People who reach their 90s without developing dementia may seem to have avoided many of the known risk factors for cognitive decline. However, researchers have only recently begun to understand how dementia risk changes after age 90.
This research is becoming increasingly important as people live longer worldwide. By 2100, an estimated 230 million people may be living beyond age 90, creating an urgent need for more information about brain health, cognitive aging, and dementia risk in this rapidly growing population.
Researchers from UC Davis Health and Kaiser Permanente have been tracking a large group of adults in their 90s through the LifeAfter90 research study since 2018. The latest findings, published in The Lancet Healthy Longevity, reveal important differences in dementia risk based on sex, race, ethnicity, and genetics.
“We know from studies of adults age 65 and older that dementia rates differ between groups and that women tend to face a higher risk. However, it was not known whether those differences continued after age 90,” said Rachel Whitmer, professor of public health sciences and neurology, chief of epidemiology at UC Davis Health, and senior author of the study. “We need to understand who is most affected by dementia after age 90 and how the key Alzheimer’s disease risk gene, APOE, influences that risk.”
Tracking dementia risk after age 90
LifeAfter90 participants are Kaiser Permanente members who were at least 90 years old and had no signs of dementia when they joined the study. Under Whitmer’s leadership, researchers evaluate participants every six months to monitor changes in memory, thinking, and overall cognitive health.
Kaiser Permanente’s long history of maintaining comprehensive medical records gives researchers access to an extensive collection of health information. Some participants’ records date back to the 1960s. The new analysis included more than 800 adults with a median age of 92, making it the first study of dementia risk after age 90 to examine a highly diverse population.
The findings showed that many dementia disparities seen earlier in life continue into very old age. Women over 90 had approximately 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 surprising that the racial and ethnic differences in dementia risk observed earlier in life persist into the 10th decade,” said Hilary Corbes, a postdoctoral fellow in public health sciences at the University of California, Davis, and lead author of the study. “In particular, Black and Hispanic participants had significantly higher rates of dementia than White and Asian participants.”
Alzheimer’s disease risk genes remain important
The researchers also examined APOE, a gene strongly associated with Alzheimer’s disease and dementia. Different APOE variants can affect risk in opposite ways. APOE2 is generally considered protective and is linked to a lower likelihood of developing Alzheimer’s disease, while APOE4 is associated with increased risk.
The protective effect of APOE2 remained significant after age 90. Participants who carried the variant had a 60% lower risk of developing dementia.
APOE4 was associated with more complex results. Across the entire study population, the variant did not significantly increase dementia incidence. However, further analysis showed that APOE4 was linked to higher dementia risk among men. Among Black participants, carrying APOE4 was associated with approximately twice the risk of dementia.
“We found evidence that APOE4 affects men and women differently after age 90,” Corbes said. “This led us to examine more closely how APOE genotype influences survival to age 90 among people with and without dementia.”
Why some people remain cognitively healthy
The findings also highlight an important unanswered question: Why do some people remain cognitively healthy despite having dementia risk factors? Some participants had conditions such as high blood pressure and high cholesterol during their 60s and 70s but remained free of dementia decades later. Others carried APOE4 yet reached their 90s without developing cognitive impairment.
Researchers now hope to identify the biological, genetic, and environmental factors that protected these individuals. Understanding these mechanisms could eventually lead to strategies that help reduce dementia risk in other people.
For now, the study provides a clearer picture of how dementia risk affects adults in their 90s and may help doctors offer more personalized care and prevention guidance.
“Doctors need to know whether certain groups face a higher or lower risk of dementia after age 90,” Whitmer said. “We cannot assume that people in high-risk groups who survive to age 90 are automatically protected. Dementia risk reduction should be discussed with everyone.”
This research was supported by the National Institute on Aging of the National Institutes of Health through grants R01AG056519 and P30AG072972.
Source: www.sciencedaily.com