White matter hyperintensities mediate the association of nocturnal blood pressure with cognition

Abstract

Objective: To test the hypotheses that hypertension and nocturnal blood pressure are related to white matter hyperintensity (WMH) volume, an MRI marker of small vessel cerebrovascular disease, and that WMH burden statistically mediates the association of hypertension and dipping status with memory functioning, we examined the relationship of hypertension and dipping status on WMH volume and neuropsychological test scores in middle-aged and older adults.

Methods: Participants from the community-based Maracaibo Aging Study received ambulatory 24-hour blood pressure monitoring, structural MRI, and neuropsychological assessment. Four hundred thirty-five participants (mean ± SD age 59 ± 13 years, 71% women) with available ambulatory blood pressure, MRI, and neuropsychological data were included in the analyses. Ambulatory blood pressure was used to define hypertension and dipping status (i.e., dipper, nondipper, and reverse dipper based on night/day blood pressure ratio <0.9, 0.9-1, and >1, respectively). Outcome measures included regional WMH and memory functioning derived from a neuropsychological test battery.

Results: The majority of the participants (59%) were hypertensive. Ten percent were reverse dippers, and 40% were nondippers. Reverse dipping in the presence of hypertension was associated with particularly elevated periventricular WMH volume (F _2,423 = 3.78, p = 0.024) and with lowered memory scores (F _2,423 = 3.911, p = 0.021). Periventricular WMH volume mediated the effect of dipping status and hypertension on memory (β = -4.1, 95% confidence interval -8.7 to -0.2, p < 0.05).

Conclusion: Reverse dipping in the presence of hypertension is associated with small vessel cerebrovascular disease, which, in turn, mediates memory functioning. These results point toward reverse dipping as a marker of poor nocturnal blood pressure control, particularly among hypertensive individuals, with potentially pernicious effects on cerebrovascular health and associated cognitive function.

Figure 1. WMH volume as a function of hypertension and dipping status

In each graph, the central bar represents the median, box marks the first and third quartiles, and bars extend 1.5 times the width of the box. Remaining points represent values outside this range. The y-axes are logarithmically scaled. (A) Reverse dipping in the presence of hypertension is associated with higher accumulation of periventricular white matter hyperintensity (WMH) volume at almost twice the rate of any other group. (B) There is no observed association among dipping status, hypertension, and deep WMH volume.

Figure 2. Total learning score as a function of hypertension and dipping status

Reverse dipping in the presence of hypertension is associated with markedly lower memory function compared with all other groups. The central bar represents the median; box marks the first and third quartiles; and bars extend 1.5 times the width of the box. Remaining points represent values outside this range.