Academic Journal
Investigating causal effects of HDL-C on cognitive function through cross-sectional and Mendelian randomization analyses: concentration–response patterns and clues for Alzheimer's disease prevention.
| Τίτλος: | Investigating causal effects of HDL-C on cognitive function through cross-sectional and Mendelian randomization analyses: concentration–response patterns and clues for Alzheimer's disease prevention. |
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| Συγγραφείς: | Fan, Longmin, Jiang, Haitao, Zhang, Zheyu |
| Πηγή: | BioData Mining; 9/22/2025, Vol. 18 Issue 1, p1-17, 17p |
| Θεματικοί όροι: | HDL cholesterol, Cognitive ability, Gender inequality, Alzheimer's disease, Cholesterol, Cross-sectional method, Cognitive aging, Mendelian randomization |
| Περίληψη: | Background: Disrupted cholesterol homeostasis may accelerate cognitive aging. This study investigated the relationship between serum HDL-C levels and cognitive function, utilizing cross-sectional data and Mendelian randomization (MR) analysis. Methods: A cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2011–2014, including 19,931 participants. Among them, 2,777 individuals aged 60 years and older with complete HDL-C levels and cognitive function data were included. Cognitive function was assessed using tests such as the Consortium to Establish a Registry for Alzheimer's Disease Immediate and Delayed Recall, the Animal Fluency Test, and the Digit Symbol Substitution Test. Additionally, MR analysis was employed to assess the causal relationship between genetically predicted HDL-C and dementia. Results: Gender-stratified analyses revealed sex-specific patterns in the relationship between HDL-C and cognitive function. In fully adjusted linear models, men showed consistently positive associations across all cognitive domains, including delayed recall (β = 0.10, 95% CI 0.04–0.17, p < 0.001), immediate recall (β = 0.06, 95% CI 0.00–0.12, p = 0.047), verbal fluency (β = 0.20, 95% CI 0.14–0.26, p < 0.001), processing speed (β = 0.09, 95% CI 0.05–0.14, p < 0.001), and overall composite score (β = 0.45, 95% CI 0.29–0.62, p < 0.001). In women, these associations were attenuated or non-significant for immediate recall, delayed recall, and composite cognition, suggesting non-linearity. Further concentration–response analyses revealed a linear positive association in men and an inverted U-shaped relationship in women. MR analyses indicated a protective association between genetically predicted HDL-C and Alzheimer's disease risk (OR = 0.51, 95% CI 0.29–0.89, p = 0.019). However, sensitivity analyses revealed attenuation after MR-PRESSO outlier correction (β=-0.013, p = 0.756), and inconsistent estimates across methods, with significant heterogeneity (Q-test p < 0.001) and evidence of pleiotropy. In multivariable analysis, adjusting for LDL-C and TG, IVW (β = 0.290, p = 0.048) and Lasso regression (β = 0.752, p = 0.008) indicated weak positive correlations. However, MR-Egger (β = 0.752, p = 0.008) revealed potential pleiotropic interference (intercept p = 0.050). Conclusions: Our findings suggest that maintaining optimal serum HDL-C levels may help preserve cognitive function in older adults. Notably, sex-specific associations were observed, warranting further investigation into underlying mechanisms. [ABSTRACT FROM AUTHOR] |
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| Βάση Δεδομένων: | Biomedical Index |
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| Items | – Name: Title Label: Title Group: Ti Data: Investigating causal effects of HDL-C on cognitive function through cross-sectional and Mendelian randomization analyses: concentration–response patterns and clues for Alzheimer's disease prevention. