Lancet
Blood test may detect early Alzheimer's changes in midlife
Clinical takeaway: Blood tests for amyloid and tau are not ready for screening dementia-free adults, but the findings suggest they could one day help target modifiable risk factors in those at highest risk.
Alzheimer's pathology builds for years before symptoms appear, but most blood-biomarker research has focused on older adults with cognitive complaints. Whether these markers track with subtle cognitive differences in midlife had been largely untested.
Among 1,350 dementia-free adults, those who tested positive for Alzheimer's neuropathology scored lower on two cognitive domains: processing speed, the ability to respond quickly to changing information, and executive function, which covers planning, focus, and adapting to new tasks. There was no link to global cognition or verbal fluency.
Biomarker-positive participants had also declined faster on verbal memory and processing speed over the five years leading up to the test, with roughly two to four times the odds of a drop markedly steeper than the cohort average. Because the blood markers were measured at the end of that window, the study ties them to decline that had already occurred rather than predicting future loss. Only about 6% of participants were biomarker-positive.
Participants were long-term enrollees in CARDIA, a multisite US cohort study originally launched to track cardiovascular risk from young adulthood. The biomarker sample was drawn at the year 35 visit; participants were aged 53 to 69. Cognition was tested at years 30 and 35. Plasma amyloid and p-tau217 were measured and scored against amyloid PET-validated cutoff points to define neuropathology positivity.
The tests are FDA-cleared only for symptomatic patients, and a positive result in a healthy 55-year-old carries real risk of a false alarm. The clearest near-term use is risk stratification: identifying people who might benefit most from addressing modifiable factors such as physical inactivity, smoking, poor sleep, and untreated hearing loss.
Effective dementia risk reduction will likely require targeting at-risk individuals before symptoms begin, whether through lifestyle and vascular interventions or anti-amyloid drugs now approved for early symptomatic disease.
Associations appeared stronger among women, Black participants, and APOE ε4 carriers, but the authors call this effect modification inconsistent, so it is exploratory rather than a basis for targeting specific groups. And the test's reach is narrow.
"There's a possibility of false positives and they can only be used for Alzheimer's, not other dementias, meaning about 60% to 70% of all dementia cases," said Kristine Yaffe, MD, vice chair in the UCSF Department of Psychiatry and Behavioral Sciences. "But for some people who discover they have the biomarkers, testing could open a window to embark on interventions that may postpone Alzheimer's onset."
Source: Jiang X. Lancet. 2026 May 30. Alzheimer's disease neuropathology plasma biomarkers and cognition in midlife: a community-based cohort study