# High-density lipoprotein cholesterol and cognitive impairment: A U-shaped relationship in China’s aging population

**Authors:** Fei Wang, Xiang Shang, Qiqi Yang, Zhuang Tao, Weimin Li, Meixia Wang, Fei Li

PMC · DOI: 10.1371/journal.pone.0343768 · PLOS One · 2026-03-25

## TL;DR

High-density lipoprotein cholesterol (HDL-C) levels have a U-shaped relationship with cognitive function in older adults in China.

## Contribution

The study reveals a nonlinear, U-shaped association between HDL-C levels and cognitive scores in aging populations.

## Key findings

- Very high HDL-C levels are linked to lower cognitive scores in older adults.
- A turning point at 67.43 mg/dL marks a shift from beneficial to harmful effects of HDL-C on cognition.

## Abstract

This study investigated the association between high-density lipoprotein cholesterol (HDL-C) levels and the risk of cognitive disorders in older adults. Data were obtained from the 2011 Chinese Health and Retirement Longitudinal Study and included 7,509 participants. Cognitive function was assessed using a scale that measured episodic memory and mental status. Statistical analyses included multiple linear regression, restricted cubic splines, and threshold effect analysis to explore the relationship between HDL-C levels and cognitive scores. Compared with Q1 (<35 mg/dL), very high HDL-C was associated with lower cognitive scores (Q4: β = −0.622 [95% CI, −0.908 to −0.337]; Q5: β = −0.322 [−0.627 to −0.017]). A U-shaped association was observed, with a turning point at 67.43 mg/dL. Below the threshold, a 1-SD higher HDL-C was associated with a 0.08-SD higher cognitive score (β = +0.08; 95% CI, 0.06–0.11; p < 0.001), whereas above the threshold a 1-SD higher HDL-C was associated with a 0.07-SD lower score (β = −0.07; 95% CI, −0.14 to −0.01; p = 0.019). Therefore, the relationship between lipid profiles and cognitive health is nuanced and nonlinear. Understanding these complexities is crucial for developing strategies to maintain cognitive function in older adults.

## Full-text entities

- **Genes:** APOE (apolipoprotein E) [NCBI Gene 348] {aka AD2, APO-E, ApoE4, LDLCQ5, LPG}, PON1 (paraoxonase 1) [NCBI Gene 5444] {aka ESA, MVCD5, PON}, ABCG1 (ATP binding cassette subfamily G member 1) [NCBI Gene 9619] {aka ABC8, WHITE1}, APOA1 (apolipoprotein A1) [NCBI Gene 335] {aka AMYLD3, HPALP2, apo(a)}, SCARB1 (scavenger receptor class B member 1) [NCBI Gene 949] {aka CD36L1, CLA-1, CLA1, HDLCQ6, HDLQTL6, SR-BI}, ABCA1 (ATP binding cassette subfamily A member 1) [NCBI Gene 19] {aka ABC-1, ABC1, CERP, HDLCQTL13, HDLDT1, HPALP1}
- **Diseases:** musculoskeletal disorders (MESH:D009140), CHARLS (OMIM:603663), brain inflammation (MESH:D004660), dementia (MESH:D003704), Age (MESH:D019588), clinical (MESH:D000075902), depression (MESH:D003866), cancer (MESH:D009369), death (MESH:D003643), hypertension (MESH:D006973), cardiovascular and cerebrovascular diseases (MESH:D002318), Alzheimer's disease (MESH:D000544), neuroinflammatory (MESH:D000090862), gastroesophageal and liver cancers (MESH:D006528), Cognitive impairment (MESH:D003072), digestive system cancers (MESH:D004067), neurotoxicity (MESH:D020258), chronic renal illness (MESH:D051436), atherosclerosis (MESH:D050197), diabetes (MESH:D003920), traumatic brain damage (MESH:D000070642), chronic inflammation (MESH:D007249), thrombotic (MESH:D013927), neurodegenerative disorders (MESH:D019636)
- **Chemicals:** cholesterol (MESH:D002784), EDTA-K2 (-), alcohol (MESH:D000438), sphingomyelin (MESH:D013109), triglyceride (MESH:D014280), lipid (MESH:D008055)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

45 references — full list in the complete paper: https://tomesphere.com/paper/PMC13016325/full.md

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Source: https://tomesphere.com/paper/PMC13016325