People who reach their 90s without dementia might appear to have escaped much of the danger of cognitive decline. Until recently, however, scientists had relatively little evidence showing what happens to dementia risk at such advanced ages.
That gap is becoming increasingly important as lifespans rise around the world. By 2100, roughly 230 million people 90 or 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 address that question through the LifeAfter90 study, which has followed a large group of adults in their 90s since 2018. The latest findings, published in The Lancet Healthy Longevity, show 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 women tend to have higher risk, but nobody knew if that was true after 90,” said Rachel Whitmer, UC Davis Health professor of public health sciences and neurology, chief of epidemiology and senior author on the study. “We need to understand who is most affected by dementia after 90 and how the main Alzheimer’s risk gene (APOE) factors in.”
Tracking Dementia Risk After Age 90
Participants in LifeAfter90 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.
Their long history with Kaiser Permanente gives researchers access to an unusually extensive collection of medical information. For some participants, health records extend back to the 1960s. The new analysis included records from more than 800 people with a median age of 92 and represents the first study of dementia after 90 conducted in a highly diverse cohort.
The results showed that many dementia disparities seen earlier in life continue into very old age. Women age 90 and older had about twice the dementia risk of men. Researchers also identified differences among 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 tenth decade of life,” said Hilary Colbeth, a UC Davis postdoctoral scholar in public health sciences and first author on the paper. “Specifically, black and Hispanic participants had significantly higher dementia incidence rates than white and Asian participants.”
Alzheimer’s Risk Genes Still Matter
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 likelihood of developing Alzheimer’s, while APOE4 is known to increase risk.
The protective effect of APOE2 remained strong even beyond age 90. Participants carrying the variant had a 60% lower risk of dementia.
APOE4 produced a more complicated pattern. Across the study population as a whole, the variant did not substantially increase dementia incidence. When researchers examined specific groups, however, APOE4 was associated with higher risk among men. Among black participants, carrying APOE4 approximately doubled dementia risk.
“We saw evidence that APOE4 impacts males and females differently after age 90,” Colbeth said. “This has prompted us to look more closely at how APOE genotypes impact mortality among those with and without dementia by 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, during their 60s and 70s yet remained cognitively healthy decades later. Some people carrying APOE4 also reached their 90s without developing dementia.
Researchers now want to determine what protected these individuals. Understanding those biological or environmental mechanisms could eventually reveal ways to reproduce 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 extreme old age and could help clinicians provide more informed care.
“Doctors need to know that certain groups are at higher or lower risk,” Whitmer said. “We can’t just assume that someone from a high-risk group makes it to 90 without dementia and they’re in the clear. 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).