It may be possible to detect Alzheimer's risk sooner—as early as your 20s

National Geographic

2 days ago

The accumulation of neurofibrillary tangles—like those illustrated here inside a neuron—is closely associated with cognitive decline caused by Alzheimer's disease. A recent study found that several biomarkers implicated in Alzheimer's are associated with cognitive decline as early as ages 24 to 44. Illustration by Hybrid Medical Animation, Science Photo Library
Treating the neurodegenerative disease in its earlier stages is key to slowing cognitive decline. A new study offers hope for the future.
More than a century ago, a German neuroanatomist noticed his patient acting inordinately confused. After she died, Alois Alzheimer examined her brain and discovered amyloid-beta plaques and neurofibrillary 'tangles,' two key characteristics for what we now call Alzheimer's disease.
Today we know when these plaques and tangles interfere with our normal brain functions, our neurons die. People start to forget, lose their memory. When Alzheimer's enters the later stages, it's irreversible. However, the damage may be slowed if caught early.
Now a new study cautiously suggests it may be possible to detect signs of Alzheimer's risk even earlier than previously thought possible—in a person's 20s or 30s. Given the number of Americans with Alzheimer's is projected to double to 14 million by 2060, this could be a gamechanger.
'A neuron dead is a neuron gone…forever. You want to do preventive medicine,' says Lilian Calderón-Garcidueñas, a professor at the University of Montana in the Biomedical and Pharmaceutical Sciences Department, who was not involved with the new study but says its findings coincide with her team's research into early Alzheimer's detection.
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'The key is the age group: young adults,' Calderón-Garcidueñas says. 'Most researchers in the U.S.A. are focused on elderly populations.'
Scientists have made leaps and bounds to diagnose Alzheimer's accurately and faster. After all, it wasn't until the 2000s that the disease could be diagnosed before death. Now it's generally accepted that brains demonstrate signs of Alzheimer's decades before symptoms emerge—a timeline that this research would push back even further.
'It kind of clicked for me that we really do need to be studying this earlier,' says Columbia University professor of epidemiology Allison Aiello, the new study's lead investigator. 'We did see some associations at these early levels. I was pretty surprised myself.' Why is Alzheimer's so hard to diagnose in younger brains?
Today, diagnosis and risk detection typically hinges upon finding a core biomarker like neurofibrillary tau tangles and amyloid-beta plaques. That alone doesn't guarantee a person will become symptomatic, so clinicians also look for evidence of cognitive decline. Certain standard assessments—for example, having a person recall words from a list—can measure cognition.
Additionally, there are multiple underlying causes and risk factors that can vary from person to person. To further evaluate dementia risk, clinicians use tools like Cardiovascular Risk Factors, Aging and Incidence of Dementia (CAIDE), which takes into account risk factors like body mass index, age, and education and grants a 'risk score.' Higher CAIDE scores point to higher risk.
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Because Alzheimer's primarily manifests in those 65 and older, there's historically been 'skepticism in the field [about] measuring cognitive function earlier in life,' Aiello says, especially before mid-life.
But Aiello was curious and saw her opportunity to study the issue when she joined the National Longitudinal Study of Adolescent to Adult Health. This landmark study originally enrolled 20,000 middle-schoolers and high-schoolers in 1994 and 1995 and is still ongoing—making it one of the largest longitudinal studies in the U.S.
In 2008, when participants were 24 to 34 years old, Aiello's team conducted thousands of tests, including assessing 11,500 participants' cognition and taking 4,500 blood samples. Approximately a decade later, the team again administered cognitive and genetic tests.
The findings revealed early signs of cognitive decline by age 24, and some neurodegeneration biological risk indicators among people in their 30s. Specifically, researchers analyzed interleukin 6 and interleukin 8, biomarkers of inflammation, within the blood samples. When participants were aged 34 to 44, these biomarkers were associated with lower scores on the cognitive tests. The team also found higher CAIDE risk scores were associated with lower cognitive scores as early as during someone's mid-20s—decades earlier than mid-life, when risk factors are typically tested.
'The study is a big success,' says Tatjana Rundek, director of the Evelyn F. McKnight Brain Institute at the University of Miami, who was not involved with the study. While effect size is small and associations are subtle, it still provides 'compelling molecular support for early neuroinflammation and neurodegeneration.' Study limitations
However, some experts are more cautious.
Despite its validation, Rundek says CAIDE isn't a sure-fire predictor of Alzheimer's disease, especially regarding diverse populations.
Meanwhile, some of the biomarkers found are not exclusive to Alzheimer's, says Sharon Sha, a neurology professor and the chief of Stanford University's Memory Disorders Division.
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Sha points out that the study measured 'total tau' instead of phosphorylated tau; while total tau can be an indicator of neurodegeneration, growing research finds phosphorylated tau to be more predictive of Alzheimer's specifically.
Still, she says, 'I do find that the results they found are potentially risk factors for future cognitive decline, or cardiovascular and vascular cognitive impairment risk.'
The data collection is also impressive, Sha adds. Conducting these studies is difficult because obtaining confirmatory data is costly and takes decades. 'It's hard to follow someone in their 20s, to say, their 60s or 80s, [to see] if they get a diagnosis of Alzheimer's disease.'
Aiello also agreed more research needs to be done, and that's likely coming. Other scientists in the U.K. have conducted life course studies, Aiello says, and 'I think we'll see more of these types of studies in the future.'
Her own team is continuing to follow this cohort to see how Alzheimer's risk changes over time. As participants enter the latest wave, when they are between the ages of 39 to 49, they'll take cognitive tests and measure physical and sensory functions like hearing or grip strength. The data is scheduled for analysis with results potentially forthcoming in 2026.
Early detection can empower people. Those at greater risk can start changing their lifestyles—and some healthy interventions may prevent or slow up to 40 percent of dementia cases. Current Alzheimer's therapies like lecanemab also slow decline, though in milder stages. 'The earlier the better, right?' Aiello says.
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Consequently, early detection remains a hot research topic. In 2023, researchers published a study cautiously suggesting the eyes have potential for early Alzheimer's risk prediction. Another 2024 study published in Nature Aging showed an AI-trained model could predict Alzheimer's seven years before symptoms emerged, and identified surprising patterns and risk factors.
The model suggested that osteoporosis may be an Alzheimer's risk factor for women. While this doesn't mean a woman with osteoporosis will definitely develop Alzheimer's, 'we see these relationships,' says Alice Tang, an MD/Ph.D. candidate at University of California, San Francisco, who led the study. 'And so that has led to a lot more questions being opened up and better studies down the line.'
Ultimately, research avenues like these may soon be able to help scientists develop a more meaningful model for early Alzheimer's prediction. In her own work, Aiello is excited to see what Wave VI reveals. 'I think it's going to be really exciting for people to try to tease apart some of these associations much earlier in life, in a really kind of in-depth way.'