Pathways explaining racial/ethnic disparities in incident all-cause and Alzheimer's disease dementia among older US men and women

Abstract

Introduction: Racial disparities in Alzheimer's disease (AD) and all-cause dementia (DEMENTIA) incidence may exist differentially among men and women, with unknown mechanisms.

Methods: A retrospective cohort study examining all-cause and AD dementia incidence was conducted linking Third National Health and Nutrition Examination Survey (NHANES III) to Centers for Medicare & Medicaid Services Medicare data over ≤26 years of follow-up (1988 to 2014). Cox regression and generalized structural equation models (GSEMs) were constructed among men and women ≥60 years of age at baseline (N = 4592). Outcomes included onset ages of all-cause and AD dementia, whereas the main exposures were race/ethnicity contrasts (RACE_ETHN). Potential mediators) included socio-economic status (SES), lifestyle factors (dietary quality [DIET] nutritional biomarkers [NUTR], physical activity [PA], social support [SS], alcohol [ALCOHOL], poor health [or HEALTH], poor cognitive performance [or COGN]. In addition to RACE_ETHN, the following were exogenous covariates in the GSEM and potential confounders in Cox models: age, sex, urban-rural, household size, and marital status.

Results: Non-Hispanic Black (NHB) women had a higher risk of DEMENTIA versus non-Hispanic White (NHW) women in GSEM, consistent with Cox models (age-adjusted model: hazard ratio [HR] = 1.34, 95% confidence interval [CI]: 1.10 to 1.61). The total effect of this RACE_ETHN contrast in women was explained by four main pathways: (1) RACE_ETHN→ poor cognitive performance (COGN, +) → DEMENTIA (+); (2) RACE_ETHN → SES (-) → COGN (-) → DEMENTIA (+); (3) RACE_ETHN → SES (-) → physical activity (PA, +) → COGN (-) → DEMENTIA (+); and (4) RACE_ETHN → SES (-) → DIET (+) → COGN (-) → DEMENTIA (+). A reduced AD risk in Mexican American (MA) women versus NHW women upon adjustment for SES and downstream factors (HR = 0.53, 95% CI: 0.35 to 0.80). For the non-White versus NHW contrast in incident DEMENTIA, pathways involved lower SES, directly increasing cognitive deficits (or indirectly through lifestyle factors), which then directly increases DEMENTIA .

Discussion: Socioeconomic and lifestyle factors explaining disparities between NHB and NHW in dementia onset among women are important to consider for future observational and intervention studies.

Keywords: Alzheimer's disease; aging; dementia; modifiable risk factors; racial disparities; structural equations modeling.

FIGURE 1

Full generalized structural equation model (GSEM) and hypothesized pathway. AD = Alzheimer's disease; ALCOHOL = alcohol consumption, z‐score; COGN = cognitive performance principal component variable (four measured variables); DIET/NUTR = diet and nutritional biomarkers z‐score variable (two dietary quality measures and four nutritional biomarkers); HEALTH = health‐related factors as mean of z‐scores for allostatic load, self‐rated health, co‐morbidity index and body mass index; LIFESTYLE = lifestyle‐related factors composed of social support, physical activity, diet/nutritional biomarkers, smoking, and alcohol consumption using means of z‐scores for related measured variables; MA = Mexican American; NHANES III = Third National Health and Nutrition Examination Survey; NHB = non‐Hispanic Black; NHW = non‐Hispanic White; PA = physical activity z‐score variable (three measured variables); RACE_ETHN = racial/ethnic contrast; SES = socio‐economic status mean of z‐scores composed of poverty income ratio and education (years); SMOKING = smoking z‐score variable (two measured variables); SS = social support z‐score variable (five measured variables). See Methods section for more details. Notes: Plain arrows are statistically significant associations (P < 0.05) within the hypothesized pathway; dashed arrows are statistically significant associations (P < 0.05) outside the hypothesized pathway

FIGURE 2

Generalized structural equation model (GSEM) findings for three race/ethnicity contrasts among men and women, NHANES III (1988‐1994): Final eligible sample (N = 4592). AD = Alzheimer's Disease; ALCOHOL = alcohol consumption, z‐score; COGN = Cognitive performance principal component variable (four measured variables); DIET/NUTR = diet and nutritional biomarkers z‐score variable (two dietary quality measures and four nutritional biomarkers); HEALTH = health‐related factors as mean of z‐scores for allostatic load, self‐rated health, co‐morbidity index and body mass index; LIFESTYLE = lifestyle‐related factors composed of social support, physical activity, diet/nutritional biomarkers, smoking and alcohol consumption using means of z‐scores for related measured variables; MA = Mexican American; N = Number of participants; NHANES III = Third National Health and Nutrition Examination Survey; NHB = non‐Hispanic Black; NHW = non‐Hispanic White; PA = physical activity z‐score variable (three measured variables); RACE_ETHN = racial/ethnic contrast; SES = socio‐economic status mean of z‐scores composed of poverty income ratio and education (years); SMOKING = smoking z‐score variable (two measured variables); SS = social support z‐score variable (five measured variables); TE = total effect; See Methods section for more details. Notes: Plain arrows are statistically significant associations (P < .05) within the hypothesized pathway; dashed arrows are statistically significant associations (P < .05) outside the hypothesized pathway; red arrows indicate positive (+) associations; blue arrows indicate inverse (−) associations

FIGURE 3

Generalized structural equation model (GSEM) findings for non‐White versus NHW racial/ethnic contrast versus DEMENTIA, NHANES III (1988‐1994): Final eligible sample (N = 4592). ALCOHOL = alcohol consumption, z‐score; COGN = cognitive performance principal component variable (four measured variables); DIET/NUTR = diet and nutritional biomarkers z‐score variable (two dietary quality measures and four nutritional biomarkers); HEALTH = health‐related factors as mean of z‐scores for allostatic load, self‐rated health, co‐morbidity index, and body mass index; LIFESTYLE = lifestyle‐related factors composed of social support, physical activity, diet/nutritional biomarkers, smoking, and alcohol consumption using means of z‐scores for related measured variables; MA = Mexican American; N = number of participants; N' = number of observations; NHANES III = Third National Health and Nutrition Examination Survey; NHB = non‐Hispanic Black; NHW = non‐Hispanic White; PA = physical activity z‐score variable (three measured variables); RACE_ETHN = racial/ethnic contrast; SES = socio‐economic status mean of z‐scores composed of poverty income ratio and education (years); SMOKING = smoking z‐score variable (two measured variables); SS = social support z‐score variable (five measured variables); TE = total effect; see Methods section for more details. Notes: Plain arrows are statistically significant associations (P < 0.05) within the hypothesized pathway; dashed arrows are statistically significant associations (P < 0.05) outside the hypothesized pathway; red arrows indicate positive (+) associations; blue arrows indicate inverse (−) associations