The emergence of monoclonal antibodies for the treatment of Alzheimer’s disease, like lecanemab and donanemab, has been touted as a significant milestone in dementia care. For several years, the therapies were unavailable in Canada. This situation changed recently with Health Canada’s approval of lecanemab, which is leading to a shift in the way geriatricians and neurologists approach the diagnosis of dementia.

“For the first time, there’s not this idea of therapeutic nihilism in dementia care,” David Tang-Wai, MD, division director in the Department of Neurology at the University of Toronto, Toronto, and the co-director of the University Health Network memory clinic, told Medscape News Canada. “There is something now that we can clearly offer other than a cholinesterase inhibitor that has the significant potential to slow this disease down.” 

The goal of earlier diagnosis of Alzheimer’s disease is associated with the goal of initiating earlier treatment. It requires responses to some of the most common concerns, which include the lack of disease-modifying drugs, increased worries on the part of patients and families, limited prognostic value of biomarkers, and financial or resource burdens. The International Working Group has examined these concerns.

With Health Canada’s approval of lecanemab and its ongoing review of donanemab, it is now possible to address these concerns. The emergence of a disease-modifying drug addresses patients’ and families’ fears about a diagnosis that they couldn’t treat.

Among patients diagnosed early with minimal functional impairments, those who are treated are more likely to remain high-functioning, Jaspreet Bhangu, MB, Bch, clinician researcher and geriatrician at Western University in London, Ontario, told Medscape News Canada.

The lecanemab and donanemab studies demonstrated over 30% reduction in progression to the next stage of dementia over 18 months. Though these results do not represent a cure, they provide patients a greater period of independence that allows them to fulfill their last wishes and obtain closure.

Presently, anti-amyloid therapies are approved for treating mild cognitive impairment and mild stage dementia with Alzheimer’s pathology. To initiate treatment, a definitive diagnosis using biomarkers such as amyloid PET or cerebrospinal fluid is required, instead of the traditional approach based on the patient’s day-to-day function. This requirement highlights a need to identify patients earlier in their dementia trajectory, where intervention is possible and has the best outcome.

The concerns about limited prognostic value of biomarkers stem from studies previously demonstrating that the presence of amyloid plaques in the brain does not equate to clinical disease. In older adults, multiple concurrent pathologies are often the cause of dementias. While the exclusion criteria of the monoclonal antibodies attempt to target only patients with true Alzheimer’s pathology, the worry is that in patients where amyloid is present but not the primary driver of dementia, anti-amyloid treatments can entail more serious and long-lasting risks compared with existing treatments.

The adverse outcome of greatest concern is amyloid-related imaging abnormalities (ARIA), which can present as either edema or microbleeds on imaging. Nearly 1 in 5 patients had complications of ARIA in the initial studies of lecanemab.

When appropriate patients are selected carefully, the rate of ARIA is much lower, and few patients are symptomatic, said Tang-Wai and Bhangu. Furthermore, a key difference in the approval of lecanemab in Canada is the exclusion of patients who have two copies of the APOE4 gene variant, which is associated with higher risk for ARIA.

The cumulative savings from treatment may minimize healthcare utilization and delay institutionalization, thus making the cost worthwhile, said Tang-Wai. While the pricing of lecanemab in Canada is not yet clear, the method for calculating cost-effectiveness is understood.

Now that the major concerns about the earlier diagnosis of dementia are being addressed, changing practice at the subspecialist level may not be enough. It is the hope that front-line practitioners will become involved through earlier referral of patients with cognitive concerns for assessments.

Family practitioners across Canada generally have been uncomfortable commenting about how they might change their practice. They cite the lack of guidance from federal and provincial levels, as well as a lack of certainty about access to lecanemab.

Geriatric psychiatrists and geriatricians could be involved in the rollout of the monoclonal antibodies for broader access, just like they are involved in available treatments, Aditya Nidumolu, MD, geriatric psychiatrist at MacKenzie Health in Vaughan, Ontario, told Medscape News Canada.

It should be a “collaborative approach with geriatric medicine, neurology, and geriatric psychiatry in…some type of centralized or regional center that’s taking the lead, that has these pathways and the ability to access [anti-amyloid therapy],” he emphasized.

Although the process for establishing these access pathways is not completely clear, one thing is certain: The approach to the diagnosis of dementia is changing and will continue to change.

“I would always recommend that people get on board early so that they can figure out how to integrate biomarker or biological diagnosis,” said Bhangu. “This is just the beginning.”

Tang-Wai reported receiving honoraria from Eisai for providing input on their medication. Bhangu is a paid consultant for Eli Lilly and Eisai and is a site principal investigator for a clinical trial sponsored by Eisai. Nidumolu reported no relevant financial relationships.

Allen Chang, MDCM, is a geriatric medicine subspecialist at Nova Scotia Health Authority and an assistant professor at Dalhousie University in Halifax. He has interests in medical media and the integration of technology into everyday patient care.