January is Alzheimer鈥檚 Awareness month and two new studies at the Clinical Research Unit at The Neuro are tackling cognitive decline with the goal of helping older Canadians remain independent longer. One study looks at how a computerized brain-training program may improve focus and the brain鈥檚 ability to stay in shape; the other is investigating a potential new therapeutic avenue in slowing the progression of early Alzheimer鈥檚 Disease.
Gaming the brain
According to the Alzheimer鈥檚 Society of Canada, almost 40% of people over the age of 65 experience some form of memory loss, known as age-associated memory impairment. The accepted wisdom is that, in order to stave off further cognitive decline and possible dementia, we need to keep our brains active. But how do we know what really works to keep us sharp?
鈥淚n my clinic, I see patients with memory problems, and they're worried. They tell me that they are doing crossword puzzles every day; but we now know that crossword puzzles don't do much,鈥� explains Dr. Etienne de Villers-Sidani, a neurologist specializing in cognitive disorders at The Neuro (Montreal Neurological Institute-Hospital). 鈥淚n order to show benefit, we need a type of training that involves your senses, that involves your attention and that gets harder and harder over time.鈥�
Dr. de Villers-Sidani is the principal investigator for the INHANCE study taking place at the Neuro鈥檚 . This study is looking at the impact of a computerized brain training program designed by Posit Science at UCSF that hopes to show improved neurological health by targeting speed and alertness training. The study will not only look at participants鈥� scores on standard measures of cognition, but will also evaluate their levels of acetylcholine, a chemical produced in the brain when we focus, through novel brain imaging techniques.
鈥淎s we get older, the chemicals in the brain that are important for attention and for brain plasticity --meaning the ability of the brain to change -- tend to go down naturally. And that process becomes accelerated in a number of neurodegenerative disorders, like Alzheimer's disease,鈥� says Dr. de Villers-Sidani.
Powered by positrons
In 2017, the Alzheimer鈥檚 Association published the results of a 10-year study in the US that found that individualized computerized brain training reduced the incidence of developing Alzheimer鈥檚 by almost 30%. The INHANCE study aims to go one step further by examining whether this type of brain training can actually change the chemistry of the brain in a fundamental way.
鈥淭here is no data out there on this. What we're trying to do with this study by tracking acetylcholine is to demonstrate that the brain can upregulate, and increase its production of this very important chemical for healthy brain function,鈥� explains Dr. de Villers-Sidani.
Posit Science received funding from the National Institutes of Health in the US for the INHANCE study and contracted the Clinical Research Unit at The Neuro to conduct the trial. The Neuro is well known for its positron emission tomography (PET) unit, an emerging technology for the clinical evaluation of many disease processes.
鈥淭he Neuro is one of the only places in the world that is equipped to measure levels of acetylcholine in the brain. The ligand -- a molecule that binds to a receiving protein 鈥� that is used in the imaging was developed for the first time in collaboration with the PET unit at The Neuro. It鈥檚 only been used in a handful of other places in the world,鈥� adds Dr. de Villers-Sidani.
The INHANCE trial is looking for healthy participants over the age of 65 who would use this daily brain training program 30 minutes a day at home for several weeks. Anonymous data from the study will also be available following the end of the study in LORIS, an open science data-imaging platform at The Neuro that will allow researchers from around the world to request access to further their research.
Dr. de Villers-Sidani is hopeful that this speed and alertness training could make a real difference. 鈥淚f the results of the study are positive, that could have an impact on clinical management relatively soon, because this software already exists.鈥�
Treating Alzheimer鈥檚 early
The Alzheimer鈥檚 Society of Canada estimates that there are half a million people over the age of 65 living with dementia today, and that number is set to almost double in the next decade. Dementia is an umbrella term for a set of disorders, including Alzheimer鈥檚 Disease, that impair brain function. The symptoms include a decline in memory, language and judgement; physical challenges with balance and movement; as well as changes in mood and behaviour. These are chronic conditions that gets more severe over time.
The is the only site in Quebec taking part in a major international trial testing a new medication that hopes to slow cognitive decline in participants who already have early Alzheimer鈥檚 Disease. This Phase II trial will test a potential new medication鈥檚 safety and as well its effects on the accumulation of tau protein in the brain.
鈥淭here are two major abnormalities leading to symptoms in Alzheimer's disease. There are amyloid-beta plaques and there are neurofibrillary tangles caused by an accumulation of a protein called tau that collects inside neurons,鈥� explains Dr. Simon Ducharme, a neuropsychiatrist and the director of the Geriatric Psychiatry Division at 平特五不中, who is the principal investigator on the AuTonomy clinical trial at The Neuro.
Tangling with tau
鈥淭he interesting thing about tau is that it accumulates in the places in the brain related to symptoms -- for instance the memory centers around the hippocampus -- while beta-amyloid plaques are more dispersed. There is therefore an important link between these accumulations and the actual symptoms of dementia. Yet the approach of targeting tau has been much less explored in trials testing new treatments,鈥� says Dr. Ducharme.
To date, the great majority of studies testing new medications to treat Alzheimer鈥檚 have focussed on amyloid-beta and they largely have not been successful at slowing disease. A recently approved medication showed mild slowing of disease progression, but patients continued to deteriorate on the treatment. 鈥淭he hope is that by targeting tau, this study will lead to a disease modifying therapy, one that can stabilize or significantly slow down the progression of the disease,鈥� says Dr. Ducharme.
The AuTonomy study is for those with early stage Alzheimer's disease or mild cognitive impairment (MCI) with evidence of elevated brain tau. This is a stage where patients have biological changes in their brain and may experience memory loss, word finding issues and difficulty with orientation. 鈥淎t this stage we can see from the biological tests that these issues are caused by Alzheimer's disease in the brain, but these individuals remain fairly independent,鈥� explains Dr. Ducharme.
The experimental medication tested in the AuTonomy study is innovative; it is testing a passive antibody mechanism that binds to specific forms of phosphorylated Tau to facilitate its elimination by the brain鈥檚 microglia. In other words, it has the potential to decrease the spreading of tau in the brain, which could slow down disease progression.
鈥淭here is probably going to be a point where we can combine these different approaches 鈥� amyloid-beta and anti-Tau. Our current research is really building the arsenal to slow down the progression of the disease. The ultimate goal would be to see a stabilization of Alzheimer鈥檚 Disease,鈥� concludes Dr. Ducharme.
For more information on these two studies, contact the neurocognitive team at the Clinical Research Unit at The Neuro at info-cru.neuro [at] mcgill.ca or visit
