Alarming findings from a study led by researchers at Columbia University’s Mailman School of Public Health and the Columbia Butler Ageing Centre suggest that risk factors and biological markers linked to Alzheimer’s disease may influence cognitive function in people as young as 24.
This is much earlier than previously thought, said the scientists, who found significant associations between cognitive performance and Alzheimer’s-related risk factors in people as young as 24 to 44-years-old, emphasising 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 Ageing Centre 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.”
Aiello said 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.”
Method
Aiello and colleagues used the Cardiovascular Risk Factors, Ageing, 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 analysed 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 more than 70% (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 like 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, agenetic insights
“Exploring the relationship between the CAIDE score and cognitive function in young adulthood and early midlife in the US showed that significant associations with cardiovascular risk factors can be observed well before 50,” Aiello added.
Furthermore, reports SciTech Daily, 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.”
Study details
Risk factors for Alzheimer’s disease and cognitive function before middle age in a US representative population-based study
Allison Aiello, Jennifer Momkus, Rebecca Stebbins, et al.
Published in The Lancet Regional Health – Americas on 5 April 2025.
Summary
Background
Alzheimer’s disease is a major health concern in the US, but most research has focused on older populations. We examined whether established risk factors and blood biomarkers are associated with cognition before midlife.
Methods
Data from the National Longitudinal Study of Adolescent to Adult Health (Add Health) were analysed. Participants were enrolled in 1994–95 (grades 7–12) and followed through 2018. We cross-sectionally analysed weighted survey and biomarker data from Waves IV and V. We measured the Cardiovascular Risk Factors, Ageing, and Incidence of Dementia (CAIDE) score comprised of age, education, sex, systolic blood pressure, body mass index, cholesterol, and physical activity and apolipoprotein E ε4 allele (APOE ε4) status. We also measured total Tau and Neurofilament light (NfL), high sensitivity C-reactive protein (hsCRP), Interleukin (IL)-1β, IL-6, IL-8, IL-10, and Tumour necrosis factor alpha (TNF-α). Outcomes included immediate word recall, delayed word recall, and backward digit span.
Findings
Analytic sample sizes ranged from 4507 to 11,449 participants in Wave IV and from 529 to 1121 participants in Wave V. The survey-weighted median (IQR) age was 28 (26–29) years in Wave IV and 38 (36–29) years in Wave V. About half of the survey-weighted Wave IV participants were female (48.4–52.1% across analytic samples), 71.4–72.5% were white, 12.5–14.9% were black, and 9.3–10.2% were Hispanic. In Wave V, 43.6–46.8% were female, 68.7–69.3% were white, 17.1%–20.0% were Black, and 7.3%–9.6% were Hispanic. The CAIDE score was associated with all cognition measures in Wave IV. For example, among adults aged 24–34, each 1-point increase in CAIDE was associated with a 0.03 standard deviation lower backward digit span score (95% CI: −0.04, −0.02). Total Tau was associated with immediate word recall in Wave V (β = −0.13, 95% CI: −0.23, −0.04). Wave IV hsCRP and IL-10 and Wave V IL-6, IL-1β, and IL-8 were also associated with lower cognitive scores.
Interpretation
Key risk factors for Alzheimer’s Disease are linked to cognitive function as early as ages 24–44, highlighting the need for early prevention in the US.
SciTech Daily article – Alzheimer’s Risk May Begin Before 30, New Study Warns (Open access)
See more from MedicalBrief archives:
New drugs a boost for Alzheimer’s treatment but finding cause must be a priority
Self-administered test predicts early signs of Alzheimer’s and dementia sooner
Driving patterns identified by GPS can pinpoint early Alzheimer’s Disease