This very interesting paper finds evidence of early adult impairment of cognitive function to correlate with Alzheimer's-associated biomarkers such as tau and neurofilament light chain. It is well known that Alzheimer's disease has a decades-long onset. Measurable biomarkers are associated with future pathology well in advance. Nonetheless, to extend that back to as early an age as mid-20s is a novel way of looking at the progression of cognitive decline over a lifetime. One has to wonder to what degree this is a measurement of the effects of poor lifestyle maintenance or exposure to persistent pathogens on the brain in early adult life. Similarly, whether a continuum of the same pathological processes leads unbroken from low levels in early life to high levels in late life, or whether early life and late life exhibit significantly different mechanisms that happen to converge on impaired cognitive function.
Data from the National Longitudinal Study of Adolescent to Adult Health were analyzed. Analytic sample sizes ranged from 4,507 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. We measured the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score comprised of age, education, sex, systolic blood pressure, body mass index, cholesterol, and physical activity, and also apolipoprotein E ε4 allele (APOE ε4) status. We further measured total Tau and Neurofilament light (NfL), high sensitivity C-reactive protein (hsCRP), Interleukin (IL)-1β, IL-6, IL-8, IL-10, and Tumor necrosis factor alpha (TNF-α). Outcomes included immediate word recall, delayed word recall, and backward digit span.
Several key risk factors for Alzheimer's Disease were associated with standard measures of cognition in 24- to 44-year-olds in the U.S., suggesting that these factors may be related to cognitive function decades before the onset of Alzheimer's Disease. The CAIDE score was consistently linked to all three cognitive function measures (immediate recall, delayed recall, and backward digit span). Notably, a key genetic risk factor, APOE ε4, was not associated with recall nor backward digit span, suggesting that the effects of APOE ε4 may not become apparent until middle to older age. Total Tau was associated with lower immediate word recall but not backward digit span scores. Although higher levels of NfL showed a trend toward lower backward digit span scores, the association was not statistically significant. A limited number of immune markers were significantly associated with cognitive function at ages 24-34 years; however, some of these associations appeared to become more robust in the following decade of life. For instance, IL-6 was not associated with backward digit span in Wave IV but showed a significant association with lower backward digit span in Wave V. Similarly, IL-8 was not associated with cognitive scores in Wave IV but was associated with all three measures of cognition in Wave V.
These findings suggest that cardiovascular, neurodegenerative, and immune markers may be associated with critical measures of cognitive function at much younger ages than previously recognized, with some associations becoming more prominent between the early midlife ages of 33 and 44.
Link: https://doi.org/10.1016/j.lana.2025.101087
View the full article at FightAging
