Immune function, cortisol, and cognitive decline & dementia in an aging latino population. (November 2021) - Stebbins, Rebecca C.
Abstract: Background: The etiology of dementias and cognitive decline remain largely unknown. It is widely accepted that inflammation in the central nervous system plays a critical role in the pathogenesis of dementia. However, less is known about the role of the peripheral immune system and interactions with cortisol, though evidence suggests that these, too, may play a role. Methods: Using data from 1337 participants aged 60+ years from the Sacramento Area Latino Study of Aging (observational cohort) we investigated variation in trajectories of cognitive decline by pathogen IgG and cytokine levels. Linear mixed effects models were used to examine the association between baseline Interleukin (IL)−6, C-reactive protein, tumor necrosis factor (TNF)- α, and five persistent pathogens' IgG response and trajectories of cognition over 10 years, and to examine interactions between immune biomarkers and cortisol. Stratified cumulative incidence functions were used to assess the relation between biomarkers and incident dementia. Inverse probability weights accounted for loss-to-follow-up and confounding. Results: IL-6, TNF- α, and CMV IgG were statistically significantly associated with a higher log of Modified Mini-Mental State Examination errors (IL-6, β = 0.0935 (95%CI: 0.055, 0.13), TNF-alpha β = 0.0944 (95%CI: 0.032, 0.157), and CMV, β = 0.0409 (95%CI: 0.013, 0.069)). Furthermore, cortisol interacted with HSV-1 and IL-6, and CRP for both cross-sectional cognitive function and rate of decline. No statistically significant relationship was detected between biomarkers and incidence of dementia. Conclusions: These findings support the theory that the peripheral immune system may play a role in cognitive decline but not incident dementia. Furthermore, they identify specific markers amenable for intervention for slowing decline. Highlights: Investigated immune biomarkers & cognition in a 10-year longitudinal study of older Latinos in Sacramento County, CA. Higher IL-6, TNF- α, and CMV IgG associated with lower cognition, using IP weights for confounding and informative censoring. Cortisol interacted with HSV-1, IL-6, and CRP for cross-sectional cognitive function or rate of decline. No statistically significant relationship was detected between biomarkers and incidence of dementia.