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

Abstract

ObjectiveTo 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.MethodsParticipants 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.ResultsThe 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 (F2,423 = 3.78, p = 0.024) and with lowered memory scores (F2,423 = 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).ConclusionReverse 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.

Nighttime Blood Pressure Interacts with APOE Genotype to Increase the Risk of Incident Dementia of the Alzheimer’s Type in Hispanics

“…Some researchers have suggested that APOE-4 predisposes carriers to cerebrovasculature damage by hypertension [39]. Both APOE-4 and altered nocturnal dipping profile have been associated with increased white matter hyperintensity volume [40,41]. Therefore, the results presented here support the notion that co-occurrence of APOE-4 and increased nighttime BP may increase the likelihood of small vessel disease, which in turn increases the likelihood of DAT development.…”

MRI‐Based Investigation of Association Between Cerebrovascular Structural Alteration and White Matter Hyperintensity Induced by High Blood Pressure

“…To further examine the relationships among cerebrovascular morphologies, high BP, and WMH, the mediation analysis was conducted with a linear single-mediator model. 22,23 The mediation models used cerebrovascular morphologies as the mediator, WMH status as the response, and treated BP as the determinant. Confounders including age, sex, body mass index, and whole brain volumes were adjusted for each mediation model.…”

Blood Pressure Profiles and Cognitive Function from Adulthood to Old Age: Chasing a Golden Middle Way?

“…Besides daytime BP profile, nighttime BP is also emerging as a relevant contributor to cardiovascular health and disease. Consistent with this, poor nocturnal BP control, expressed as reverse dipping, appears to have a relevant role in hypertension-associated small vessel cerebrovascular disease and related memory impairment [ 19 ]. A particularly detrimental effect of reverse dipping on cognitive function has been described in elderly adults [ 19 , 20 ].…”