The cross‐sectional association between peripheral TNF‐∝, white matter hyperintensities, and cognitive outcomes in the HABS‐HD study

Abstract Background Low‐grade inflammation appears with advance age, with the end result of an increase ratio of pro to anti‐inflammatory cytokines. Inflammatory cytokines are considered cerebrovascular disease markers, but the association of cytokine levels with poorer cognition is not conclusive. TNFα, a pro‐inflammatory cytokine, may have a role on neurodegenerative diseases, such as Alzheimer’s disease. The effect of peripheral TNFα on brain structure and cognitive outcomes in cognitively normal older adults is not well understood. A few studies have described this relationship in White cohorts, but there is a lack of research in minorities like Mexican Americans. Method We studied 510 cognitively normal Mexican Americans from the Health and Aging Brain Study (HABS‐HD) with signed consent, fasting blood samples, 3T MRI, clinical evaluation, and cognitive testing. TNFα was assayed via a multiple‐plex biomarker assay platform using electrochemiluminescence. White matter hyperintensities (WMH) volume was measured from FLAIR using the Statistical Parametric Mapping Lesion Segmentation Tool. Pearson correlations were used to assess the association between TNFα with WMH, global cognition (MMSE), memory (SEVLT), executive function and attention (Trails B and digit symbol substitution) measures. Linear regression was used to predict the effect of TNF‐α on WMH volume and cognitive measures. APOE4 status was assessed, and age, sex, systolic blood pressure and education were entered as covariates in the models. Result Seventy percent of the sample were female. Sample means were 62.84 years of age, 9.94 years of education, and 137.33 for systolic blood pressure (SBP). There was not significant difference in TNFα and WMH values between APOE4 carriers and non‐carriers. TNFα had a positive significant correlation with age, education, SBP, WMH volume, and digit symbol substitution scores. Linear regression showed no association between TNFα value and WMH volume nor cognitive measures, with the exception of digit symbol substitution (B = ‐2.62; t = ‐2.03; p = 0.04). Conclusion These results suggest TNFα peripheral values are not related to WMH volume, but were related to executive‐attention measures. Prospective studies are necessary to evaluate the use of TNFα as a potential biomarker of brain health in Mexican Americans.