Current treatment criteria may exclude many people with atypical Alzheimer’s disease even when they remain in relatively early stages.
For some people with Alzheimer’s disease, memory loss is not the first warning sign. Problems with vision, language, planning, or movement can appear earlier, and new research suggests that these less typical symptoms may prevent many patients from qualifying for treatments intended for people in the early stages of the disease.
The study, published August 5, 2026, in Neurology, the medical journal of the American Academy of Neurology, examined eligibility for anti-amyloid therapies among people with atypical Alzheimer’s disease. These treatments are generally used early in the disease, often when memory problems first become apparent.
“Atypical Alzheimer’s disease is often underrecognized and underrepresented in clinical trials,” said study author Dror Shir, MD, of the Mayo Clinic in Jacksonville, Florida, and a member of the American Academy of Neurology. “Our findings suggest that treatment criteria may unintentionally exclude many of these patients, even when they are in the early stages of disease.”
Trial criteria exclude most atypical cases
Researchers examined 184 people whose atypical Alzheimer’s disease had been confirmed through medical testing. Unlike more familiar forms of the disease, their earliest symptoms were not primarily related to memory.
The participants had posterior cortical atrophy, which affects vision and spatial awareness; logopenic variant primary progressive aphasia, which disrupts language and communication; dysexecutive Alzheimer’s disease, which impairs planning and problem solving; or corticobasal syndrome, which affects movement and thinking.
The researchers then assessed whether each person would have qualified for lecanemab or donanemab, two anti-amyloid therapies, using eligibility standards from major clinical trials and treatment recommendations.
Depending on the criteria applied, between 70% and 85% of participants would have been considered ineligible.
Cognitive tests drive most exclusions
Low scores on cognitive screening tests were the leading reason participants failed to qualify, accounting for 50% to 67% of exclusions. Shir noted that people with atypical Alzheimer’s can perform poorly on measures of visual-spatial ability or executive function even while remaining relatively capable in everyday life.
Most participants were still in the early stages of Alzheimer’s disease and could perform many daily activities. Even so, their scores on thinking tests frequently placed them outside the treatment criteria.
The Mini-Mental State Examination, an 11-question screening test, was responsible for most exclusions related to cognitive performance. Brain imaging findings ruled out 22% to 27% of participants, while 19% to 23% were excluded because their dementia was classified as moderate or severe.
“These results suggest a mismatch between how we measure disease severity and how atypical Alzheimer’s disease presents,” Shir said. “Current tools might overestimate the functional stage of the disease.”
The study was retrospective and relied on previously collected clinical information. As a result, the researchers estimated whether patients would have been eligible rather than assessing them directly for treatment.
Reference: “Eligibility for Anti-Amyloid Therapies in Patients With Biomarker-Confirmed Atypical Alzheimer Disease Phenotypes” by Dror Shir, Nick Corriveau-Lecavalier, David T. Jones, Vijay K. Ramanan, Christian Lachner, David S. Knopman, Ronald C. Petersen, Keith Anthony Josephs, Gregory S. Day, Jonathan Graff-Radford and Neill R. Graff-Radford, 5 August 2026, Neurology.
DOI: 10.1212/WNL.0000000000218347
The study was supported by the National Institutes of Health and the Alzheimer’s Association.
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