How the treatment landscape for Alzheimer’s may be set to change

In Alzheimer’s Dementia (AD) treatment, there is a new push to diagnose it as a biological disease. The new criteria comes from the U.S. Alzheimer’s Association, which published the “Revised Criteria for Diagnosis and Staging of Alzheimer’s Disease” in its journal last year. The 2024 update includes an updated biomarker classification system, said Dr. Mireille Norris, a geriatiician at Toronto’s Sunnybrook Health Sciences Centre. “We’ve seen a correlation between the presence of abnormal proteins in cerebrospinal fluid (CSF) and Alzheimer's,” said Dr. Norris. “[Testing] is not something that is available right now, but this is where the field is moving.” Dr. Norris presented these and other new advancements in pharmacotherapy for treating dementia at the Black Physicians Association of Ontario’s (BPAO) 16th annual Health Symposium in February. The new criteria, from the National Institute on Aging and the Alzheimer’s Association, indicates that “changes in early-changing Core 1 biomarkers like amyloid positron emission tomography (PET), approved cerebrospinal fluid markers, and accurate plasma biomarkers (especially phosphorylated tau 217) map onto either the amyloid beta or AD tauopathy pathway, however, these reflect the presence of AD neuropathologic change more generally, i.e. both neuritic plaques and tangles.”“What it shows is that mild cognitive impairment (MCI) and a positive Core 1 biomarker indicates MCI due to AD,” said Dr. Norris. The diagnostic radiotracer to visualize B-amyloid plaques (PET amyloid) has already been approved in Canada, but clinical research is still being done on plasma, she said. As we wait for research and clinical trials, diagnosing early AD and mild dementia is important, said Dr. Norris. “There are potentially reversible causes of mild dementia, and viable, unaffected brain to protect.” She recommended physicians do blood work to check for reversible facets of dementia like testing for a complete blood count, lytes, creatinine, liver function test, glucose, lipid profile, B12 and calcium. Beyond blood work, she recommended an MRI for hippocampal atrophy and white matter changes, that patients with hearing impairment use hearing aids, checking for sleep apnea and other causes of sleep disruption.Brain-healthy lifestyle strategies like sleep, hearing, exercise, nutrition, healthy hearing and vision and healthy socialization can all help delay the disease’s development, she said. Pharmacotherapy treatmentsFor symptomatic treatments, cholinesterase inhibitors like donepezil, galantamine, and rivastigmine have been approved for mild-to-severe dementia, while glutamate modulators like memantine have been approved for moderate-to-severe dementia.“Pills are available, but their impact is mild to modest,” said Dr. Norris. Disease-modifying therapy: the new frontier? New disease-modifying therapies (DMT) are also being tested for the treatment of AD.A DMT intervention will try to change the clinical progression of the disease by interfering in the underlying pathophysiological mechanisms of the disease process that leads to cell death. Lecanemab and donanemab, two anti-amyloid antibodies, have been approved by the U.S. Food and Drug Administration for early AD. The treatments have been shown to clear amyloid from the brain and can render PET amyloid scans negative. They slow cognitive and function decline and delay the progress to the next stage of the disease. In Canada, lecanemab, which is delivered intravenously by infusion every two weeks, is pending Health Canada approval, and referral to the specialized Memory Program is needed for patients to access expertise like geriatricians and neurologists, PET imaging, CSF markers, and the infusion program. “The therapy is controversial because our healthcare system is already in crisis and the treatments are $20,000 or more per person,” said Dr. Norris. “But it does show that there is new hope for dementia.”

How the treatment landscape for Alzheimer’s may be set to change

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