U-shaped Association Between Post-stroke Cognitive Impairment and High-density Lipoprotein Cholesterol at the Acute Period of Stroke

 How are you measuring brain cholesterol? You explain nothing on why body cholesterol impacts the brain. Useless, and your mentors and senior researchers signed off on this crapola?

The human brain, though only 2% of body weight, holds about 20-25% of the body's total cholesterol, which is mostly synthesized within the brain itself due to the blood-brain barrier (BBB). Brain cholesterol is essential for maintaining cell membranes, myelin sheaths, and synaptic function, with myelin containing the majority of it. This internal production and the presence of the BBB separate brain cholesterol metabolism from peripheral levels, requiring separate, independent regulation

U-shaped Association Between Post-stroke Cognitive Impairment and High-density Lipoprotein Cholesterol at the Acute Period of Stroke

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https://doi.org/10.1016/j.archger.2025.106002Get rights and content

Highlights

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  The study reveals a U-shaped curvilinear relationship between acute-phase HDL-C levels and both cognitive status (at baseline and 3 months) and brain structure in stroke patients, indicating that extreme HDL-C levels (high or low) correlate with poorer outcomes.
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  Contrary to conventional assumptions, excessively high HDL-C in stroke patients does not confer cognitive protection, aligning with prior evidence
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  Even within the European guideline's "normal" HDL-C range, acute-phase levels that are too high or low negatively impact post-stroke cognition, suggesting narrower optimal thresholds

Abstract

Post-stroke cognitive impairment (PSCI) imposes a significant economic and social burden on patients and their families. High-density lipoprotein cholesterol (HDL-C) is reported to have protective effects on cognitive function in older adults. This study assesses the effects of HDL-C during the acute period of stroke on PSCI. This sub-study of the China National Clinical Research Center Alzheimer's Disease and Neurodegenerative Disorder Research (CANDOR) prospectively enrolled patients with acute ischemic stroke. HDL-C levels and brain magnetic resonance imaging findings were examined at the acute stage. All participants completed neuropsychological assessment at the 3 months. 394 acute ischemic patients were enrolled, 297 (75.4%) were man, mean age was 58.14±9.25 years, and all finished the baseline and 3-month cognitive assessments. HDL-C levels showed nonlinear relationships with post-stroke cognitive functions and brain structures. Participants were divided into five groups based on HDL-C levels: first-20th, 21st-40th, 41st-60th, 61st-80th, and 81st-last percentiles. The HDL-C middle group (1.03-1.15 mmol/L) had greater baseline global brain volume and regional brain volumes, the lowest incidence of PSCI at 3 months (50.0%), and better MMSE and MoCA scores in baseline and 3-month follow-up, multi-domain Z scores (construction, executive function, language and memory) in 3-month follow-up. Curve estimation further confirm the quadratic models (U-shaped curve) fit HDL-C with baseline global and regional brain volume, and cognitive performance at 3-month visits. U-shaped associations of HDL-C with post stroke cognitive function and baseline brain structures were identified. Either too high or too low HDL-C indicates a higher risk of poor post-stroke cognition.

Trail registration number

NCT04320368.