Making it to 90 without dementia might seem like proof that someone has escaped one of the biggest threats associated with aging.
But new research suggests the risk does not simply disappear with the passing years.
In a study of 805 adults aged 90 and older who did not have dementia when they entered the LifeAfter90 study, 138 developed dementia during an average two-year follow-up. The findings suggest that even people who reach exceptional old age with their thinking and memory intact can still develop the condition.
Yet the study also revealed something more complicated. Dementia risk varied between groups, and one version of a gene associated with Alzheimer's disease appeared protective. Meanwhile, separate research from the same LifeAfter90 project has found that some people can have substantial changes in their brains while remaining cognitively healthy.
Together, the findings raise a fascinating question: What allows some aging brains to keep functioning despite the changes that can lead to dementia?
Dementia Risk Does Not Stop At 90
Researchers have relatively little data on dementia in people over 90 compared with younger older adults.
The LifeAfter90 study was designed to help fill that gap. Participants from Kaiser Permanente Northern California were at least 90 years old and underwent clinical evaluations roughly every six months between 2018 and 2024.
For the latest analysis, researchers excluded people who already had dementia and those who had only completed one assessment, leaving 805 participants. Their median age was 92, and the group included people from several racial and ethnic backgrounds.
During follow-up, 17% developed dementia.
At the same time, 37% died, which is important when studying people in their 90s. Researchers therefore accounted for death when estimating dementia risk, rather than treating it as though every participant remained available to develop the condition.
The resulting age-standardized incidence was about 117 new dementia cases per 1,000 person-years. In other words, the risk remained substantial even among people who had already reached 90 without dementia.
Women And Black Participants Had Higher Risk
The researchers then looked at whether dementia risk differed according to sex and race or ethnicity.
It did.
Women had an estimated 89% higher risk of developing dementia than men in the study. Black participants also had a higher risk than Asian participants. The researchers said these findings suggest that differences in dementia risk seen earlier in life may continue into the oldest ages.
The result is important because reaching 90 without dementia could otherwise be viewed as a kind of biological finish line.
It isn't.
Instead, people appear to arrive at very old age with different combinations of genetic and biological factors that continue to influence what happens to their brains.
One of those factors is a gene that has received considerable attention in Alzheimer's research.
One APOE Variant Appeared Protective
The researchers examined APOE, a gene involved in transporting fats in the body and one of the best-known genetic factors linked to Alzheimer's disease.
The gene comes in several versions. APOE ε4 is associated with a higher risk of Alzheimer's disease at younger ages, while APOE ε2 has generally been associated with lower risk.
Among the 413 participants who had genetic data available, those carrying APOE ε2 had a significantly lower risk of dementia than people without the variant. Their estimated risk was about 61% lower.
The findings for APOE ε4 were less clear.
Researchers did not find a statistically significant increase in dementia risk among ε4 carriers compared with non-carriers in the overall group. The study suggested that the relationship could differ by sex, but the researchers cautioned that more work is needed to understand the pattern.
That uncertainty is important. The results do not mean APOE ε4 stops mattering after 90. They suggest that the way genetic risk operates in people who reach extreme old age may be more complicated than it is in younger populations.
And genetics may be only part of the story.
Some Brains Stay Sharp Despite Significant Changes
A separate LifeAfter90 study offers an intriguing piece of that puzzle.
Researchers examined the brains of 124 people aged 90 and older after their deaths. At their final cognitive assessment, 41% had normal cognition, even though many had abnormalities in their brains associated with aging and neurodegenerative disease.
The researchers found that 69% of the participants had three or more types of neuropathology, meaning physical changes in brain tissue that can be associated with neurological disease.
Yet substantial pathology did not always translate into obvious cognitive problems.
Among people who had normal cognition at their final assessment, 59% had three or more neuropathological findings. The researchers described these individuals as potentially representing cognitive resilience, meaning an apparent ability to maintain normal thinking despite a significant burden of brain pathology.
That does not mean the brain changes were harmless. Alzheimer's disease pathology was still the finding most strongly associated with cognitive impairment in the study.
Instead, the results suggest that the amount of pathology in an aging brain and the symptoms a person experiences are not always perfectly matched.
What Protects A Resilient Brain?
That mismatch is now one of the most interesting questions surrounding extreme aging.
Why can one person accumulate several types of brain pathology yet remain cognitively normal, while another develops noticeable impairment?
The LifeAfter90 studies do not provide a single answer. The latest dementia analysis points to differences in sex, race and genetics, while the brain-autopsy research suggests that some people may be better able to tolerate neurological changes without losing cognitive function.
There may be several reasons for that resilience, but researchers still need to determine which biological mechanisms are actually responsible.
For now, one thing is becoming clearer: reaching 90 without dementia is not the end of the story.
Some people will still develop dementia in their 90s, while others may maintain remarkably strong cognitive abilities despite changes accumulating inside their brains.
Understanding why those paths diverge could eventually tell scientists something just as valuable as knowing what causes dementia: what helps the aging brain withstand it.
