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Differential associations of plasma lipids with incident dementia and dementia subtypes in the 3C Study: A longitudinal, population-based prospective cohort study.
PLoS Med 2017; 14(3):e1002265PM

Abstract

BACKGROUND

Vascular risk factors have been proposed as important targets for the prevention of dementia. As lipid fractions represent easily modifiable targets, we examined the longitudinal relationship of baseline lipid fractions with 13-y incident dementia and its subtypes (Alzheimer disease [AD] and mixed or vascular dementia) in older community-dwelling persons.

METHODS AND FINDINGS

Non-institutionalized persons aged 65+ y (n = 9,294) were recruited for the Three-City Study (3C Study), a population-based cohort study from the electoral rolls of the cities of Dijon, Bordeaux, and Montpellier, France, between March 1999 and March 2001. Follow-up examinations were performed every 2 y after the baseline assessment. The final study sample comprised 7,470 participants from the 3C Study (mean age ± standard deviation [SD] 73.8 ± 5.3 y, 61.0% women) who were prospectively followed up for up to 13 y. Fasting lipid fractions (triglycerides [TGs], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], total cholesterol [TC]) were studied as continuous variables, and results are reported per SD increase of each lipid fraction. Incident dementia and its subtypes were studied as censored variables using Cox models with age as time scale. Analyses were adjusted for sex, study center, and educational level, as well as vascular risk factors and apolipoprotein E (APOE) ε4 genotype. We corrected for multiple testing, yielding a significance threshold of 0.0169. p-Values above the significance threshold but less than 0.05 were considered nominally significant. During a mean (± SD) follow-up period of 7.9 ± 3.6 y, 779 participants developed incident dementia (n = 532 AD and n = 154 mixed or vascular dementia). Higher LDL-C and TC concentrations at baseline were associated with an increased risk of AD (hazard ratio [HR] per SD increase = 1.13 [95% CI 1.04-1.22], p = 0.0045, and HR = 1.12 [1.03-1.22], p = 0.0072, respectively). These associations were largely unchanged after adjustment for vascular risk factors and were attenuated after adjustment for APOEε4 (HR per SD increase = 1.12 [1.03-1.23], p = 0.0110, and HR = 1.12 [1.02-1.23], p = 0.0171, respectively). Higher TG concentrations at baseline were associated with an increased risk of all dementia (HR per SD increase = 1.11 [1.03-1.19], p = 0.0044) and mixed or vascular dementia (HR = 1.21 [1.04-1.41], p = 0.0163). However, these associations disappeared after adjusting for vascular risk factors (HR = 1.07 [0.98-1.17], p = 0.1374, and HR = 1.17 [0.96-1.42], p = 0.1206, respectively). Main limitations of the study include interval censoring of incident dementia cases, potential selective survival bias, and the fact that variation in lipid concentrations during follow-up could not be accounted for in the analyses.

CONCLUSIONS

In a large population-based sample of older community-dwelling persons with up to 13 y of follow-up, we observed that higher LDL-C and TC concentrations were associated with an increased risk of AD. This result was independent of vascular risk factors and was attenuated after adjustment for APOEε4 carrier status. TG and HDL-C concentrations were not associated with risk of incident dementia or its subtypes after accounting for vascular risk factors.

Authors+Show Affiliations

University of Bordeaux, Bordeaux, France. Inserm U1219, Bordeaux, France.University of Bordeaux, Bordeaux, France. Inserm U1219, Bordeaux, France. Department of Public Health, Bordeaux University Hospital, Bordeaux, France.University of Bordeaux, Bordeaux, France. Inserm U1219, Bordeaux, France.University of Bordeaux, Bordeaux, France. Inserm U1219, Bordeaux, France.University of Bordeaux, Bordeaux, France. Inserm U1219, Bordeaux, France. ISPED, University of Bordeaux, Bordeaux, France.Inserm U1061, Montpellier, France. University of Montpellier, Montpellier, France.University of Bordeaux, Bordeaux, France. Inserm U1219, Bordeaux, France.University of Bordeaux, Bordeaux, France. Inserm U1219, Bordeaux, France.University of Bordeaux, Bordeaux, France. Inserm U1219, Bordeaux, France. Memory Clinic, Department of Neurology, Bordeaux University Hospital, Bordeaux, France. Framingham Heart Study, Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, United States of America.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28350817

