Abstract
Background: Exploring biological variables that may serve as indicators of the development and progression of cognitive decline is currently a high-priority research area. Recent studies have demonstrated that during normal aging, individuals experience increased inflammation throughout the brain and body, which may be linked to cognitive impairment and reduced gray matter volume in the brain. Neurofilament light polypeptide (NfL), which is released into the circulation following neuronal damage, has been proposed as a biomarker for neurodegenerative diseases, and may also have utility in the context of normal aging. The present study tested associations between age, peripheral levels of the pro-inflammatory cytokine IL-6, peripheral NfL, brain volume, and cognitive performance in a sample of healthy adults over 60 years old.Methods: Of the 273 individuals who participated in this study, 173 had useable neuroimaging data, a subset of whom had useable blood data (used for quantifying IL-6 and NfL) and completed a cognitive task. Gray matter (GM) thickness values were extracted from brain areas of interest using Freesurfer. Regression models were used to test relationships between IL-6, NfL, GM, and cognitive performance. To test putative functional relationships between these variables, exploratory path analytic models were estimated, in which the relationship between age, IL-6, and working memory performance were linked via four different operationalizations of brain health: (1) a latent GM variable composed of several regions linked to cognitive impairment, (2) NfL alone, (3) NfL combined with the GM latent variable, and (4) the hippocampus alone.Results: Regression models showed that IL-6 and NfL were significantly negatively associated with GM volume and that GM was positively associated with cognitive performance. The path analytic models indicated that age and cognitive performance are linked by GM in the hippocampus as well as several other regions previously associated with cognitive impairment, but not by NfL alone. Peripheral IL-6 was not associated with age in any of the path models.Conclusions: Results suggest that among healthy older adults, there are several GM regions that link age and cognitive performance. Notably, NfL alone is not a sufficient marker of brain changes associated with aging, inflammation, and cognitive performance.
Highlights
Cognitive functioning is an essential part of everyday living, consisting of a myriad of mental processes used to learn, think, and make decisions
Age was positively correlated with IL-6 (r = 0.237, p = 0.012 n = 112), positively correlated with Neurofilament light polypeptide (NfL) (r = 0.519, p = < 0.001, n = 130) and negatively correlated with the number of correct responses on the Keep Track task (r = −0.265, p < 0.001, n = 193)
The present study explored relationships between aging, circulating IL-6 in blood samples, gray matter (GM), NfL from peripheral blood, and cognitive performance using the Keep Track Task
Summary
Cognitive functioning is an essential part of everyday living, consisting of a myriad of mental processes used to learn, think, and make decisions. Neurodegenerative diseases are associated with age such that older individuals are most at risk (Emard et al, 1995). Given the number of individuals affected by age-related cognitive decline and AD, as well as the significant negative impact of AD on daily functioning and quality of life in older adults, investigating the causes and risk factors for age-related cognitive decline and AD is an important area of research. Exploring biological variables that may serve as indicators of the development and progression of cognitive decline is currently a high-priority research area. The present study tested associations between age, peripheral levels of the pro-inflammatory cytokine IL-6, peripheral NfL, brain volume, and cognitive performance in a sample of healthy adults over 60 years old
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