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Mediating Role of White Matter Hyperintensities in the Association Between Hypertension and Cognitive Impairment: A Population-Based Prospective Cohort Study
Background: Hypertension is a well-established risk factor for cognitive decline; however, its underlying mechanisms remain unclear. White matter hyperintensities, a marker of cerebral small vessel disease, may mediate the association between vascular risk and cognitive impairment. We examined the longitudinal relationships among hypertension, white matter hyperintensity burden, and cognitive performance.
Methods: Data were obtained from the Korean Genome Epidemiology Study-Ansan Aging Study, a population-based prospective cohort. Hypertension was defined at baseline. White matter hyperintensity volume was quantified using brain structural MRI at the 4-year follow-up, and cognitive performance was assessed at the 8-year follow-up. Multivariable linear regression and mediation analyses were conducted to evaluate associations and quantify indirect effects.
Findings: Among 2,087 participants, baseline hypertension was associated with greater white matter hyperintensity burden (β = 0.646 mL, p <0.001) and poorer cognitive performance at follow-up. The largest deficits were observed in processing speed and working memory including the Digit Symbol Coding test (β = -1.251, p = 0.04) and the Trail Making test Part A (β = 2.627, p = 0.001). White matter hyperintensity burden partially mediated this association, accounting for 13.8% of the total effect in the Digit Symbol Coding test.
Interpretation: Hypertension may contribute to cognitive decline through vascular-related brain changes reflected by increased white matter hyperintensity burden. These findings support the mediating role of white matter hyperintensities in linking hypertension to cognitive impairment and emphasize the importance of blood pressure control for brain health.
Nam, Hye Ryeong and Choi, Jisun and Siddiquee, Ali T. and Lee, Jisoo and Kim, Hyun and Kim, Regina EY and Lee, Seung Ku and Kim, Nan Hee and Kim, Soriul and Shin, Chol, Mediating Role of White Matter Hyperintensities in the Association Between Hypertension and Cognitive Impairment: A Population-Based Prospective Cohort Study. Available at SSRN: https://ssrn.com/abstract=6861475
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