Association of estimated white matter hyperintensity age with cognition in elderly with controlled hypertension

Introduction: Hypertension is associated with white matter hyperintensity (WMH) and cognitive impairment. Further, WMH is associated with cognitive impairment including executive, attention and visuospatial functions. The aim of this study was to investigate the effects of controlled hypertension (cHT) and previously developed concept, 'WMH age' on cognitive function and the mediating role of WMH in the effect of cHT on cognitive impairment.Methods: We enrolled 855 Koreans without dementia aged 60 years or older, 326 of whom completed 2-year follow-up assessment. We measured their blood pressure thrice in a sitting position using an automated blood pressure monitoring device. We estimated 'WMH age' of every participant using previously developed WMH probability map of healthy older Koreans. We analyzed the mediating effect of WMH age in the association of cHT and cognitive function using the PROCESS Macro model.Results: Old WMH age was associated with a faster decline in the Mini-Mental Status Examination (MMSE; p =.003), Consortium to Establish a Registry for Alzheimer's Disease total score (CERAD-TS; p =.003), and Frontal Assessment Battery (FAB; p =.007). Old WMH age showed an approximately-six times higher risk of incident mild cognitive impairment (OR = 6.47, 95 % CI = 1.37 - 9.50, p =.024) compared to young or normal WMH age over the 2-year follow-up period in the cHT group. WMH age mediated the effects of cHT on the MMSE, CERADTS, and FAB scores at baseline and two-year follow-up period.Conclusions: WMH mediates the adverse effect of hypertension on cognitive function. Elders with cHT who have older WMH age may be at a higher risk of cognitive decline.