Inflammatory mechanisms underlying the effects of everyday discrimination on age-related memory decline
Introduction
Social stressors have been linked to worse episodic memory functioning. For example, self-reported everyday experiences of discrimination are associated with lower episodic memory level (Barnes et al., 2012) and faster episodic memory decline (Zahodne et al., 2017). Discrimination may be particularly relevant for memory because identity-relevant stressors can be more psychologically damaging than stressors that threaten less valued role involvements (Thoits, 1991). Indeed, elevated levels of discrimination independently mediate racial inequalities in memory aging, such that Black older adults report more discrimination than non-Hispanic Whites, and greater discrimination predicts faster subsequent memory decline (Zahodne et al., 2017). While the effects of discrimination on mental and physical health outcomes are increasingly being recognized, the biological mechanisms linking everyday discrimination to worse memory functioning are unclear. A better understanding of these mechanisms can facilitate the development and evaluation of interventions to reduce inequalities in late-life memory decline.
According to the biopsychosocial model described by Clark et al. (1999), discrimination triggers psychological and physiological stress responses that can lead to negative health outcomes. A growing body of work implicates inflammatory processes in the harmful physiological effects of everyday discrimination. Social stressors such as interpersonal discrimination likely trigger the same, highly conserved biological response as physical threat or injury (Stawski et al., 2013). Chronic stress-related activation of the sympathetic nervous system (i.e., norepinephrine release), and the hypothalamic–pituitary–adrenal axis (i.e., glucocorticoid resistance) both up-regulate the transcription of pro-inflammatory cytokines (Slavich and Irwin, 2014), including interleukin-6 (IL-6). Epidemiological studies have documented positive associations between self-reported discrimination and levels of IL-6 (Kershaw et al., 2016), as well as C-reactive protein (CRP) (Beatty Moody et al., 2014, Lewis et al., 2010), an acute-phase protein secreted in response to elevated levels of pro-inflammatory cytokines. Inflammation induces immune cells to migrate into vascular lesions, leading to adiposity, plaque instability, and thrombi formation, which occludes arteries and triggers clinical and subclinical coronary events (Ross, 1999, Tracy, 1998, Wick et al., 1995). Thus, inflammatory mechanisms likely underlie associations between everyday discrimination and many important health outcomes, including incident cardiovascular disease (Everson-Rose et al., 2015) and mortality (Barnes et al., 2008).
In addition to these important health outcomes, inflammation may also underlie associations between everyday discrimination and age-related memory decline. Indeed, elevated levels of CRP have been associated with worse performance on episodic memory tasks (Bettcher et al., 2012, Marsland et al., 2015), and an experimental animal study demonstrated that administering CRP to rats led to impaired long-term memory (Lin et al., 2009). Peripheral inflammation can modulate central inflammatory processes, resulting in neurodegeneration (Heyser et al., 1997). Indeed, correlational evidence suggests that brain volumes, particularly within the temporal lobe, mediate associations between peripheral inflammation and episodic memory performance (Bettcher et al., 2012, Marsland et al., 2015). Episodic memory may be particularly susceptible to the negative effects of inflammation due to relatively high concentrations of pro-inflammatory cytokines and their receptors in brain regions important for memory, including the hippocampus (Schöbitz et al., 1994). Together, the studies reviewed provide rationale for the hypothesis that inflammatory processes mediate the effects of everyday discrimination on episodic memory.
Embedded within the biopsychosocial framework (Clark et al., 1999), the overall goal of the current study was to provide empirical evidence for a social–biological pathway leading from everyday discrimination to worse episodic memory. Specifically, we aimed to determine whether systemic inflammation, indexed by blood levels of CRP, mediates associations between everyday discrimination and episodic memory over 6 years, using longitudinal cognitive and biomarker data from a nationally-representative sample of participants aged 51 and older in the Health and Retirement Study.
Section snippets
Participants
Data were drawn from the Health and Retirement Study (HRS), a nationally representative sample of Americans aged 51 and older followed since 1992 (Sonnega and Weir, 2014). Details of the HRS longitudinal panel design, sampling, and all assessment instruments are available on the HRS website (http://hrsonline.isr.umich.edu). Participants in HRS are interviewed every 2 years. In 2006, the HRS initiated an enhanced face-to-face interview, which included collecting biomarker and psychosocial data.
Results
Table 2 displays differences in the primary study variables across the different sociodemographic groups represented in this heterogeneous sample. Non-Hispanic White and Hispanic participants reported less discrimination than non-Hispanic Blacks and non-Hispanic participants who self-identified as a member of any other racial group. Non-Hispanic Blacks were most likely to have high CRP, followed by Hispanics, non-Hispanic Whites, and others. Non-Hispanic Whites obtained higher episodic memory
Discussion
This nationally representative, longitudinal study provides preliminary evidence that inflammation partially mediates the deleterious effects of everyday discrimination on episodic memory performance among older adults. While CRP significantly mediated the negative association between discrimination and episodic memory at baseline, discrimination also predicted worse memory over the 6-year study period independent of CRP and health covariates (i.e., smoking status, BMI, and chronic disease
Acknowledgments
This work was supported by the National Institute on Aging [grant numbers R00AG047963 and R01AG054520]. The HRS (Health and Retirement Study) is sponsored by the National Institute on Aging (grant number NIA U01AG009740) and is conducted by the University of Michigan. The sponsor had no role in the current analyses or the preparation of this paper.
Conflict of interest
The authors have no conflicts.
Author contributions
LBZ: conception and design, analysis and interpretation of data; drafting of the article; approval of final version. AZK: conception and design, interpretation of data; critical revisions; approval of final version. NS: interpretation of data; critical revisions; approval of final version. ABZ: interpretation of data; critical revisions; approval of final version. KS: interpretation of data; critical revisions; approval of final version.
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