Alzheimer’s Blood Biomarkers in Midlife

A US community-based study found that middle-aged adults with blood biomarkers indicating Alzheimer’s disease neuropathology already showed worse cognition and faster cognitive decline years before dementia diagnosis. Researchers analyzed 1,350 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study who underwent plasma biomarker testing at year 35 (2020–2022). The average participant age was 61 years, 58% were women, 45% were Black, and all participants were free of probable dementia. Investigators measured plasma amyloid-β42 (Aβ42), amyloid-β40 (Aβ40), phosphorylated tau217 (p-tau217), and biomarker ratios including p-tau217/Aβ42 and Aβ42/40, using PET-validated cutoffs to classify Alzheimer’s neuropathology status as negative, intermediate, or positive. Alzheimer’s pathology positivity was identified in 6% of participants using p-tau217/Aβ42, 15% using Aβ42/40, and 4% using p-tau217 alone. Compared with biomarker-negative individuals, participants with positive biomarker profiles performed significantly worse on tests of processing speed and executive function. In addition, biomarker positivity was linked to markedly greater odds of accelerated 5-year cognitive decline, particularly in verbal memory and processing speed. For example, individuals positive for Aβ42/40 had more than fourfold higher odds of accelerated verbal memory decline, while those positive for p-tau217 had nearly fourfold higher odds of accelerated decline in processing speed. No significant associations were observed for global cognition or verbal fluency. Although findings were not entirely consistent across analyses, some associations appeared stronger among women, Black participants, and APOE ε4 carriers. The study highlights that Alzheimer’s-related brain pathology can already be detectable in midlife through simple blood tests and may identify individuals who could benefit from earlier prevention, lifestyle interventions, and future disease-modifying therapies before clinical dementia develops. Source: https://www.thelancet.com/