Blood Biomarker Predicts Women’s Dementia Risk Up to 25 Years Early

Researchers headed by a team at the University of California San Diego have found that a novel blood-based biomarker can predict a woman’s risk of developing dementia as many as 25 years before symptoms appear. The study, involving more than 2500 women, showed that higher levels of phosphorylated tau 217 (ptau217)—a form of tau protein that reflects early brain changes associated with Alzheimer’s disease—were strongly associated with future mild cognitive impairment (MCI) and dementia among older women who were cognitively healthy at the start of the study, before any memory or thinking problems were detected.

“Our study suggests we may be able to identify women at elevated risk for dementia decades before symptoms emerge,” said Aladdin H. Shadyab, PhD, MPH, UC San Diego associate professor of public health and medicine at the Herbert Wertheim School of Public Health and Human Longevity Science and the School of Medicine. “That kind of long lead time opens the door to earlier prevention strategies and more targeted monitoring, rather than waiting until memory problems are already affecting daily life.”

Shadyab is first author of the team’s published paper in JAMA Network Open, titled “Plasma Phosphorylated Tau 217 and Incident Mild Cognitive Impairment and Dementia in Older Women,” in which they concluded, “Overall, our results support the value of plasma p-tau217 as an easily measured biomarker for future MCI or dementia that may have a variety of uses in both research and clinical practice among diverse populations.”

Plasma biomarkers of Alzheimer disease (AD) offer a minimally invasive, accessible approach for detecting AD pathology, the authors wrote. “Plasma phosphorylated tau 217 (p-tau217) has demonstrated higher accuracy in detecting AD pathology relative to other biomarkers, 2-5 with equivalent performance as cerebrospinal fluid p-tau217 for AD diagnosis.” However, they continued, “There is limited research on the long-term associations of plasma phosphorylated tau 217 (p-tau217) with mild cognitive impairment (MCI) and dementia. No study has evaluated whether such associations vary by race or hormone therapy (HT) use.”

For their reported study the team examined data from 2,766 participants in the Women’s Health Initiative Memory Study (WHIMS), a large national study that enrolled women aged 65 to 79 years in the late 1990s, and followed them for up to 25 years. All women were cognitively unimpaired when they entered the study. Blood samples collected at baseline were analyzed years later to measure p-tau217. They aimed to examine associations of baseline plasma p-tau217 with incident MCI and dementia, and determine whether associations vary by age, race, hormone use, or whether they were carriers of APOE ε4, a genetic risk factor for AD.

Over the years of follow-up, researchers identified women who developed memory or thinking problems, including dementia. Those who had higher levels of p-tau217 in their blood at the start of the study were much more likely to develop dementia later in life. In fact, as levels of this biomarker increased, so did dementia risk. Women with the highest p-tau217 levels faced the greatest likelihood of developing dementia over the long term.

However, the researchers also found that risk of cognitive impairment or dementia associated with higher levels of p-tau217 was not the same for everyone. For example, higher p-tau217 levels were more strongly associated with poorer cognitive outcomes among women over age 70 than those younger than 70 years at baseline and among those with the APOE ε4.

The study also found that p-tau217 was more predictive of dementia among women who had been randomized to estrogen plus progestin hormone therapy versus placebo. The strength of the association also differed between White and Black women, but combining ptau217 with age improved dementia prediction similarly in both groups.

“In this cohort study of cognitively unimpaired older women, p-tau217 was associated with incident MCI or dementia up to 25 years later,” the authors stated in conclusion. “These findings suggest that age, race, APOE ε4, and HT use should be considered when examining associations of p-tau217 with cognitive outcomes.”

Senior author Linda K. McEvoy, PhD, senior investigator at Kaiser Permanente Washington Health Research Institute and professor emeritus at the Herbert Wertheim School of Public Health, said, “Blood-based biomarkers like p-tau217 are especially promising because they are far less invasive and potentially more accessible than brain imaging or spinal fluid tests. This is important for accelerating research into the factors that affect risk of dementia and for evaluating strategies that may reduce risk.”

Currently, blood-based biomarkers are not recommended for clinical use in people without symptoms of cognitive impairment. The authors note that additional studies are needed to determine how p-tau217 testing might be used in routine clinical care and whether early identification can meaningfully change outcomes.

Future research will also explore how factors such as hormone therapy, genetics and age-related health conditions interact with plasma p-tau217 over the course of someone’s life to affect dementia risk. “These findings underscore the value of p-tau217 and show that many factors should be considered when examining its associations with cognitive outcomes,” they stated. “Ultimately, the goal is not just prediction,” Shadyab added, “but using that knowledge to delay or prevent dementia altogether.