Lipid trajectories improve risk models for Alzheimer’s disease and mild cognitive impairment
In this retrospective, case-control study, we tested the hypothesis that blood-lipid concentrations during the decade prior to cognitive symptom onset can inform risk prediction for Alzheimer's disease (AD) and stable mild cognitive impairment (MCI). Clinically well-characterized cases were dia...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227524002190 |
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| author | Bruce A. Chase Roberta Frigerio Chad J. Yucus Smita Patel Demetrius Maraganore Alan R. Sanders Jubao Duan Katerina Markopoulou |
| author_facet | Bruce A. Chase Roberta Frigerio Chad J. Yucus Smita Patel Demetrius Maraganore Alan R. Sanders Jubao Duan Katerina Markopoulou |
| author_sort | Bruce A. Chase |
| collection | DOAJ |
| description | In this retrospective, case-control study, we tested the hypothesis that blood-lipid concentrations during the decade prior to cognitive symptom onset can inform risk prediction for Alzheimer's disease (AD) and stable mild cognitive impairment (MCI). Clinically well-characterized cases were diagnosed using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria; MCI cases had been stable for ≥5 years; and controls were propensity matched to cases at symptom onset (MCI: 116 cases, 435 controls; AD: 215 cases, 483 controls). Participants were grouped based on (i) longitudinal trajectories and (ii) quintile of variability independent of the mean (VIM) for total cholesterol, HDL-C, low-density lipoprotein cholesterol, non-HDL-C, and ln(triglycerides). Risk models evaluated the contributions of lipid trajectory and VIM groups relative to APOE genotype or polygenic risk scores (PRSs) for AD and lipid levels and major lipoprotein confounders: age, lipid-lowering medications, comorbidities, and other longitudinal correlates of blood-lipid concentrations. In models with AD-PRS, higher MCI-risk was associated with the two lower HDL-C trajectories [odds ratios: 3.8(1.3−11.3; P = 0.014), 3.2(1.1−9.3; P = 0.038), relative to the high trajectory], and the lowest VIM quintile of non-HDL-C [odds ratio: 2.2 (1.3−3.8: P = 0.004), relative to quintiles 2−5]. Higher AD-risk was associated with the two lower HDL-C trajectories [odds ratios: 2.8(1.5−5.1; P = 0.001), 3.7 (2.0−7.0; P < 0.001)], and the lowest VIM quintile of total cholesterol [odds ratio: 2.5(1.5−4.0: P < 0.001)]. Inclusion of lipid-trajectory and VIM groups improved risk-model predictive performance independent of APOE and AD or lipid-level PRSs, providing important real-world perspectives on how longitudinal levels and variation of blood-lipid concentrations contribute to risk of cognitive decline. |
| format | Article |
| id | doaj-art-2404d0d661534f27b1d8b468c14e97ef |
| institution | Kabale University |
| issn | 0022-2275 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Journal of Lipid Research |
| spelling | doaj-art-2404d0d661534f27b1d8b468c14e97ef2025-01-30T05:12:38ZengElsevierJournal of Lipid Research0022-22752025-01-01661100714Lipid trajectories improve risk models for Alzheimer’s disease and mild cognitive impairmentBruce A. Chase0Roberta Frigerio1Chad J. Yucus2Smita Patel3Demetrius Maraganore4Alan R. Sanders5Jubao Duan6Katerina Markopoulou7Information Technology, Endeavor Health, Skokie, IL, USA; Pritzker School of Medicine, Chicago, USA; For correspondence: Bruce A. ChasePritzker School of Medicine, Chicago, USA; Research Institute, Endeavor Health, Evanston, IL, USADepartment of Neurology, Endeavor Health, Evanston, IL, USADepartment of Neurology, Endeavor Health, Evanston, IL, USADepartment of Neurology, Tulane University School of Medicine, New Orleans, LA, USACenter for Psychiatric Genetics, Endeavor Health Research Institute, Evanston, IL, USA; Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USACenter for Psychiatric Genetics, Endeavor Health Research Institute, Evanston, IL, USA; Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USADepartment of Neurology, Endeavor Health, Evanston, IL, USA; Department of Neurology, Pritzker School of Medicine, University of Chicago, Chicago, IL, USAIn this retrospective, case-control study, we tested the hypothesis that blood-lipid concentrations during the decade prior to cognitive symptom onset can inform risk prediction for Alzheimer's disease (AD) and stable mild cognitive impairment (MCI). Clinically well-characterized cases were diagnosed using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria; MCI cases had been stable for ≥5 years; and controls were propensity matched to cases at symptom onset (MCI: 116 cases, 435 controls; AD: 215 cases, 483 controls). Participants were grouped based on (i) longitudinal trajectories and (ii) quintile of variability independent of the mean (VIM) for total cholesterol, HDL-C, low-density lipoprotein cholesterol, non-HDL-C, and ln(triglycerides). Risk models evaluated the contributions of lipid trajectory and VIM groups relative to APOE genotype or polygenic risk scores (PRSs) for AD and lipid levels and major lipoprotein confounders: age, lipid-lowering medications, comorbidities, and other longitudinal correlates of blood-lipid concentrations. In models with AD-PRS, higher MCI-risk was associated with the two lower HDL-C trajectories [odds ratios: 3.8(1.3−11.3; P = 0.014), 3.2(1.1−9.3; P = 0.038), relative to the high trajectory], and the lowest VIM quintile of non-HDL-C [odds ratio: 2.2 (1.3−3.8: P = 0.004), relative to quintiles 2−5]. Higher AD-risk was associated with the two lower HDL-C trajectories [odds ratios: 2.8(1.5−5.1; P = 0.001), 3.7 (2.0−7.0; P < 0.001)], and the lowest VIM quintile of total cholesterol [odds ratio: 2.5(1.5−4.0: P < 0.001)]. Inclusion of lipid-trajectory and VIM groups improved risk-model predictive performance independent of APOE and AD or lipid-level PRSs, providing important real-world perspectives on how longitudinal levels and variation of blood-lipid concentrations contribute to risk of cognitive decline.http://www.sciencedirect.com/science/article/pii/S0022227524002190Alzheimer’s diseasecholesterolLDLlipidstriglyceridesHDL-C |
| spellingShingle | Bruce A. Chase Roberta Frigerio Chad J. Yucus Smita Patel Demetrius Maraganore Alan R. Sanders Jubao Duan Katerina Markopoulou Lipid trajectories improve risk models for Alzheimer’s disease and mild cognitive impairment Journal of Lipid Research Alzheimer’s disease cholesterol LDL lipids triglycerides HDL-C |
| title | Lipid trajectories improve risk models for Alzheimer’s disease and mild cognitive impairment |
| title_full | Lipid trajectories improve risk models for Alzheimer’s disease and mild cognitive impairment |
| title_fullStr | Lipid trajectories improve risk models for Alzheimer’s disease and mild cognitive impairment |
| title_full_unstemmed | Lipid trajectories improve risk models for Alzheimer’s disease and mild cognitive impairment |
| title_short | Lipid trajectories improve risk models for Alzheimer’s disease and mild cognitive impairment |
| title_sort | lipid trajectories improve risk models for alzheimer s disease and mild cognitive impairment |
| topic | Alzheimer’s disease cholesterol LDL lipids triglycerides HDL-C |
| url | http://www.sciencedirect.com/science/article/pii/S0022227524002190 |
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