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Researchers of the University of California, San Diego (United States) have discovered that a new blood biomarker can predict a woman’s risk of develop dementia up to 25 years before symptoms appear.
The study, published in ‘JAMA Network Open‘, shows that higher levels of phosphorylated tau 217 (p-tau217), a protein linked to brain changes seen in Alzheimer’s disease, were strongly associated with future mild cognitive impairment and dementia in older women with cognitive health at the beginning of the study, that is, before memory or thinking problems were detected.
A clue in the blood that precedes the first oblivion decades
“Our study suggests that we could identify women with high risk of dementia decades before symptoms appear,” emphasizes Aladdin H. Shadyabfirst author of the study and associate professor of public health and medicine at UC San Diego in the Herbert Wertheim School of Public Health and Human Longevity Sciences and the Faculty of Medicine.
“This extended time frame opens the door to earlier prevention strategies and more targeted follow-up, rather than waiting until memory problems are already affecting daily life,” he says.
The findings are based on data from 2,766 participants of the Report Study of the Women’s Health Initiative, a large national study that included women ages 65 to 79 in the late 1990s and followed them for up to 25 years. All women had cognitive impairment upon entering the study.
When p-tau217 spikes, so does dementia risk
Blood samples collected at the start of the study were analyzed years later to measure p-tau217a form of tau protein that reflects brain changes early symptoms associated with Alzheimer’s disease.
Over years of follow-up, researchers identified women who developed memory or reasoning problems, including dementia. Those that presented higher levels of p-tau217 in blood at the beginning of the study had a much higher chance of developing dementia in later stages of life. In fact, as levels of this biomarker increased, so did the risk of dementia. Women with the highest levels of p-tau217 were most likely to develop long-term dementia.
However, the researchers also found that the risk of cognitive decline or dementia associated with higher levels of p-tau217 was not the same for everyone. For example, higher levels of p-tau217 were more strongly associated with worse cognitive outcomes among women over 70 years old than among those under 70 years of age at the beginning of the study and among those with the genetic risk factor APOE e4 for Alzheimer’s disease.
The study also found that p-tau217 was more predictive of dementia among women who had been randomized to hormonal therapy with estrogen plus progestin versus placebo. The strength of the association also differed between black and white women, but combining p-tau217 with age improved dementia prediction similarly in both groups.
“Blood biomarkers like p-tau217 are especially promising because they are much less invasive and potentially more accessible than brain imaging or cerebrospinal fluid testing,” says lead study author Dr. Linda K. McEvoy, senior investigator at the Kaiser Permanente Washington Health Research Institute and professor emeritus at the UC San Diego Herbert Wertheim School of Public Health. “This is important to accelerate research into the factors that influence dementia risk and to evaluate strategies that can reduce it.”
Currently, the clinical use of blood biomarkers is not recommended in people without symptoms of cognitive impairment. The authors note that additional studies are needed to determine how p-tau217 testing could be used in routine clinical care and whether early identification can significantly improve outcomes. Future research will also explore how factors such as hormone therapy, genetics, and age-related conditions interact with plasma p-tau217 across the lifespan to affect dementia risk.
“Ultimately, the goal is not just prediction,” adds Shadyab, “but use that knowledge to delay or prevent dementia altogether“.
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