Association of education attainment, smoking status, and alcohol use disorder with dementia risk in older adults: a longitudinal observational study

Abstract

Background: Previous research on the risk of dementia associated with education attainment, smoking status, and alcohol use disorder (AUD) has yielded inconsistent results, indicating potential heterogeneous treatment effects (HTEs) of these factors on dementia risk. Thus, this study aimed to identify the important variables that may contribute to HTEs of these factors in older adults.

Methods: Using 2005-2021 data from the National Alzheimer's Coordinating Center (NACC), we included older adults (≥ 65 years) with normal cognition at the first visit. The exposure of interest included college education or above, current smoking, and AUD and the outcome was all-cause dementia. We applied doubly robust learning to estimate risk differences (RD) and 95% confidence intervals (CI) between exposed and unexposed groups in the overall cohort and subgroups identified through a decision tree model.

Results: Of 10,062 participants included, 929 developed all-cause dementia over a median 4.4-year follow-up. College education or above was associated with a lower risk of all-cause dementia in the overall population (RD, -1.5%; 95%CI, -2.8 to -0.3), especially among the subpopulations without hypertension, regardless of the APOE4 status. Current smoking was not related to increased dementia risk overall (2.8%; -1.5 to 7.2) but was significantly associated with increased dementia risk among men with (21.1%, 3.1 to 39.1) and without (8.4%, 0.9 to 15.8) cerebrovascular disease. AUD was not related to increased dementia risk overall (2.0%; -7.7 to 11.7) but was significantly associated with increased dementia risk among men with neuropsychiatric disorders (31.5%; 7.4 to 55.7).

Conclusions: Our studies identified important factors contributing to HTEs of education, smoking, and AUD on risk of all-cause dementia, suggesting an individualized approach is needed to address dementia disparities.

Keywords: Alcohol use disorder; All-cause dementia; College education; Smoking; Social and behavioral determinants of health.

Fig. 1

Flowchart of participant selection. NACC, National Alzheimer’s Coordinating Center; FDA, Food and Drug Administration

Fig. 2

Heterogeneous treatment effects of education attainment (A), smoking status (B), and alcohol use disorder (C) on risk of all-cause dementia. The predicted individualized treatment effect (ITE) was presented as an absolute risk difference in risk of dementia between exposure and non-exposure for each participant (Y-axis). The predicted ITE is divided into 10 groups according to the deciles (X-axis). Different colors represent participants in distinct subgroups identified by the single decision tree model

Fig. 3

Absolute risk difference in risk of all-cause dementia associated with education attainment (A), smoking status (B), and alcohol use disorder (C) in the overall population and subgroups identified by the single decision tree model. CI, confidence interval