Mendelian Randomization of Dyslipidemia on Cognitive Impairment Among Older Americans
Background: Altered lipid metabolism may be a risk factor for dementia, and blood cholesterol level has a strong genetic component. We tested the hypothesis that dyslipidemia (either low levels of high-density lipoprotein cholesterol (HDL-C) or high total cholesterol) is associated with cognitive st...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2021.660212/full |
| _version_ | 1818667909005705216 |
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| author | Mingzhou Fu Kelly M. Bakulski Cesar Higgins Erin B. Ware Erin B. Ware |
| author_facet | Mingzhou Fu Kelly M. Bakulski Cesar Higgins Erin B. Ware Erin B. Ware |
| author_sort | Mingzhou Fu |
| collection | DOAJ |
| description | Background: Altered lipid metabolism may be a risk factor for dementia, and blood cholesterol level has a strong genetic component. We tested the hypothesis that dyslipidemia (either low levels of high-density lipoprotein cholesterol (HDL-C) or high total cholesterol) is associated with cognitive status and domains, and assessed causality using genetic predisposition to dyslipidemia as an instrumental variable.Methods: Using data from European and African genetic ancestry participants in the Health and Retirement Study, we selected observations at the first non-missing biomarker assessment (waves 2006–2012). Cognition domains were assessed using episodic memory, mental status, and vocabulary tests. Overall cognitive status was categorized in three levels (normal, cognitive impairment non-dementia, dementia). Based on 2018 clinical guidelines, we compared low HDL-C or high total cholesterol to normal levels. Polygenic scores for dyslipidemia were used as instrumental variables in a Mendelian randomization framework. Multivariable logistic regressions and Wald-type ratio estimators were used to examine associations.Results: Among European ancestry participants (n = 8,781), at risk HDL-C levels were associated with higher odds of cognitive impairment (OR = 1.20, 95% CI: 1.03, 1.40) and worse episodic memory, specifically. Using cumulative genetic risk for HDL-C levels as a valid instrumental variable, a significant causal estimate was observed between at risk low HDL-C levels and higher odds of dementia (OR = 2.15, 95% CI: 1.16, 3.99). No significant associations were observed between total cholesterol levels and cognitive status. No significant associations were observed in the African ancestry sample (n = 2,101).Conclusion: Our study demonstrates low blood HDL-C is a potential causal risk factor for impaired cognition during aging in non-Hispanic whites of European ancestry. Dyslipidemia can be modified by changing diets, health behaviors, and therapeutic strategies, which can improve cognitive aging. Studies on low density lipoprotein cholesterol, the timing of cholesterol effects on cognition, and larger studies in non-European ancestries are needed. |
| first_indexed | 2024-12-17T06:27:54Z |
| format | Article |
| id | doaj.art-10159549f3724f8a890f29939a48105b |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-17T06:27:54Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-10159549f3724f8a890f29939a48105b2022-12-21T22:00:15ZengFrontiers Media S.A.Frontiers in Neurology1664-22952021-06-011210.3389/fneur.2021.660212660212Mendelian Randomization of Dyslipidemia on Cognitive Impairment Among Older AmericansMingzhou Fu0Kelly M. Bakulski1Cesar Higgins2Erin B. Ware3Erin B. Ware4Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, United StatesDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, United StatesDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, United StatesSurvey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, United StatesPopulation Studies Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, United StatesBackground: Altered lipid metabolism may be a risk factor for dementia, and blood cholesterol level has a strong genetic component. We tested the hypothesis that dyslipidemia (either low levels of high-density lipoprotein cholesterol (HDL-C) or high total cholesterol) is associated with cognitive status and domains, and assessed causality using genetic predisposition to dyslipidemia as an instrumental variable.Methods: Using data from European and African genetic ancestry participants in the Health and Retirement Study, we selected observations at the first non-missing biomarker assessment (waves 2006–2012). Cognition domains were assessed using episodic memory, mental status, and vocabulary tests. Overall cognitive status was categorized in three levels (normal, cognitive impairment non-dementia, dementia). Based on 2018 clinical guidelines, we compared low HDL-C or high total cholesterol to normal levels. Polygenic scores for dyslipidemia were used as instrumental variables in a Mendelian randomization framework. Multivariable logistic regressions and Wald-type ratio estimators were used to examine associations.Results: Among European ancestry participants (n = 8,781), at risk HDL-C levels were associated with higher odds of cognitive impairment (OR = 1.20, 95% CI: 1.03, 1.40) and worse episodic memory, specifically. Using cumulative genetic risk for HDL-C levels as a valid instrumental variable, a significant causal estimate was observed between at risk low HDL-C levels and higher odds of dementia (OR = 2.15, 95% CI: 1.16, 3.99). No significant associations were observed between total cholesterol levels and cognitive status. No significant associations were observed in the African ancestry sample (n = 2,101).Conclusion: Our study demonstrates low blood HDL-C is a potential causal risk factor for impaired cognition during aging in non-Hispanic whites of European ancestry. Dyslipidemia can be modified by changing diets, health behaviors, and therapeutic strategies, which can improve cognitive aging. Studies on low density lipoprotein cholesterol, the timing of cholesterol effects on cognition, and larger studies in non-European ancestries are needed.https://www.frontiersin.org/articles/10.3389/fneur.2021.660212/fullblood cholesterolpolygenic scoredementiaMendelian randomizationcognitive domain |
| spellingShingle | Mingzhou Fu Kelly M. Bakulski Cesar Higgins Erin B. Ware Erin B. Ware Mendelian Randomization of Dyslipidemia on Cognitive Impairment Among Older Americans Frontiers in Neurology blood cholesterol polygenic score dementia Mendelian randomization cognitive domain |
| title | Mendelian Randomization of Dyslipidemia on Cognitive Impairment Among Older Americans |
| title_full | Mendelian Randomization of Dyslipidemia on Cognitive Impairment Among Older Americans |
| title_fullStr | Mendelian Randomization of Dyslipidemia on Cognitive Impairment Among Older Americans |
| title_full_unstemmed | Mendelian Randomization of Dyslipidemia on Cognitive Impairment Among Older Americans |
| title_short | Mendelian Randomization of Dyslipidemia on Cognitive Impairment Among Older Americans |
| title_sort | mendelian randomization of dyslipidemia on cognitive impairment among older americans |
| topic | blood cholesterol polygenic score dementia Mendelian randomization cognitive domain |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2021.660212/full |
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