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Fan%2C+Longmin%22">Fan, Longmin</searchLink><br /><searchLink fieldCode="AR" term="%22Jiang%2C+Haitao%22">Jiang, Haitao</searchLink><br /><searchLink fieldCode="AR" term="%22Zhang%2C+Zheyu%22">Zhang, Zheyu</searchLink> – Name: TitleSource Label: Source Group: Src Data: BioData Mining; 9/22/2025, Vol. 18 Issue 1, p1-17, 17p – Name: Subject Label: Subject Terms Group: Su Data: <searchLink fieldCode="DE" term="%22HDL+cholesterol%22">HDL cholesterol</searchLink><br /><searchLink fieldCode="DE" term="%22Cognitive+ability%22">Cognitive ability</searchLink><br /><searchLink fieldCode="DE" term="%22Gender+inequality%22">Gender inequality</searchLink><br /><searchLink fieldCode="DE" term="%22Alzheimer's+disease%22">Alzheimer's disease</searchLink><br /><searchLink fieldCode="DE" term="%22Cholesterol%22">Cholesterol</searchLink><br /><searchLink fieldCode="DE" term="%22Cross-sectional+method%22">Cross-sectional method</searchLink><br /><searchLink fieldCode="DE" term="%22Cognitive+aging%22">Cognitive aging</searchLink><br /><searchLink fieldCode="DE" term="%22Mendelian+randomization%22">Mendelian randomization</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Background: Disrupted cholesterol homeostasis may accelerate cognitive aging. This study investigated the relationship between serum HDL-C levels and cognitive function, utilizing cross-sectional data and Mendelian randomization (MR) analysis. Methods: A cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2011–2014, including 19,931 participants. Among them, 2,777 individuals aged 60 years and older with complete HDL-C levels and cognitive function data were included. Cognitive function was assessed using tests such as the Consortium to Establish a Registry for Alzheimer's Disease Immediate and Delayed Recall, the Animal Fluency Test, and the Digit Symbol Substitution Test. Additionally, MR analysis was employed to assess the causal relationship between genetically predicted HDL-C and dementia. Results: Gender-stratified analyses revealed sex-specific patterns in the relationship between HDL-C and cognitive function. In fully adjusted linear models, men showed consistently positive associations across all cognitive domains, including delayed recall (β = 0.10, 95% CI 0.04–0.17, p < 0.001), immediate recall (β = 0.06, 95% CI 0.00–0.12, p = 0.047), verbal fluency (β = 0.20, 95% CI 0.14–0.26, p < 0.001), processing speed (β = 0.09, 95% CI 0.05–0.14, p < 0.001), and overall composite score (β = 0.45, 95% CI 0.29–0.62, p < 0.001). In women, these associations were attenuated or non-significant for immediate recall, delayed recall, and composite cognition, suggesting non-linearity. Further concentration–response analyses revealed a linear positive association in men and an inverted U-shaped relationship in women. MR analyses indicated a protective association between genetically predicted HDL-C and Alzheimer's disease risk (OR = 0.51, 95% CI 0.29–0.89, p = 0.019). However, sensitivity analyses revealed attenuation after MR-PRESSO outlier correction (β=-0.013, p = 0.756), and inconsistent estimates across methods, with significant heterogeneity (Q-test p < 0.001) and evidence of pleiotropy. In multivariable analysis, adjusting for LDL-C and TG, IVW (β = 0.290, p = 0.048) and Lasso regression (β = 0.752, p = 0.008) indicated weak positive correlations. However, MR-Egger (β = 0.752, p = 0.008) revealed potential pleiotropic interference (intercept p = 0.050). Conclusions: Our findings suggest that maintaining optimal serum HDL-C levels may help preserve cognitive function in older adults. Notably, sex-specific associations were observed, warranting further investigation into underlying mechanisms. [ABSTRACT FROM AUTHOR] – Name: Abstract Label: Group: Ab Data: <i>Copyright of BioData Mining is the property of BioMed Central and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1186/s13040-025-00484-3 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 17 StartPage: 1 Subjects: – SubjectFull: HDL cholesterol Type: general – SubjectFull: Cognitive ability Type: general – SubjectFull: Gender inequality Type: general – SubjectFull: Alzheimer's disease Type: general – SubjectFull: Cholesterol Type: general – SubjectFull: Cross-sectional method Type: general – SubjectFull: Cognitive aging Type: general – SubjectFull: Mendelian randomization Type: general Titles: – TitleFull: Investigating causal effects of HDL-C on cognitive function through cross-sectional and Mendelian randomization analyses: concentration–response patterns and clues for Alzheimer's disease prevention. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Fan, Longmin – PersonEntity: Name: NameFull: Jiang, Haitao – PersonEntity: Name: NameFull: Zhang, Zheyu IsPartOfRelationships: – BibEntity: Dates: – D: 22 M: 09 Text: 9/22/2025 Type: published Y: 2025 Identifiers: – Type: issn-print Value: 17560381 Numbering: – Type: volume Value: 18 – Type: issue Value: 1 Titles: – TitleFull: BioData Mining Type: main |
| ResultId | 1 |