Navigating the Path Forward for Dementia in Canada, a Hit and Miss Approach
I read with great consternation the article by Wendy Leung, “Nearly one million Canadians projected to have dementia by 2030, new report says” in the Sept. 6 issue of The Globe And Mail. She quotes Saskia Sivananthan, chief research officer at the Alzheimer Society of Canada as saying that if not much changes to the current trends, the number of people with dementia and the number of people caring for them “is going to be enormous. By investing in addressing modifiable risk factors that improve brain health, we can start changing and shifting some of those numbers down.”
Don’t bet on it. Reading this story, it becomes obvious that the experts employed at the Alzheimer’s Society read and speak only to other like-minded old school scientists largely unaware of the research on neurodegenerative disorders that is being conducted outside their comfortable little bubble.
According to the Alzheimer Society report, Navigating the Path Forward for Dementia in Canada, “Certain risk factors like age and genetics, are not modifiable.” While we all age, how we age is modifiable. We all know people who look and act 10 years younger than their chronological age and vice versa. Being active, having many interests, eating a proper diet, sleeping well, visiting your doctor for yearly check-ups, not neglecting your oral hygiene are just some of the things we can all do to age well.
There is also some really exciting new research about rejuvenation. A study from the University of California San Francisco, showed that exposure of an aged animal to young blood can counteract and reverse pre-existing effects of brain aging by rejuvenating synaptic plasticity and improving cognitive function. This reminds me of the grotesque practice most commonly attributed to the historical figure of Elizabeth Bathory, a Hungarian countess and serial killer who lived from 1560 to 1614. Bathory believed that she could maintain eternal youth and beauty by bathing in the blood of virgins. Macabre yes, but perhaps she was onto something?
Tal Iram, a young neuroscientist at Stanford University, infused instead of blood, cerebrospinal fluid taken from young mice into old mice. For comparison, a separate group of old mice was infused with artificial cerebrospinal fluid. A few weeks later, the mice were exposed to cues — a tone and a flashing light — that they had earlier learned to associate with shocks to their feet. The animals that had received the young cerebrospinal fluid infusion tended to freeze for longer, suggesting that they had preserved stronger memories of the original foot shock.
And as far as genetics go; let me assure you: Genes Are Not Your Destiny. It sounds like people at the Alzheimer Society have never heard of Epigenetics.
Epigenetics is the study of changes in gene activity that do not alter the genes themselves but still get passed down to at least one successive generation. The epigenome sits on top of the genome, just outside it (hence the prefix epi-, which means above). It is these epigenetic ”switches" that tell the genes to switch on or off, to be active and awake or to sleep and keep quiet. It is through epigenetic switches that environmental factors like nutrition, radiation and stress can affect gene expression that is passed from one generation to the next. In other words, how you live will from moment to moment affect the activity of your genes for better or worse.
The report mentions social isolation as a risk factor. True but it does not say anything about the connection between social isolation and the bacteria in our guts, commonly referred to as the gut microbiome, a focus of much research all over the globe. For example, scientists from University of California, La Jolla, CA, found that loneliness was associated with lack of diversity in the gut microbiome. On the other hand, wisdom and compassion was associated with a diverse microbiome. Conversely, the researchers said that social support, compassion and wisdom might confer protection against loneliness-related instability of the gut microbiome. The relationship between loneliness and microbial diversity was particularly strong in older adults.
Healthy, diverse gut microflora may buffer the negative effects of chronic stress or help shape social behaviors that promote either wisdom or loneliness. It is possible that loneliness may result in decreased stability of the gut microbiome and, consequently, reduced resistance and resilience to stress-related disruptions, leading to inflammation and disease.
Surprising new research from Stanford University shows that the buildup of neurofibrillary tangles of tau protein inside neurons in Alzheimer’s, Parkinson’s and other brain diseases which has been assumed was the culprit actually occurs in all aging cells, not just brain cells. Protein aggregation may be a universal phenomenon in aging cells and could be involved in many more diseases of aging than was suspected. Their discovery points to a new way of thinking about what goes wrong in cells as they age and, potentially, to new ways of preventing some unwelcome consequences of aging.
In the Alzheimer’s brain, abnormal levels of beta-amyloid protein, a naturally occurring protein, clump together to form plaques that collect between neurons and disrupt cell function. Pharmaceutical companies and neuroscientists have spent millions of hours and billions of Dollars trying to clear the brain of these amyloid plaques.
