Estimating cognitive impairment risk, timing

October 7, 2026

Estimating cognitive impairment risk, timing

At a Glance

  • Combining blood p-tau217 levels together with APOE4 gene status improved predictions of dementia risk.
  • The findings may help doctors better assess patients’ risk for cognitive impairment and estimate when symptoms may develop.
Illustration of human brain and enlarged DNA strands
The study found having high blood levels of a protein called p-tau217 increases the risk for cognitive impairment more in people with the APOE-ε4 gene.
whiteMocca / Shutterstock

Measurements of certain indicators called biomarkers can provide information about the risk and timing of dementia. For example, people are more likely to develop Alzheimer’s disease if they have more of a protein called p-tau217 in their blood. p-tau217 is a biomarker of protein changes in the brain linked with Alzheimer’s.  

Some of the best understood gene variants that affect the risk of developing Alzheimer’s disease are in the APOE gene. People who have a form called APOE-ε4 are known to have an increased risk of developing Alzheimer’s disease. Genetic testing for APOE status combined with biomarker testing might be more useful for assessing dementia risk than either one alone.  

A team of NIH-funded researchers led by Dr. Richard Mayeux of Columbia University examined the links among blood levels of p-tau217, different forms of the APOE gene, and dementia risk in more than 8,500 older adults at risk for or living with cognitive impairment. The results were published in Lancet Neurology on September 9, 2026. 

The researchers pooled data from seven different studies, including several funded by NIH. They included data from participants in Canada, Dominican Republic, and the United States. Data were collected from 1992 to 2025.  

The team found blood levels of p-tau217 were higher in people with cognitive impairment. This includes mild cognitive impairment as well as dementia, which involves more severe thinking and memory problems. Levels of p-tau217 were also higher in those who were initially healthy but developed cognitive impairment later.

People with high p-tau217 and the APOE-ε4 gene were especially likely to have cognitive impairment or develop it later. These links were stronger in non-Hispanic White participants than in people from other racial or ethnic backgrounds. Previous studies have shown the risk conferred by APOE-ε4 can vary based on ancestry.

The time to cognitive impairment with increasing p-tau217 decreased almost twice as fast in APOE-ε4 carriers as in non-carriers. The researchers observed a three- to four-year window between APOE-ε4 carriers showing elevated p-tau217 levels and symptoms becoming apparent.

The new study suggests that having high blood levels of p-tau217 increases the risk for cognitive impairment more in people with the APOE-ε4 gene. Combining blood biomarker and genetic tests could help doctors identify people at high risk for Alzheimer’s disease and estimate the timing of future symptoms. It could also help researchers refine clinical trials designed to prevent dementia.

“The combination of the tests really makes a difference in predictive power,” Mayeux says. “What this will allow us to do is make better predictions about the onset of symptoms in people at risk, and when preventative drugs become available, prescribe those at the right time.”

—by Brandon Levy

Related Links

References

Plasma phosphorylated tau 217 concentrations, APOE genotype, and timing of cognitive impairment in individuals across diverse racial and ethnic groups: a pooled analysis of prospective cohort studies. Xu Y, Gunasekaran TI, Gu Y, Reyes-Dumeyer D, Piriz A, Sanchez D, Mejia DR, Medrano M, Lantigua RA; Alzheimer's Disease Neuroimaging Initiative; Honig L, Wilson R, Reyes RER, Manly JJ, Brickman AM, Engelman CD, Johnson S, Asthana S, Bennett DA, Petersen M, O'Bryant S, Vardarajan BN, Mayeux R. Lancet Neurol. 2026 Sep 9:S1474-4422(26)00313-3. doi: 10.1016/S1474-4422(26)00313-3. Epub ahead of print. PMID: 42716078.

Funding

NIH’s National Institute on Aging (NIA).