White matter microstructure disruptions mediate the adverse relationships between hypertension and multiple cognitive functions in cognitively intact older adults

Although hypertension is a prominent vascular risk factor for late-life cognitive decline, the underlying pathophysiological mechanism remains unclear. Accordingly, the aim of this study was to examine the role of white matter microstructural integrity in hypertension-related cognitive detriments. We recruited 66 cognitively normal older adults, comprising 41 hypertensive patients and 25 normotensive controls. All participants underwent a comprehensive neuropsychological battery. White matter microstructural integrity was assessed using a tract-based automatic analysis approach derived from diffusion spectrum imaging. Mediating effects of white matter integrity were evaluated using structural equation modeling analyses. The results revealed that hypertensive older adults displayed poorer processing speed, executive function, and memory encoding. Lower white matter microstructural integrity was observed in the hypertensive elderly patients, primarily in long-range association fiber bundles. In particular, low microstructural integrity in specific tract bundles connecting frontal and posterior cerebral regions was found to underlie the adverse relationships between hypertension and multiple cognitive domains, including processing speed, executive function, memory encoding, and memory retention. Our findings suggest that hypertension may impair multiple cognitive functions by undermining white matter microstructures, even in cognitively intact older adults, thus further highlighting the necessity of monitoring vascular health to prevent cognitive decline.

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