A new study suggests that certain risk factors and blood biomarkers associated with Alzheimer’s disease can be detected as early as age 24. Allison Aiello, James S. Jackson Healthy Longevity Professor of Epidemiology at Columbia University is spearheading this innovative research. It complicates our popular understanding of the age of onset of Alzheimer’s disease, which is understood as primarily affecting individuals 65 years and older. About 32 million people globally now suffer from Alzheimer’s disease, a progressive neurodegenerative disorder characterized by memory loss and cognitive decline.
The research was published in The Lancet Regional Health – Americas. To account for that, their analysis drew on data from the National Longitudinal Study of Adolescent to Adult Health. This landmark study followed individuals from their teenage years into their 30s and even 40s. It is the first to compare a range of demographic, socioeconomic, environmental, and health risk factors in younger populations (<50 years) for their impact on standard cognitive measures. In this analysis, researchers standardized ATN biomarkers—A for amyloid, T for tau, N for neurodegeneration—to determine how they’re related to cognitive decline.
Alzheimer’s disease has traditionally been diagnosed once symptoms manifest, usually after age 65. Previous research shows that Alzheimer’s biomarkers can develop many years before this diagnosis. Aiello notes the CAIDE risk score has been used in other studies. It’s been shown to have high predictive value for risk of Alzheimer’s disease, sometimes many decades before someone is diagnosed.
These results suggest cognitive measures related to cardiovascular and inflammatory risk factors. We know this association happens in adults beginning in their late 20s, indicating the role of immediate and delayed word recall and working memory. Aiello underscores the importance of this finding. As she puts it, “The evidence is increasingly clear that our health status and exposures during the early to midlife predicts Alzheimer’s disease in the older years.”
Scientists used to think that the biological processes that result in Alzheimer’s started only after the clinical disease had already begun to show up. “Alzheimer’s is a progressive, multifactorial disease. Its biological underpinnings are often underway long before symptoms ever show up,” says Jasdeep S. Hundal, a neuropsychologist with a focus on cognitive change.
The study underscores the important need for earlier detection of cognitive decline. Hundal adds, “If we wait until cognitive deficits are clinically observable—we’ve lost the critical window for effective intervention.” As he goes on to explain, methods that can detect vulnerability in advance of permanent neuronal injury are critical for real preventative power.
Aiello’s research highlights the importance of changing risk factors to delay or prevent the onset of Alzheimer’s disease. Our goal is to follow study participants over the course of their entire lives. Our hope is that early patterns can be altered by engaging in preventive behaviors and implementing strategies of intervention to lower the risk of developing Alzheimer’s disease,” Aiello says.
While results around the ATN biomarkers are promising, not much is known about these indicators in individuals under the age of 50. This significant gap in knowledge provides a challenge and opportunity for future research. Aiello says that these findings provide some of the first early evidence indicating Alzheimer’s disease is a life-long process. It seems that these structural changes may start much earlier in life than we first understood.
The researchers observed a curious interaction with genetic risk markers, namely APOE e4. Aiello noted that the relationship between this marker for genetic risk and cognition emerges later in life. He told us why this delay is thus unclear. As one possibility, researchers have proposed that effects of APOE e4 build up over time. They argue that these adverse effects are exacerbated beyond middle age due to mediation by a host of environmental and/or biological factors.
Prevention Researchers are coming to a consensus that taking a preventive neuroscience approach is very important. If adopted nationally, this approach would have a profound impact on how we age our brains. “Learning from studies like this propel the field toward preventive neuroscience,” Hundal says. Specifically, they allow us to examine the long-term effects of initiating changes to cardiovascular, metabolic and immune risk factors, target these mechanisms and alter the trajectory of brain aging.
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