Now a new study in the journal PLOS Biology, by John Mamo of Curtin University in Bentley, Australia, found amyloid protein made in the liver when transported to the brain may be a significant contributor to neurodegeneration in the brain. Consequently, it seems logical to assume that the liver may play an important role in the onset or progression of the disease. Has any one at the Alzheimer Society heard of this? Apparently not.
Let’s look at some other plaques, atherosclerotic plaques -- deposits of cholesterol, fibrous tissue and immune cells that form on the inner layer of arteries. These plaques progressively constrict the lumen of the arteries, particularly in the heart and the brain. As a result, less oxygen and nutrients enter these tissues which, unless corrected leads to dementia, strokes heart attacks. What scientists up to now have failed to understand is that atherosclerosis is more than just a plaque, rather it is a chronic inflammatory disease of the entire artery. As a study from the University of Munich recently demonstrated the peripheral nervous system responds to such inflammation and sends signals to the brain. The brain processes the signals and sends a stress signal back to the inflamed blood vessel which in turn reinforces the inflammation, and the atherosclerosis gets worse. This previously unknown communication circuit between the arteries and the brain is potentially of enormous significance and represents a completely new understanding of atherosclerosis. Scientists at the Alzheimer Association – are you listening?
Navigating the Path Forward for Dementia in Canada report advises us to get six to eight hours of quality sleep at night. Good advice. But what if you can’t? A majority of elderly people suffer of insomnia. The reason may be hiding in your gut. Diana Rogulja an assistant professor of neurobiology at Harvard Medical School recently discovered how sleep deprivation causes death in fruit flies and mice. Lethal changes occur not in the brain but in the gut by way of a preponderance of reactive oxygen species (ROS), free radicals. If ROS are not swept up by antioxidant enzymes, they may cause damage to DNA, RNA, and proteins, and may lead to cell death.
Parkinson's disease is a brain disorder characterized by progressive loss of physical movement, including tremors, slow or slurred speech, and/or stiffness or limited range of motion for walking and other physical activities. There is no cure for Parkinson's disease, and it is also associated with behavioral changes, depression, memory loss and fatigue.
Smoking increases the risk of the most common diseases including cancer, cardiovascular disease and pulmonary disease and is definitely harmful to your health. However, and this just goes to show you how complex our bodies are, Parkinson’s is an exception to this rule. Smoking, drinking coffee and high cholesterol decrease the risk for developing Parkinson’s. Reduced risk may reflect an inverse relationship between cardiovascular risk factors and Parkinson disease.
Jens Sundbøll, from the departments of clinical epidemiology and cardiology at the Aarhus University Hospital, Denmark compared the risk of Parkinson's disease and secondary parkinsonism among about 182,000 patients who had a first-time heart attack between 1995 and 2016. When compared to the control group the researchers found there was a 20% lower risk of Parkinson's disease among people who had a heart attack and 28% lower risk of secondary parkinsonism among those who had a heart attack. The risk of Parkinson's appears to be decreased in these patients, in comparison to the general population. Is any one studying the reasons for that?
In conclusion, it appears that there are many avenues open to improve the lives of people suffering of neurodegenerative disorders and, in the long run, to prevent these from occurring in the first place. Unfortunately, many scientists dealing with neurodegenerative diseases are too deeply invested in the current model to initiate change. The message needs to reach the public directly for real transformation. Pressure for reform must come from both inside and outside medicine.
References
Vaccaro, A., Dor, Y. K.., & Rogulja, D. et al., (2020). Sleep loss can cause death through accumulation of reactive oxygen species in the gut. Cell, 181(6), 1307-1328.
Nguyen, T. T., Zhang, X... & Jeste, D. V.et al., (2021). Association of loneliness and wisdom with gut microbial diversity and composition: an exploratory study. Frontiers in psychiatry, 395.
Mohanta, Sarajo K. , Peng, Li , Habenicht, Andreas J. R. et al. ( 2022). Neuroimmune cardiovascular interfaces control atherosclerosis. Nature.
Jens Sundbøll, Szimonetta Komjáthiné Szépligeti, Henrik Toft Sørensen et al. (2022). Risk of Parkinson Disease and Secondary Parkinsonism in Myocardial Infarction Survivors. Journal of the American Heart Association;)
Iram, T., Kern, F., Kaur, A., Myneni, S., Morningstar, A. R., Shin, H., ... &
Wyss-Coray, T. (2022). Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17. Nature, 1-7.
Villeda, S. A., Plambeck, K. E., Middeldorp, J., Castellano, J. M., Mosher, K. I., Luo, J., ... & Wyss-Coray, T. (2014). Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nature medicine, 20(6), 659-663
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