It might seem that people who reach age 90 without dementia have escaped much of the danger of cognitive decline. However, until recently scientists had relatively little evidence to show what happens to dementia risk at such advanced ages.
That gap is becoming increasingly important as life expectancy increases around the world. By 2100, approximately 230 million people aged 90 and older could be alive worldwide, increasing the need for better information about how the brain ages in this rapidly growing population.
Researchers at UC Davis Health and Kaiser Permanente are helping to address that question through the LifeAfter90 Studiowhich has followed a large group of 90-year-old adults since 2018. The latest findings, published in The Lancet Healthy Longevityshow notable differences in dementia risk by sex, race, ethnicity, and genetics.
“We know from other studies, done in people 65 and older, that there are differences in dementia rates, and that women tend to be at higher risk, but no one knew if that was true after age 90,” said Rachel Whitmer, professor of public health sciences and neurology at UC Davis Health, chief of epidemiology and senior author of the study. “We need to understand who is most affected by dementia after age 90 and how the main Alzheimer’s risk gene (APOE) is involved.”
Monitoring dementia risk after age 90
LifeAfter90 participants are Kaiser Permanente members who were at least 90 years old and showed no signs of dementia when they enrolled. Under Whitmer’s leadership, researchers evaluate participants every six months to monitor changes in cognitive health.
His long history with Kaiser Permanente gives researchers access to an unusually extensive collection of medical information. For some participants, health records date back to the 1960s. The new analysis included records from more than 800 people with an average age of 92 and represents the first study of dementia after age 90 conducted in a highly diverse cohort.
The results showed that many disparities in dementia seen earlier in life continue into very old age. Women aged 90 and older had about twice the risk of dementia as men. The researchers also identified differences between racial and ethnic groups, with Black participants facing a 75% higher risk than Asian participants.
“It is striking that the racial and ethnic disparities in dementia risk observed in younger adults continue into the 10th decade of life,” said Hilary Colbeth, a postdoctoral fellow in public health sciences at UC Davis and first author of the paper. “Specifically, black and Hispanic participants had significantly higher dementia incidence rates than white and Asian participants.”
Alzheimer’s risk genes remain important
The researchers also examined the role of APOE, a gene strongly associated with Alzheimer’s disease. Different versions of the gene can influence risk in opposite directions. APOE2 is considered protective and is associated with a lower chance of developing Alzheimer’s, while APOE4 is known to increase the risk.
The protective effect of APOE2 remained strong even after age 90. Participants carrying the variant had a 60% lower risk of dementia.
APOE4 produced a more complicated pattern. In the entire study population, the variant did not substantially increase the incidence of dementia. However, when researchers examined specific groups, APOE4 was associated with an increased risk among men. Among black participants, carrying APOE4 approximately doubled the risk of dementia.
“We saw evidence that APOE4 affects men and women differently after age 90,” Colbeth said. “This has led us to take a closer look at how APOE genotypes impact mortality among those with and without dementia at age 90.”
Why some people remain cognitively healthy
The findings also highlight an important mystery. Some participants had well-established dementia risk factors, including hypertension and high cholesterol, in their 60s and 70s, but remained cognitively healthy decades later. Some APOE4 carriers also lived to be 90 years old without developing dementia.
Researchers now want to determine what protected these individuals. Understanding those biological or environmental mechanisms could eventually reveal ways to replicate some of the same protective effects in other people.
For now, the study provides a clearer picture of how dementia risk continues to operate in older people and could help doctors provide more informed care.
“Doctors need to know if certain groups are at higher or lower risk,” Whitmer said. “We can’t just assume that someone in a high-risk group reaches age 90 without dementia and is safe. We need to talk about risk reduction for everyone.”
The research was supported by the National Institute on Aging of the National Institutes of Health (R01AG056519 and P30AG072972).