Alzheimer's risk factors linked to cognition as early as young adulthood

A new study from Columbia University Mailman School of Public Health and the Columbia Butler Aging Center suggests that risk factors and biomarkers related to Alzheimer's disease are associated with cognition much earlier in life than previously recognized. The study highlights significant associations between cognition and Alzheimer's disease risk factors as young as ages 24 to 44 and underscores the importance of early prevention. This is the first study to systematically examine Alzheimer's disease risk factors, including biomarkers related to cognitive impairment in a large group of generally healthy middle-aged individuals in the U.S. 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."

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.

"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. 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."

Allison Aiello, PhD, James S. Jackson Healthy Longevity Professor of Epidemiology in the Butler Aging Center and Columbia Mailman School

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.