Doctors' Notes: For Alzheimer’s researchers, the glass is half full
We’re on the verge of a major health crisis, with age-related dementias like Alzheimer’s disease expected to surge — largely due to advances in medicine that are allowing us to live longer.
As a physician and researcher, I see examples every day of caregivers and families struggling to find support as they care for their loved ones. How can we possibly respond to the major repercussions as this crisis grows?
While we haven’t yet found a cure or disease-modifying treatment, we have come a long way in understanding age-related dementia and potential therapies are on the horizon. I choose to see the glass as half full. Armed with this knowledge and possibilities, I believe we can harness the power of basic science and clinical data to find treatments.
One of the biggest advances? We now know what Alzheimer’s in the brain looks like. Through advances in imaging, we can see how Alzheimer’s causes changes in the brain of living humans, and that it’s often accompanied by disease in the brain’s small vessels. We can spot the signature buildup of amyloid and tau proteins in brain scans, and we are working on ways of detecting amyloid plaques in the retina, a more accessible window into the brain. This will make it possible for us to detect Alzheimer’s sooner and potentially provide treatments earlier.
We also know the development of dementias like Alzheimer’s happen over long periods of time — with changes in mental functioning only appearing in late stages. This is why early intervention to stop or slow disease is feasible and strategically a smart way to go.
We are already attempting this in a pioneering research project — called the A4 study — targeting the presymptomatic stage of Alzheimer’s. Cognitively normal people who show an excess of amyloid protein on a PET scan are randomized to receive an anti-amyloid antibody (called solanezumab) or a placebo.
We are also testing another antibody called aducanumab, which targets both toxic soluble amyloid as well as the plaques it generates, in the early symptomatic stage of Alzheimer’s. A paper published last year in the topline journal, Nature, showed positive results, but we need to confirm those findings with larger numbers. At Sunnybrook, we are also exploring focused ultrasound to open up the blood brain barrier in brain regions affected in Alzheimer’s, to give large molecules like antibodies easier access into the brain.
Meanwhile, as we continue to search for medications to slow or stop progression of dementias, we have growing evidence that factors like hypertension, exercise, a heart-healthy diet, adequate sleep, along with social activity, all reduce the risk of developing dementia. What is good for the heart is often good for the brain.
And since we now have ways of “seeing” and measuring dementia in living patients, we are entering a new era of dementia research. By collecting, analyzing and — most importantly — sharing data, we can better tease out the patterns leading to new insights, and act on them.
In Toronto, we’re building up a growing bank of data to share, through the Toronto Dementia Research Alliance. This is an academic coalition made up of five memory and dementia-focused clinics — at Baycrest Health Sciences, the Centre for Addiction and Mental Health, St. Michael’s Hospital, Sunnybrook Health Sciences Centre, and Toronto Western Hospital (University Health Network) — that are all affiliated with the University of Toronto.
Soon, enabled by a Brain Canada grant with institutional matching, if you or your family member arrives at one of our clinics and gives consent, all your intake information and lab results can be stored in a secure database. You’ll also have options to participate in specific research studies and to share your de-identified data, which over a few years will generate important clinical information on several thousand patients.
We are also collaborating with U of T’s Department of Family and Community Medicine to access its extensive patient database for research to help us investigate whether certain types of blood pressure-lowering drugs known as sartans may have more protective brain effects than other antihypertensives. Repurposing drugs already marketed for other conditions is particularly attractive as their safety is already known.
And we are collaborating with other centres, including the Ontario Brain Institute’s Brain-Code and the Canadian Consortium on Neurodegeneration in Aging to share longitudinal patient studies on an even larger scale, using multiple measures such as advanced imaging of the brain and eye and genetic markers.
While we haven’t found a cure for Alzheimer’s and other forms of dementia yet, we now know a lot more and have several scientific avenues to pursue. We are also connecting the dots by bringing together large amounts of data, and making it available to the research community. It won’t produce a silver bullet, but it will help us identify the right combination of lifestyle choices, medications and other potential interventions that will keep this crisis at bay.
Dr. Sandra Black is the executive director of the Toronto Dementia Research Alliance (tdra.ca), the Brill Chair in Neurology and Professor in the University of Toronto’s Department of Medicine, Rehabilitation Sciences Institute and the Institute of Biomaterials and Biomedical Engineering. She is a senior scientist at Sunnybrook Health Sciences Centre, and director of the Hurvitz Brain Sciences Research Program at Sunnybrook Research Institute. Doctors’ Notes is a weekly column by members of the U of T Faculty of Medicine. Email firstname.lastname@example.org .