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January 2025
The Alzheimer’s community is currently in a heated debate about the revised criteria for diagnosing Alzheimer’s disease (AD). In June 2024, the Alzheimer’s Association made waves by suggesting that Alzheimer’s could be diagnosed using biomarkers, rather than symptoms, a shift that surprised many experts. This move is outlined in the “Revised Criteria for Diagnosis and Staging of Alzheimer’s Disease,” which builds on a 2018 framework advocating for a biological definition of the disease.
While the updated criteria are framed as a bridge between research and clinical care, the International Working Group (IWG), comprising 45 scientists, raised concerns. In a recent JAMA Neurology paper, they argued that AD should still be defined by a combination of symptoms and pathology, not just biomarkers. Their suggestion? Label biomarker-positive individuals as “at risk” rather than diagnose them with the disease outright.
Peter J. Whitehouse, MD, PhD, a prominent critic of the new criteria, expressed concerns about the reliability of biomarkers like amyloid PET scans and cerebrospinal fluid biomarkers, which could lead to false diagnoses and unnecessary anxiety. He also highlighted the potential economic burden on the healthcare system, with more people seeking diagnostic tests despite being asymptomatic.
“There’s insufficient evidence to prove that biology is destiny,” Whitehouse said, adding that early diagnosis could be misleading and cause more harm than good.
The Pathology Debate: Does Biomarker Abnormality Equal Alzheimer’s Disease?
The Alzheimer’s Association’s revised criteria suggest that an abnormal “Core 1 biomarker,” such as amyloid PET scans or plasma biomarkers, is enough to confirm an AD diagnosis. Those with abnormal test results but no cognitive impairment are considered at risk. However, the IWG rejected this, arguing that biomarkers alone cannot account for the complex mechanisms underlying Alzheimer’s disease.
Eric Widera, MD, a member of the IWG, criticized the criteria as “bad medicine,” explaining that diagnosing cognitively unimpaired individuals with AD could have serious consequences, such as jeopardizing insurance and employment.
“We don’t even know if amyloid-positive individuals are the right target population for health interventions,” Widera said, pointing out that the emphasis on amyloid might overlook other contributing factors to dementia.
Elyse Couch, PhD, an assistant professor at Brown University, also criticized the push to label asymptomatic individuals with AD. “The evidence doesn’t support this just yet,” she noted, emphasizing that there are still many unknowns in how biomarkers correlate with clinical outcomes.
The Growing Influence of Biomarkers and Pharma
One of the driving forces behind the push for biomarker-based diagnosis is the recent surge in anti-amyloid therapies. These treatments, which include drugs like donanemab and lecanemab, are often marketed alongside the promise that early diagnosis could improve treatment outcomes. However, critics argue that these therapies, still in the early stages of development, could be fueling the drive for earlier diagnoses.
Widera pointed to the role of pharmaceutical companies, such as Eli Lilly, which is actively encouraging consumers to seek biomarker testing via their website. “It’s a marketing strategy to push people into getting tested for amyloid,” he said.
Ronald Peterson, MD, PhD, in a recent editorial, warned of a potential wave of cognitively unimpaired individuals seeking biomarker testing to access treatments that may not be right for them. While some experts, like Maria Carrillo, PhD, of the Alzheimer’s Association, argue that the likelihood of clinicians diagnosing asymptomatic individuals is low, there is concern that patient demand could drive the trend.
Addressing Industry Influence and Conflicts of Interest
The involvement of pharmaceutical companies in the creation of diagnostic criteria has raised ethical questions. Several authors of the revised criteria have ties to drug companies, including Eli Lilly and Biogen, which manufacture anti-amyloid therapies. Whitehouse and others have criticized the potential conflicts of interest, alleging that industry influence may have shaped the recommendations.
Carrillo defended the involvement of industry experts, stating that it is common for guidelines to include such individuals. She emphasized the importance of managing conflicts of interest, though critics argue that the Alzheimer’s Association has not been transparent about how these conflicts were handled.
The National Institute on Aging (NIA), which had previously collaborated with the Alzheimer’s Association on the diagnostic criteria, distanced itself from the final publication due to policy concerns regarding NIH’s use of its name and logo. Despite this, the NIA continues to collaborate with the Alzheimer’s Association.
A Complex Issue
The debate over the revised Alzheimer’s diagnostic criteria is far from settled. While biomarkers may play a role in advancing research and understanding the biological underpinnings of Alzheimer’s, experts agree that caution is necessary when considering their use in clinical practice. The issue of whether biomarker-positive, cognitively unimpaired individuals should be diagnosed with AD is still unresolved, and many experts argue that more evidence is needed before biomarkers can become the primary tool for diagnosis.
The growing influence of pharmaceutical companies and the introduction of new amyloid-targeting drugs have undoubtedly complicated the discussion, adding pressure to adopt these biomarkers in the clinical setting. However, experts like Whitehouse and Widera urge a more cautious approach, emphasizing the need for a holistic understanding of Alzheimer’s that includes both biological and symptomatic factors.
Disclaimer
This article reflects the opinions and concerns of various experts in the field of Alzheimer’s research. The viewpoints expressed are based on current knowledge and available evidence, and the information provided should not be considered as definitive medical advice. As new research emerges, recommendations for the diagnosis and treatment of Alzheimer’s disease may evolve. Always consult with a healthcare provider for individual medical advice and treatment options.
