High-density lipoprotein cholesterol is associated with lowered cognitive recovery among acute ischemic stroke patients with mild cognitive impairment

High-density lipoprotein (HDL) has been documented to be related to mild cognitive impairment (MCI) and dementia occurrence; however, the underlying basis behind this association remains unclear. We aimed to elucidate this basis by examining the association between HDL levels and cognitive improvements after 6 months, among acute ischemic stroke (AIS) patients with MCI. Five hundred fifty-eight AIS and MCI patients from the NICE study were enrolled, and divided into four groups, according to their baseline HDL quartiles; median HDL was 1.12 mmol/L (interquartile range 0.96-1.34 mmol/L). The primary outcome examined was the extent of cognitive improvement, defined as Delta MoCA (Montreal Cognitive Assessment) >= 2, while the secondary outcome was cognitive deterioration, defined as Delta ADAS-cog (Alzheimer's Disease Assessment Scale-Cognitive Subscale) >= 4 or Delta MMSE (Mini-Mental State Examination) <= - 3, at 6-months post-AIS. We found that 314 (56.27%), 49 (8.78%), and 31 (5.56%) patients had Delta MoCA >= 2, Delta ADAS-cog >= 4, and Delta MMSE <= - 3, respectively. Furthermore, cognitive improvement negatively correlated to HDL levels, with the lowest being present among patients in quartiles 4 (Q4; adjusted OR = 0.44, 95% CI 0.25-0.78, P = 0.0050) and Q3 (OR = 0.38, CI 0.23-0.65, P = 0.0004), compared to Q2 (OR = 0.57, CI 0.34-0.96, P = 0.0331). Q2 patients also had positive correlations with Delta ADAS-cog >= 4 (OR = 5.18, CI 1.55-17.29, P = 0.0074). However, no association between HDL and Delta MMSE <= - 3 was observed, nor with LDL and any cognitive changes. Additionally, restricted cubic spline analysis found a nonlinear relationship between HDL and cognitive improvements. All these findings suggested that low plasma HDL was positively associated with improved cognitive functioning among AIS patients with MCI after 6 months.