Baycrest

BrainMatters • Spring/Summer 2023 • 7 The amyloid hypothesis suggests that if people have amyloid in the brain, they get dementia. But this, too, has been challenged by the fact that many older people with amyloid in their brains don't have dementia. Dr. Howard Chertkow Lecanemab is the second major Alzheimer's drug to receive U.S. federal regulatory approval in the past few years. Before it came aducanumab. Both target amyloid beta, which are sticky protein fragments that accumulate in the brain and are hypothesized as causal factors in the development of dementia. Health Canada did not approve aducanumab for use in this country. Lecanemab is associated with side effects, such as brain swelling, and in some patients, brain bleeding, which can lead to death. As a result, it is uncertain whether this new medication will be widely adopted. My colleague, Dr. Howard Chertkow, the scientific director of the Canadian Consortium on Neurodegeneration and Aging (CCNA), headquartered at Baycrest, and a senior scientist at our Rotman Research Institute, pointed out the challenges with lecanemab in an interview with The Globe and Mail published on February 2, 2023. In the interview, Dr. Chertkow noted that "the amyloid hypothesis suggests that if people have amyloid in the brain, they get dementia. But this, too, has been challenged by the fact that many older people with amyloid in their brains don't have dementia." That said, he also noted that the evidence provided for lecanemab "is clearer than it was for aducanumab" because drug trials showed more clinical benefit. However, the question remains whether the benefits outweigh the costs of this new drug. "Will it mean anything noticeable? That's a big question," Dr. Chertkow told The Globe, and further articulated that patients "may progress from mild to severe dementia in four to five years instead of three to four." Aside from lecanemab, many other types of medications are now being tested for Alzheimer's at major brain research centres like Baycrest, targeting the accumulation of amyloid, as well as other features of the disease, such as brain inflammation. Some evidence suggests the bacteria that causes gum disease, and other types of infections, including viruses such as herpes, may play a role in amyloid accumulation. This implies Alzheimer's dementia may be the result of multiple disease processes, as well as genetic and environmental influences. The future treatment of Alzheimer's might involve a combination of different types of medications targeting the varied potential causes of the condition.

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