LAUSR

ABSTRACT Low‐density lipoprotein cholesterol (LDL‐C) and hypertension have independent and synergistic effects on atherosclerotic cardiovascular disease. However, the role of circulatory LDL‐C and its possible interactions with hypertension in brain health have been poorly investigated. The study aimed to investigate the relationship between the circulatory LDL‐C level and (1) brain structures, grey‐matter volume (GMV) and white matter hyperintensity (WMH) and (2) cognitive functions, and whether hypertension plays a role in these relationships. Subjects who were non‐stroke and non‐demented were prospectively recruited from the community‐based I‐Lan Longitudinal Aging Study. High‐resolution 3T MRI was performed with GM and WMH segmentation. GMVs, total and regional including Alzheimer's disease‐susceptible area, and WMH volumes were measured. Neurological tests including verbal memory, visuospatial, and verbal executive functions were assessed. Eight‐hundred‐and‐two participants (59.2±5.7 years; 44% men) were included. Multivariate linear regression analyses showed that low circulatory LDL‐C levels (<98mg/dL) were significantly associated with reduced GMVs in frontal (standardized &bgr;=−0.130; p=0.003) and posterior cingulate (&bgr;=−0.113; p=0.032) regions in hypertensive but not normotensive subjects. In addition, low circulatory LDL‐C levels, combined with hypertension, had the lowest posterior cingulate GMV (&bgr;=−0.073; p=0.021), highest periventricular WMH (&bgr;=0.089; p=0.011) and lowest verbal memory test scores (&bgr;=−0.088; p=0.035) compared with neither low circulatory LDL‐C level nor hypertension, and either hypertension or low circulatory LDL‐C level. Age, sex, total intracranial volume, vascular risk factors, level of other circulatory lipids, and the taking of anti‐hypertensive and lipid‐lowering medications were adjusted. In conclusion, the role of circulatory LDL‐C level and its interactive effect with hypertension on brain health are firstly demonstrated. A low circulatory LDL‐C level was associated with reduced regional brain GMVs in hypertensive but not normotensive subjects. In addition, there seems a combined detrimental‐effect of low circulatory LDL‐C levels with hypertension on posterior cingulate GMV, WMH, and verbal memory. HIGHLIGHTSReduced regional grey‐matter volumes in subjects with low level of circulatory LDL cholesterol (LDL‐C).Combined effects of low circulatory LDL‐C with hypertension (HTN) on brain structures and functions.Reduced posterior cingulate grey‐matter volume in low circulatory LDL‐C combined with HTN.Combined effects also include higher white matter hyperintensities and poorer memory.