Proposed Alzheimer’s Guidelines Could Lead to Earlier Diagnosis Based on Biomarkers
Determining whether someone has Alzheimer’s disease has traditionally involved a lengthy and complex diagnostic process. Doctors would assess a patient’s medical history, discuss symptoms, and administer cognitive tests. Additional tests such as PET scans, MRIs, or spinal taps would be conducted to detect the presence of amyloid plaques and tau tangles in the brain, both of which are associated with Alzheimer’s. However, new criteria proposed by an Alzheimer’s Association working group may revolutionize the diagnostic process by shifting the focus from symptoms and behavior to biological markers.
The draft guidelines, titled “Revised Criteria for Diagnosis and Staging of Alzheimer’s Disease,” propose a simpler approach that could involve a blood test to detect the presence of amyloid. Some clinics and doctors’ offices already offer such tests. According to Dr. Clifford R. Jack Jr., the chair of the working group and an Alzheimer’s researcher at the Mayo Clinic, “Someone who has biomarker evidence of amyloid in the brain has the disease, whether they’re symptomatic or not.” The scientific consensus is that the pathology of Alzheimer’s exists for years before symptoms appear.
While the working group does not recommend testing individuals without symptoms of cognitive decline, skeptics predict that it will likely happen anyway. This means a significant proportion of people could test positive for amyloid and be diagnosed with Alzheimer’s. A 2015 Dutch study estimated that over 10% of cognitively normal 50-year-olds would test positive, along with almost 16% of 60-year-olds and 23% of 70-year-olds. However, most of these individuals would never develop dementia.
Despite the potential benefits of early diagnosis, many experts and interested parties remain unconvinced about relying solely on biomarkers for diagnosis. The American Geriatrics Society has called the proposed criteria “premature” and highlighted the high proportion of panel members with ties to the pharmaceutical and biotechnology industries, raising concerns about potential conflicts of interest.
The working group embarked on this effort only five years after issuing the previous guidelines due to two significant developments. First, amyloid blood tests proved to be highly accurate, less invasive than spinal taps, and more affordable than brain scans. Additionally, two drugs, aducanumab (brand name: Aduhelm) and lecanemab (Leqembi), received regulatory approval for removing amyloid from the brain, albeit amidst controversy. Studies have shown that these drugs have a modest ability to slow the progression of symptoms in individuals with mild cognitive impairment or mild Alzheimer’s disease.
However, the question remains: Are these developments sufficient to justify diagnosing healthy individuals with an irreversible disease based on a blood test? Dr. Jason Karlawish, a geriatrician and co-director of the Penn Memory Center, considers amyloid “a risk factor, in the way smoking is a risk factor for cancer.” He believes that the evidence is not yet clear and convincing that amyloid alone defines Alzheimer’s disease.
Major studies on amyloid-reducing drugs in cognitively normal people are expected to conclude in 2027 and 2029. If these studies demonstrate that removing amyloid prevents, arrests, or reverses cognitive decline in this age group, it could provide the evidence needed to support the proposed guidelines. However, until then, many experts argue that the guidelines are not ready for clinical practice.
Critics also raise concerns about the potential harms of the new criteria. These include needlessly terrifying people who are unlikely to develop dementia and potentially causing discrimination in employment and insurance. Furthermore, there are concerns about the long-term effects and costs of prescribing amyloid-reducing drugs to asymptomatic individuals. Aducanumab and lecanemab can cause brain bleeds and shrink brain volume, making them potentially dangerous.
Despite the controversy, the working group defends its proposal, emphasizing that the members are committed to accurately reflecting the current scientific understanding. However, critics argue that industry payments and sponsorship can influence guidelines and definitions of diseases. Many patient advocacy groups, including the Alzheimer’s Association, also have ties to the industry.
Redefining diseases and revising guidelines often leads to a broadening of classifications and lowering of thresholds, a phenomenon known as “diagnosis creep.” With amyloid testing as the criterion, there are concerns that there will be a surge in Alzheimer’s disease diagnoses and a push for early detection. However, some patients may welcome an early diagnosis as it could prompt lifestyle changes that may have a protective effect.
In conclusion, the proposed Alzheimer’s guidelines aim to shift the diagnostic process from symptom-based to biomarker-based. While this approach has potential benefits, it also raises concerns about overdiagnosis, unnecessary treatment, and potential conflicts of interest. Further research and evidence are needed before these guidelines can be implemented in clinical practice.
