Dementia after age 90

It may seem natural to assume that people experience cognitive decline after age 90, but until recently, researchers had limited evidence about how advanced age affects the brain. This major knowledge gap will need to be addressed as people live longer. By 2100, there could be around 230 million people 90 or older on Earth. As a result, scientists, clinicians and policymakers are seeking more information to help them support this expanding demographic.

Researchers at UC Davis Health and Kaiser Permanente have helped fill this knowledge gap by tracking a large group of 90+ year-olds since 2018 - the LifeAfter90 study. Their most recent findings, which were published in The Lancet Healthy Longevity, delineate dementia risk disparities between genders and racial and ethnic groups. The study also revealed how older brains respond to genetic variables.

"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 effected by dementia after 90 and how the main Alzheimer's risk gene (APOE) factors in."

LifeAfter90

LifeAfter90 participants are Kaiser Permanente members, 90 or older, who enrolled before they had any signs of dementia. Led by Whitmer, researchers have closely followed these patients, examining them every six months to track their cognitive health.

Because participants are long-term Kaiser Permanente members, the LifeAfter90 team has access to decades of health information, in some cases dating back to the 1960s. The Lancet study examined medical records from over 800 participants, median age 92. This is the first effort to investigate dementia after 90 in a highly diverse cohort.

The researchers found that, like their younger counterparts, women 90 and older are at higher risk for dementia - two-fold greater than men. There were also racial and ethnic risk disparities, similar to those of younger groups. Black participants had a 75% greater 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."

The APOE Factor

The APOE gene has long been linked to Alzheimer's disease, both positively and negatively. APOE2 is a protective variant, lowering the risk of developing Alzheimer's. APOE4 has the opposite effect, significantly increasing risk.

The study found APOE2's protective effects continue past age 90, reducing risk by 60%. And while APOE4 did not appreciably boost the risk of dementia incidence for the study group as a whole, gender and ethnicity breakdowns showed it increased the risk among men. In addition, APOE4 essentially doubled the risk among Black participants.

"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."

While the authors found these results intriguing, they caution that many questions remain. Some participants had hypertension, high cholesterol and other dementia risk factors in their 60s and 70s but stayed cognitively sound. The same was true for some with APOE4. The researchers want to understand the mechanisms that may have protected these people and perhaps find ways to replicate those advantages in others.

But in the more immediate future, the findings offer new insights into how people's brains age; information that could support better 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."

This research was supported by the National Institute on Aging of the National Institutes of Health (R01AG056519 and P30AG072972).

A full list of coauthors is available in the paper.