A Lancet Neurology review addresses people who are cognitively unimpaired but have biomarker evidence of Alzheimer's disease neuropathological change. Anti-amyloid antibodies are approved for symptomatic early Alzheimer's disease, and trial data hint that people with less pathology may benefit most, so prevention trials are now testing them in this pre-symptomatic group.
The authors set out what would need to be in place before testing and treating such people becomes routine. Biomarker tests perform worse when the condition is uncommon in the tested population, and intermediate results may be false positives. A positive result carries ethical, psychological and insurance consequences, and the effects on health systems — scans, infusions, monitoring for amyloid-related imaging abnormalities — would be large.
No treatment is yet proven for cognitively unimpaired people. The review's value is as a framework for the conversations neurologists are already having with worried, well people who have read about blood tests.
- No anti-amyloid therapy is proven or approved for cognitively unimpaired people.
- Blood biomarker tests are less reliable where Alzheimer's pathology is uncommon in those tested.
- Intermediate biomarker results may not reflect true pathology; avoid labelling on a single borderline value.
- Discuss the personal and practical consequences of a positive result before ordering a test in a symptom-free person.
Why it matters
Biomarker testing is reaching the worried well faster than any treatment that would help them.
Don't overread it
This is a review of open questions; it does not recommend screening or treating cognitively unimpaired people.
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