Associations between low circulatory low-density lipoprotein cholesterol level and brain health in non-stroke non-demented subjects

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 ( p  = 0.003) and posterior cingulate (β = −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 (β = −0.073; p  = 0.021), highest periventricular WMH (β = 0.089; p  = 0.011) and lowest verbal memory test scores (β = −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.