Most people with less common forms of Alzheimer's disease would not qualify for the anti-amyloid drugs designed to slow it, according to research published August 5 in Neurology.
Among 184 people with biomarker-confirmed atypical Alzheimer's disease, between 70 and 85 percent would not meet the eligibility criteria for lecanemab or donanemab, the study found. Many of them were still in the early stages of their disease and could manage many daily activities.
The reason is the part families should understand. The single largest driver of exclusion was performance on cognitive screening tests, which accounted for 50 to 67 percent of exclusions, most often scores on the Mini-Mental State Examination. That is an 11-question screen weighted toward memory. A patient whose Alzheimer's attacks vision or language first can score poorly on it while still functioning relatively well.
Atypical Alzheimer's Does Not Start With Forgetting
The term describes variants of the same underlying disease that present through different symptoms, and they are frequently misdiagnosed for years.
The study examined four: posterior cortical atrophy, in which visual and spatial processing degrades first, so a person may struggle to judge distances, read a line of text or find an object in plain sight; logopenic variant primary progressive aphasia, in which word-finding and language break down; dysexecutive Alzheimer's disease, which affects planning and problem solving; and corticobasal syndrome, which combines cognitive changes with movement problems.
"Atypical Alzheimer's disease is often underrecognized and underrepresented in clinical trials," said study author Dror Shir of the Mayo Clinic in Jacksonville, Florida. He said the findings suggest treatment criteria may unintentionally exclude many of these patients even in early disease.
These variants tend to appear at younger ages than typical Alzheimer's, and patients frequently cycle through ophthalmologists, speech therapists or psychiatrists before receiving a neurological diagnosis. That diagnostic delay compounds the eligibility problem, because anti-amyloid therapies are given early in the disease course and time spent misdiagnosed is time the window narrows.
The Mismatch Is Between Criteria and Symptoms, Not Between Drug and Disease
This distinction is central and easy to lose.
The study assessed whether these patients would meet eligibility requirements drawn from the major clinical trials and the appropriate use recommendations developed for lecanemab and donanemab. It did not test whether the drugs work in atypical Alzheimer's, and it produced no evidence on that question either way.
That leaves the situation genuinely uncertain. These patients have the same underlying pathology, amyloid confirmed by biomarker testing, which is the target the drugs are designed to clear. But they were largely absent from the pivotal trials, so there is no efficacy or safety evidence specific to them.
Beyond cognitive screening, brain imaging findings excluded 22 to 27 percent of participants, and disease severity excluded a further 19 to 23 percent who were rated as having moderate or severe dementia. Shir said people with atypical Alzheimer's may score lower on tests of visual-spatial ability or executive function even when they are still managing daily life, and that current tools might overestimate the functional stage of the disease.
An important limitation belongs alongside that. The study was retrospective and based on existing clinical records, so researchers estimated eligibility rather than evaluating patients directly. A real-world clinic assessment could reach different conclusions for individual patients. The work was supported by the National Institutes of Health and the Alzheimer's Association.
The Practical Position Families Are Left In
For a household navigating this, the useful move is to separate what is decided from what is negotiable.
Eligibility is set by FDA labeling, by appropriate use recommendations from professional societies, and by individual health systems and insurers. A cognitive screening score is one input among several, and a clinician who documents preserved daily function may reach a different conclusion than a cutoff score alone suggests. It is reasonable to ask a neurologist directly which criterion is disqualifying and whether a more detailed functional assessment would change the picture.
Specialized centers matter here. Academic memory clinics and centers focused on atypical dementias are more likely to recognize these variants, have access to appropriate biomarker testing, and run trials that enroll them. A second opinion at such a center is a legitimate step, though travel and cost are real barriers.
Anti-amyloid therapy is also not the only thing at stake in a diagnosis. Accurate identification of a variant changes symptom management, rehabilitation referrals, driving and safety planning, disability documentation, and eligibility for other trials. Posterior cortical atrophy in particular calls for occupational therapy and low-vision strategies that a general dementia care plan would miss.
Cost and access considerations apply to the drugs themselves regardless of eligibility. These therapies require infusions, MRI monitoring for a known side effect involving brain swelling and small bleeds, and specialist follow-up. Coverage typically requires documented amyloid confirmation and registry participation, and the travel burden of repeat infusions and scans falls hardest on rural families.
What Would Change the Picture
Two things could shift this, and neither is imminent.
The first is revised eligibility criteria that account for non-memory presentations, which is what the study's authors argue for. That would require action from professional societies and potentially label changes.
The second is trial data. Studies enrolling patients with atypical Alzheimer's would establish whether these drugs help this group, which is the question nobody can currently answer. Until then, exclusion is not a judgment that treatment would fail, and inclusion would not be a guarantee that it would work.
Families should be wary of clinics offering anti-amyloid therapy outside established criteria and monitoring requirements. The safety profile of these drugs, particularly the risk of amyloid-related imaging abnormalities, is the reason the monitoring exists.
Anyone noticing progressive difficulty with reading, judging distance, finding words or planning familiar tasks should raise it with a clinician and ask specifically about referral to a memory or cognitive neurology specialist. The American Academy of Neurology maintains a patient resource on dementias for families beginning that process. This article is general information and is not a diagnosis.
Frequently Asked Questions
What did the study find? Between 70 and 85 percent of 184 people with biomarker-confirmed atypical Alzheimer's would not meet lecanemab or donanemab eligibility criteria.
Why were they excluded? Cognitive screening performance accounted for 50 to 67 percent of exclusions, imaging findings for 22 to 27 percent, and disease severity for 19 to 23 percent.
Does this mean the drugs would not work for them? No. The study assessed eligibility only. It did not test efficacy in these patients.
What is atypical Alzheimer's? Variants of the disease that begin with vision, language, executive function or movement problems rather than memory loss.
Which variants were studied? Posterior cortical atrophy, logopenic variant primary progressive aphasia, dysexecutive Alzheimer's disease, and corticobasal syndrome.
What are the study's limits? It was retrospective and used existing records, so eligibility was estimated rather than assessed in person.
What should families do? Ask the neurologist which specific criterion is disqualifying, and consider evaluation at a center specializing in atypical dementias.
