Search

BackgroundThe 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.MethodsUsing 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.ResultsIL-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.ConclusionsThese 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.

Despite well-documented evidence that structurally disadvantaged populations are disproportionately affected by infectious diseases, our understanding of the pathways that connect structural disadvantage to the burden of infectious diseases is limited. We propose a conceptual framework to facilitate more rigorous examination and testing of hypothesized mechanisms through which social and environmental factors shape the burden of infectious diseases and lead to persistent inequities. Drawing upon the principles laid out by Link and Phelan in their landmark paper on social conditions (J Health Soc Behav. 1995;(spec no.):80–94), we offer an explication of potential pathways through which structural disadvantage (e.g. racism, sexism, and economic deprivation) operates to produce infectious disease inequities. Specifically, we describe how the social environment affects an individual's risk of infectious disease by 1) increasing exposure to infectious pathogens and 2) increasing susceptibility to infection. This framework will facilitate both the systematic examination of the ways in which structural disadvantage shapes the burden of infectious disease and the design of interventions that can disrupt these pathways. [ABSTRACT FROM AUTHOR]

Recent studies have documented a decline in the overall prevalence of disability in the United States; however, racial/ethnic and sex disparities continue to persist. Cytomegalovirus (CMV) infection, a socially patterned exposure, may be a key mechanism in understanding these previously documented disparities. Using data from a nationally representative study, the 2016 Health and Retirement Study, we employed Poisson log-binomial models to estimate the prevalence of disability in a comparison of CMV-seropositive and -seronegative adults and investigated effect modification by race/ethnicity and sex. Among the 9,029 participants (55% women; mean age = 67.4 years), 63% were CMV-seropositive and 15% were disabled. CMV seropositivity was highest among non-Hispanic Black (88%) and Hispanic (92%) adults as compared with non-Hispanic White adults (57%). We found evidence for effect modification in the association between CMV and disability by sex but not race/ethnicity. While the 95% confidence intervals in the fully adjusted models included the null value, in comparison with seronegative women, our results suggest a greater prevalence of disability among CMV-seropositive women (prevalence ratio = 1.16, 95% confidence interval: 0.97, 1.38) but not among men (prevalence ratio = 0.85, 95% confidence interval: 0.69, 1.06). Results provide initial support for the hypothesis that CMV may be an important determinant of sex disparities in disability. [ABSTRACT FROM AUTHOR]