompanied by the compassion and love we have for them.

Ask the Expert: In the future, will dementia start affecting individuals at younger ages?

No! In fact, in the future dementia will hopefully begin even later in life, if we manage to control obesity, diabetes, high blood pressure, and other vascular risk factors. 

Only a small number of cases of dementia begin in the 50s (and some even in the 40s), and many of these are either cases of "Familial Alzheimer's disease" or Frontotemporal dementias which are strongly genetic illnesses. The most common dementia is Alzheimer's disease which typically begins in the 60s, 70s and 80s. While genetic factors do influence the age of onset of this disease, vascular risk factors also play a role. By reducing the rates of smoking, treating high blood pressure, high cholesterol and diabetes, and reducing the rates of obesity, the onset of this illness could be delayed. Results from the famous Framingham Heart Study in the US have already begun to show the incidence of Alzheimer's disease appears to be declining, likely as a results of the benefits of these interventions. Along with exercise, mentally stimulating activities and a Mediterranean diet, it is possible we can even push the onset of the disease much later into life. Finally, if we can find a disease modifying agent that delays the onset of the illness by even 5 years, we will be able to cut the number of patients with dementia in half. 

Professor Nathan Herrmann

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

Research Update: The Relationships between Dementia and Nutrition

In 2014, researchers from the Global Observatory for Ageing and Dementia Care at King’s College London investigated the relationship between dementia and nutrition. The report, published by Alzheimer’s Disease International, touched on many links between nutrition and dementia, as summarized below.

First, a connection was found between nutrition, fetal development, and dementia, as the micronutrients and fats accumulated as a fetus can affect the development of the brain and nervous system. In turn, this may affect one’s risk of developing dementia in the future. 

In addition, researchers investigated the relationship between dementia and fats. While fats may be harmful for the brain if consumed in excess at mid-life, they can also act as an energy reserve to combat the neurodegenerative effects of dementia. However, further research is needed to explore the relationship between fats and cognitive function.

The report also explained that a Mediterranean diet may be key to preventing dementia. The Mediterranean diet, which consists of lots of vegetables, olive oil and fish, can reduce the risk of cardiovascular disease. As a result, this may potentially reduce the risk of dementia. There are many studies reporting a positive correlation between a Mediterranean diet and a lower risk of dementia; however, some studies have found no correlation at all.

Aside from nutrition and dementia prevention, there is also a link between malnutrition and patients with dementia. Weight loss is very commonly observed in dementia patients due to lower nutritional intake. It was found that dementia-related neurodegeneration may impact brain regions responsible for appetite control, thus contributing to the observed weight loss. The reason why malnutrition is a notable symptom of dementia is because in many cases, it proves to be fatal. This study suggests that eating habits of dementia patients can be improved through: caregiver education about the importance of nutrition, giving patients oral nutritional supplements, using feeding assistance tubes, and more.

For more information on this report, visit http://www.alzheimer.ca/sites/default/files/files/national/breaking-news/adi-nutrition-and-dementia.pdf