Relationships between educational attainment, hypertension, and amyloid negative subcortical vascular dementia: The brain-battering hypothesis

Purpose: Many epidemiological studies suggest that lower education levels and vascular risk factors increase the likelihood of developing Alzheimer's disease dementia (ADD) and subcortical vascular dementia (SVaD). However, whether the brain-battering hypothesis can explain the relationship between education levels and the clinical diagnosis of dementia remains controversial. The objective of this study was to investigate whether vascular risk factors mediate the association between education level and the diagnosis of amyloid-beta positive (Aβ+) ADD and amyloid-beta negative (Aβ-) SVaD. Methods: We analyzed 376 participants with Aβ normal cognition (Aβ- NC), 481 with Aβ+ ADD, and 102 with Aβ- SVaD. To investigate the association of education level and vascular risk factors with these diagnoses, multivariable logistic regression analysis was used, with age, sex, and APOE ε4 carrier status used as covariates. Path analysis was performed to investigate the mediation effects of hypertension on the diagnosis of Aβ- SVaD. Results: The Aβ- SVaD group (7.9 ± 5.1 years) had lower education levels than did the Aβ- NC (11.8 ± 4.8 years) and Aβ+ ADD (11.2 ± 4.9 years) groups. The frequencies of hypertension and diabetes mellitus were higher in the Aβ- SVaD group (78.4 and 32.4%, respectively) than in the Aβ- NC (44.4 and 20.8%) and Aβ+ ADD (41.8 and 15.8%, respectively) groups. Increased education level was associated with a lower risk of Aβ- SVaD [odds ratio (OR) 0.866, 95% confidence interval (CI), 0.824–0.911], but not Aβ+ ADD (OR 0.971, 95% CI 0.940–1.003). The frequency of hypertension was associated with a higher risk of developing Aβ- SVaD (OR 3.373, 95% CI, 1.908–5.961), but not Aβ+ ADD (OR 0.884, 95% CI, 0.653–1.196). In the path analysis, the presence of hypertension partially mediated the association between education level and the diagnosis of Aβ- SVaD. Conclusion: Our findings revealed that education level might influence the development of Aβ- SVaD through the brain-battering hypothesis. Furthermore, our findings suggest that suitable strategies, such as educational attainment and prevention of hypertension, are needed for the prevention of Aβ- SVaD.