Cognitive function was found to be associated with established risk factors and biomarkers as early as age 24.
A new study led by researchers at Columbia University’s Mailman School of Public Health and the Columbia Butler Aging Center reveals that risk factors and biological markers linked to Alzheimer’s disease may influence cognitive function much earlier in life than previously thought. The research found significant associations between cognitive performance and Alzheimer’s-related risk factors in individuals as young as 24 to 44 years old, emphasizing the need for early intervention and prevention strategies.
This is the first large-scale study in the United States to systematically investigate Alzheimer’s disease risk factors, including biomarkers of cognitive decline, in a generally healthy, middle-aged population. The findings are published in The Lancet Regional Health – Americas.
“Previously, research on Alzheimer’s disease risk factors has focused on individuals aged 50 and older,” said Allison Aiello, PhD, James S. Jackson Healthy Longevity Professor of Epidemiology in the Butler Aging Center and Columbia Mailman School. “The potential impact of our findings is substantial, offering clinicians and health researchers a clearer understanding of the early emergence of Alzheimer’s disease risk factors and their association with cognition before middle age.
According to Aiello, the results reveal that several well-established risk factors and blood biomarkers are linked to cognitive function even before midlife. These earlier life associations, provide a baseline for predicting long term trajectories of cognitive decline.
“Additionally, we learned that certain Alzheimer’s risk factors—such as cardiovascular health, ATN (amyloid, tau, neurodegeneration), and immune biomarkers—are present and related to cognition in individuals in their forties and even earlier.”
Study Design and Methods
Aiello and colleagues used the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score, which covers factors like age, education, sex, systolic blood pressure, body mass index, cholesterol, physical activity, and the gene variant apolipoprotein E ε4 allele (APOE ε4) which is a genetic risk factor for Alzheimer’s disease.
Data were analyzed from Waves IV and V of the National Longitudinal Study of Adolescent to Adult Health (Add Health), which tracked a nationally representative cohort of adolescents since 1994-1995 through multiple follow-up waves. About half of the participants in Wave IV were female (48.4–52.1%), and just over 70 percent (71.4–72.5%) were White.
In particular, Wave IV consisted of data from up to 11, 449 individuals aged 24-34. The researchers conducted in-home interviews, cognitive tests, physical exams, and gathered blood samples from 4,507 participants. In Wave V, both in-person and web/mail surveys were directed to participants aged 34-44.
The total of 1,112 participants who received in-home interviews, were given cognitive tasks such as immediate word recall, delayed word recall, and backward digit span and provided a sample for genetic testing. Scores on the cognitive tasks were linked to the overall CAIDE score in 529 individuals at Wave V.
Early Biomarker and Genetic Insights
“Exploring the relationship between the CAIDE score and cognitive function in young adulthood and early midlife in the U.S., showed that significant associations with cardiovascular risk factors can be observed well before age 50,” Aiello explained.
Furthermore, biologically — genetic, neurological, immune, and inflammatory biomarkers have been implicated in Alzheimer’s disease risk. The amyloid (A), tau (T), and neurodegeneration (N) biomarkers—collectively known as ATN—are increasingly viewed as promising indicators for predicting Alzheimer’s disease risk in older populations. ATN biomarker and several immune markers showed associations with cognitive function before midlife. However, a key genetic risk factor, APOE, did not appear to affect participants in these middle years and may not become evident until later in life.
“Our overall findings suggest that blood-based biomarkers associated with Alzheimer’s disease are linked to differences in cognitive function decades before clinical symptoms and impairments even appear, highlighting the importance of early prevention strategies across the life course,” Aiello noted. “Identifying the early pathways to Alzheimer’s disease and cognitive impairment before older age is critical to slowing the expected rise of Alzheimer’s disease in the coming decades.”
Reference: “Risk factors for Alzheimer’s disease and cognitive function before middle age in a U.S. representative population-based study” by Allison E. Aiello, Jennifer Momkus, Rebecca C. Stebbins, Yuan S. Zhang, Chantel L. Martin, Y. Claire Yang, Lauren Gaydosh, Taylor Hargrove, Adina Zeki Al Hazzouri and Kathleen Mullan Harris, 5 April 2025, The Lancet Regional Health – Americas.
DOI: 10.1016/j.lana.2025.101087
Co-authors are Jennifer Momkus, Chantel L. Martin, Lauren Gaydosh, Y. Claire Yang, Taylor Hargrove, and Kathleen Mullan Harris, University of North Carolina at Chapel Hill; Rebecca C. Stebbins, Butler Columbia Aging Center; Yuan S. Zhang and Adina Zeki Al Hazzouri, Butler Columbia Aging Center and Mailman School of Public Health.
The study was supported by Add Health, grant P01HD31921 , the Eunice Kennedy Shriver National Institute of Child Health and Human Development , P2CHD050924, cooperative funding from 23 other federal agencies and foundations, the National Institute on Aging, grants U01AG071448 and U01AG071450; and R01AG057800 & P30AG066615 from NIA and T32HD091058.
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