Citation

Schilling, Sabrina, et al. "Differential Associations of Plasma Lipids With Incident Dementia and Dementia Subtypes in the 3C Study: a Longitudinal, Population-based Prospective Cohort Study." PLoS Medicine, vol. 14, no. 3, 2017, pp. e1002265.
Schilling S, Tzourio C, Soumaré A, et al. Differential associations of plasma lipids with incident dementia and dementia subtypes in the 3C Study: A longitudinal, population-based prospective cohort study. PLoS Med. 2017;14(3):e1002265.
Schilling, S., Tzourio, C., Soumaré, A., Kaffashian, S., Dartigues, J. F., Ancelin, M. L., ... Debette, S. (2017). Differential associations of plasma lipids with incident dementia and dementia subtypes in the 3C Study: A longitudinal, population-based prospective cohort study. PLoS Medicine, 14(3), pp. e1002265. doi:10.1371/journal.pmed.1002265.
Schilling S, et al. Differential Associations of Plasma Lipids With Incident Dementia and Dementia Subtypes in the 3C Study: a Longitudinal, Population-based Prospective Cohort Study. PLoS Med. 2017;14(3):e1002265. PubMed PMID: 28350817.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential associations of plasma lipids with incident dementia and dementia subtypes in the 3C Study: A longitudinal, population-based prospective cohort study. AU - Schilling,Sabrina, AU - Tzourio,Christophe, AU - Soumaré,Aïcha, AU - Kaffashian,Sara, AU - Dartigues,Jean-François, AU - Ancelin,Marie-Laure, AU - Samieri,Cécilia, AU - Dufouil,Carole, AU - Debette,Stéphanie, Y1 - 2017/03/28/ PY - 2016/10/07/received PY - 2017/02/14/accepted PY - 2017/3/29/entrez PY - 2017/3/30/pubmed PY - 2019/3/21/medline SP - e1002265 EP - e1002265 JF - PLoS medicine JO - PLoS Med. VL - 14 IS - 3 N2 - BACKGROUND: Vascular risk factors have been proposed as important targets for the prevention of dementia. As lipid fractions represent easily modifiable targets, we examined the longitudinal relationship of baseline lipid fractions with 13-y incident dementia and its subtypes (Alzheimer disease [AD] and mixed or vascular dementia) in older community-dwelling persons. METHODS AND FINDINGS: Non-institutionalized persons aged 65+ y (n = 9,294) were recruited for the Three-City Study (3C Study), a population-based cohort study from the electoral rolls of the cities of Dijon, Bordeaux, and Montpellier, France, between March 1999 and March 2001. Follow-up examinations were performed every 2 y after the baseline assessment. The final study sample comprised 7,470 participants from the 3C Study (mean age ± standard deviation [SD] 73.8 ± 5.3 y, 61.0% women) who were prospectively followed up for up to 13 y. Fasting lipid fractions (triglycerides [TGs], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], total cholesterol [TC]) were studied as continuous variables, and results are reported per SD increase of each lipid fraction. Incident dementia and its subtypes were studied as censored variables using Cox models with age as time scale. Analyses were adjusted for sex, study center, and educational level, as well as vascular risk factors and apolipoprotein E (APOE) ε4 genotype. We corrected for multiple testing, yielding a significance threshold of 0.0169. p-Values above the significance threshold but less than 0.05 were considered nominally significant. During a mean (± SD) follow-up period of 7.9 ± 3.6 y, 779 participants developed incident dementia (n = 532 AD and n = 154 mixed or vascular dementia). Higher LDL-C and TC concentrations at baseline were associated with an increased risk of AD (hazard ratio [HR] per SD increase = 1.13 [95% CI 1.04-1.22], p = 0.0045, and HR = 1.12 [1.03-1.22], p = 0.0072, respectively). These associations were largely unchanged after adjustment for vascular risk factors and were attenuated after adjustment for APOEε4 (HR per SD increase = 1.12 [1.03-1.23], p = 0.0110, and HR = 1.12 [1.02-1.23], p = 0.0171, respectively). Higher TG concentrations at baseline were associated with an increased risk of all dementia (HR per SD increase = 1.11 [1.03-1.19], p = 0.0044) and mixed or vascular dementia (HR = 1.21 [1.04-1.41], p = 0.0163). However, these associations disappeared after adjusting for vascular risk factors (HR = 1.07 [0.98-1.17], p = 0.1374, and HR = 1.17 [0.96-1.42], p = 0.1206, respectively). Main limitations of the study include interval censoring of incident dementia cases, potential selective survival bias, and the fact that variation in lipid concentrations during follow-up could not be accounted for in the analyses. CONCLUSIONS: In a large population-based sample of older community-dwelling persons with up to 13 y of follow-up, we observed that higher LDL-C and TC concentrations were associated with an increased risk of AD. This result was independent of vascular risk factors and was attenuated after adjustment for APOEε4 carrier status. TG and HDL-C concentrations were not associated with risk of incident dementia or its subtypes after accounting for vascular risk factors. SN - 1549-1676 UR - https://www.unboundmedicine.com/medline/citation/28350817/Differential_associations_of_plasma_lipids_with_incident_dementia_and_dementia_subtypes_in_the_3C_Study:_A_longitudinal_population_based_prospective_cohort_study_ L2 - http://dx.plos.org/10.1371/journal.pmed.1002265 DB - PRIME DP - Unbound Medicine ER -