The Role of Inflammation and Psycho-Behavioral Factors as Mediators Between Acculturation and Time to Incident Dementia Among Older Mexican Americans

Article type: Research Article

Authors: Nianogo, Roch A.^{a; b; *} | Hays, Ron D.^c | Gong, Yufan^a | Yu, Yu^a | Ritz, Beate^{a; d; e} | Duru, O. Kenrik^c

Affiliations: [a] Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA | [b] California Center for Population Research, University of California, Los Angeles, Los Angeles, CA, USA | [c] Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA | [d] Department of Environmental Health Sciences, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA | [e] Department of Neurology, UCLA David Geffen School of Medicine, Los Angeles, CA, USA

Correspondence: [*] Correspondence to: Roch A. Nianogo, MD, PhD, Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA. E-mail: niaroch@ucla.edu.

Abstract: Background:The mechanisms through which acculturation influences the onset of cognitive impairment and dementia are not well understood, especially among older Hispanics. Objective:To investigate whether inflammation and psycho-behavioral factors mediate the relationship between acculturation and incident dementia among older Mexican Americans. Methods:We analyzed the Sacramento Area Latino Study on Aging (1998–2007, SALSA), a longitudinal study (N = 1,194) with 10 years of follow-up, and used g-computation for mediation analysis with pooled logistic regression to evaluate whether acculturation (assessed by the Revised Acculturation Rating Scale for Mexican Americans [ARSMA-II]) affected dementia or cognitive impairment but not dementia (CIND) through inflammation (i.e., interleukin 6 [IL-6], tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein [hs-CRP]), smoking, alcohol consumption, and depressive symptoms. The potential mediators were assessed at baseline. Results:The 10-year average adjusted risk ratio (aRR) for the effect of high U.S. acculturation and dementia/CIND was 0.66, 95% CI (0.36, 1.30). The indirect effects were: IL-6 (aRR = 0.98, 95% CI (0.88, 1.05)); TNF-α (aRR:0.99, 95% CI (0.93, 1.05)); hs-CRP: (aRR = 1.21, 95% CI (0.84, 1.95)); current smoking: aRR = 0.97, 95% CI (0.84, 1.16); daily/weekly alcohol consumption (aRR = 1.00, 95% CI (0.96, 1.05)); and depressive symptom score (aRR = 1.03, 95% CI (0.95, 1.26)). Hs-CRP yielded a proportion mediated of -26%, suggesting that hs-CRP could suppress the potential effect of high U.S. acculturation. The other factors explored resulted in little to no mediation. Conclusions:The effect of acculturation on time to incident dementia/CIND varied over time. Our study suggests that inflammation could suppress the effect between high U.S. acculturation and dementia risk.

Keywords: Acculturation, Alzheimer’s disease, causal inference, dementia, disparities, inflammation, mediation, Mexican, stress

DOI: 10.3233/JAD-231341

Journal: Journal of Alzheimer's Disease, vol. 101, no. 2, pp. 463-473, 2024