Researchers have identified a potential early warning sign of Alzheimer’s disease in middle-aged adults experiencing subtle concerns about their memory and thinking.
Adults as young as 45 who expressed concerns about their memory or thinking had elevated levels of a blood biomarker associated with Alzheimer’s disease, even though brain scans showed no detectable structural changes. The findings from the University of Otago suggest that biological signals linked to Alzheimer’s may emerge long before conventional imaging can identify abnormalities.
Researchers analyzed data from the Dunedin Multidisciplinary Health and Development Study, focusing on a blood plasma biomarker called pTau181, which has been strongly associated with Alzheimer’s disease in older adults. At age 45, participants reported concerns about their cognitive health, completed detailed cognitive assessments, and underwent MRI scans. Their biological aging was also assessed using DunedinPACE.
Alzheimer’s-Related Changes May Begin Decades Earlier
Lead author Dr. Ashleigh Barrett-Young, from the University of Otago’s Department of Psychology, says the findings add to evidence that processes associated with Alzheimer’s may begin decades before clinical symptoms become apparent.
“This means there may be an important window for prevention, which remains one of the most promising approaches for Alzheimer’s disease,” she says.
Although higher pTau181 levels were associated with self-reported cognitive concerns, researchers found no detectable changes in brain structure. The results raise the possibility that subtle cognitive changes could emerge before they become measurable through standard assessments. However, further research is needed to determine whether these early signals predict subsequent cognitive decline.
“This highlights the need for careful research to understand how early changes relate to later outcomes.”
Blood Biomarkers Offer Promise, but Important Questions Remain
Blood tests that detect Alzheimer’s-related biomarkers could eventually make early identification more accessible. However, such tests are not yet available for routine clinical use in Aotearoa New Zealand, and scientists still need to establish what elevated pTau181 levels mean for otherwise healthy middle-aged adults.
“Understanding the earliest stages of disease development is essential for designing effective prevention and treatment strategies, even if clinical tools are still some way off,” Dr. Barrett-Young says.
“Importantly, biomarkers like pTau181 reflect risk, not certainty.”
An elevated reading does not establish that someone has Alzheimer’s disease or will develop it. Long-term follow-up will be necessary to determine how these blood measurements relate to future cognitive health.
A Long-Running Study Tracks the Biology of Aging
The research draws on the Dunedin Study, which has followed participants across decades to investigate how health and aging develop throughout life. With the age 52 assessment now complete, researchers have additional opportunities to examine how earlier biological measurements relate to changes in middle age and beyond.
Dunedin Study Director Professor Moana Theodore credits Dr. Barrett-Young’s leadership and the contributions of New Zealand researchers to international aging research.
“Following the recently completed and highly successful age 52 assessment, we are entering the next stage of the research with momentum,” she says.
“The University of Otago Dunedin Study continues to inform global aging policy by demonstrating aging as a lifelong process allowing for better targeting of preventative healthcare.”
Professor Theodore also emphasizes the commitment of participants, who continue to provide personal health information despite the uncertainty surrounding emerging biomarkers. Individual pTau181 results are not shared because the test remains a research tool and its long-term implications are not yet understood.
“They take part to support future generations, knowing that this biomarker is still at an early, research-only stage and that individual results are not shared because scientists do not yet understand the long-term outcomes.
“Many have seen first-hand the multiple ways dementia can affect families and hope that the information that they provide will be used to reduce disease and help others.”
Reference: “Plasma pTau181 is associated with subjective cognitive concerns but not objective cognitive decline or structural brain integrity measures in midlife” by Ashleigh Barrett-Young, Erin E. Cawston, Brigid Ryan, Wickliffe C. Abraham, Antony Ambler, Tim Anderson, Kirsten Cheyne, Elizabeth Goodin, Sean Hogan, Renate M. Houts, David Ireland, Annchen R. Knodt, Jesse Kokaua, Tracy R. Melzer, Sandhya Ramrakha, Karen Sugden, Benjamin Williams, Phillipa Wilson, Avshalom Caspi, Ahmad R. Hariri, Terrie E. Moffitt, Richie Poulton and Reremoana Theodore, 8 May 2026, GeroScience.
DOI: 10.1007/s11357-026-02282-z
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