Why Redefining Alzheimer’s as a “Biological” Condition Is Harmful, and Why the International Working Group Is Pushing Back

In late 2024, the Alzheimer’s Association (AA) introduced new diagnostic criteria suggesting that Alzheimer’s disease can be identified in people who are completely cognitively normal, solely on the basis of abnormal biomarkers such as amyloid or phosphorylated tau. On the surface, this may appear to be a proactive shift toward earlier detection and earlier treatment. But the International Working Group (IWG), a global consortium which includes 46 expert dementia researchers and clinicians from 17 countries, warns that this new direction is not just premature, it is flat out dangerous. According to their analysis, diagnosing Alzheimer’s purely on biological grounds ignores essential clinical realities, misclassifies millions of healthy people, and sets the stage for exposing them to high-risk treatments they do not need.

(Read Medscape report here)

The AA’s criteria treat biomarker abnormalities as if they define Alzheimer’s disease itself. But decades of rigorous research show that many cognitively normal individuals with amyloid positivity will never become symptomatic. For example, a 65-year-old amyloid-positive man has a lifetime risk of Alzheimer’s dementia of only about 22%, a modest increase over background risk. Long-term cohort studies reveal that the vast majority of amyloid-positive, cognitively normal adults do not develop measurable impairment over six to eight years. These biomarker findings represent risk, not disease, and the distinction is crucial. Treating risk as disease turns an enormous segment of the population into “patients” based on a laboratory value rather than on clinical reality.

The IWG maintains that Alzheimer’s must remain a clinical-biological construct. In their framework, Alzheimer’s is diagnosed only when a person has objective cognitive impairment along with supportive biomarker evidence. Biomarker positivity alone is never enough. Individuals who are cognitively normal but show biomarker abnormalities should be described as “asymptomatic at risk,” not as having Alzheimer’s. Only rare situations, such as autosomal dominant mutations or the combination of amyloid PET positivity with widespread neocortical tau, justify labeling someone as presymptomatic Alzheimer’s. This protects people from being incorrectly told they have a progressive neurodegenerative illness when they may remain cognitively intact for life.

Redefining Alzheimer’s biologically opens the door to placing perfectly healthy people on amyloid-lowering monoclonal antibodies such as aducanumab, lecanemab, and donanemab. These drugs offer limited clinical benefit even in symptomatic individuals, yet carry substantial risk. Adverse events include ARIA-E (brain swelling), ARIA-H (brain microbleeds and hemorrhages), and in some cases severe or fatal complications. The risk-to-benefit equation becomes indefensible when applied to someone with normal cognition who may never develop Alzheimer’s symptoms at all.

When the diagnostic definition of Alzheimer’s is based entirely on biomarkers, it becomes easier for physicians, regulators, and industry to justify prescribing these drugs to biomarker-positive individuals even when the likelihood of meaningful benefit is minimal.

Labeling cognitively normal individuals as having Alzheimer’s disease can create deep psychological distress, identity disruption, social stigma, and potential insurance or employment discrimination. With the rapid growth of direct-to-consumer biomarker testing, millions could soon access amyloid or p-tau results without clinical guidance. The IWG warns that a purely biological definition will unleash widespread misdiagnosis, confusion, and unnecessary medicalization. These harms are not theoretical, they are predictable consequences of redefining disease without adequate evidence or context.

The International Working Group’s position is ultimately patient-centered and scientifically grounded. They advocate that cognitively normal individuals with positive biomarkers should be informed that they are at increased risk, not diagnosed with Alzheimer’s disease. These individuals should receive guidance on risk reduction, lifestyle strategies, and careful long-term monitoring, not aggressive pharmaceutical intervention. Biomarker testing in the cognitively normal population should be limited to research settings or structured, non-diagnostic risk assessments. Diagnosis should be reserved for individuals with symptoms, because only then do biomarkers meaningfully anchor prognosis and treatment decisions. This approach protects people from harm, supports informed decision-making, and aligns Alzheimer’s care with principles already used successfully in cardiovascular disease: identify risk, reduce risk, and avoid diagnosing disease where none exists.

The Alzheimer’s Association’s biological redefinition risks creating an epidemic of overdiagnosis, overtreatment, and preventable harm. By turning a risk marker into a disease label, it invites the unnecessary use of amyloid-targeted therapies in people who are completely healthy. The International Working Group provides a safer, more rational framework, one that respects the difference between risk and disease, places clinical findings at the center of diagnosis, and shields individuals from the dangers of inappropriate treatment. Alzheimer’s must remain a clinical-biological diagnosis. To declare normal people “diseased” based on a biomarker is not progress. It is a step backward, one that we can and must avoid.