title: Differential associations of plasma lipids with incident dementia and dementia subtypes in the 3C Study: A longitudinal, population-based prospective cohort study.
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.
  
  
  RESULTS
  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.affiliation: University of Bordeaux, Bordeaux, France.|Inserm U1219, Bordeaux, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Schilling
authors.affiliation: University of Bordeaux, Bordeaux, France.|Inserm U1219, Bordeaux, France.|Department of Public Health, Bordeaux University Hospital, Bordeaux, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Tzourio
authors.affiliation: University of Bordeaux, Bordeaux, France.|Inserm U1219, Bordeaux, France.
authors.forename: Aïcha
authors.initials: A
authors.lastname: Soumaré
authors.affiliation: University of Bordeaux, Bordeaux, France.|Inserm U1219, Bordeaux, France.
authors.forename: Sara
authors.initials: S
authors.lastname: Kaffashian
authors.affiliation: University of Bordeaux, Bordeaux, France.|Inserm U1219, Bordeaux, France.|ISPED, University of Bordeaux, Bordeaux, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dartigues
authors.affiliation: Inserm U1061, Montpellier, France.|University of Montpellier, Montpellier, France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Ancelin
authors.affiliation: University of Bordeaux, Bordeaux, France.|Inserm U1219, Bordeaux, France.
authors.forename: Cécilia
authors.identifier: http://orcid.org/0000-0001-9809-7506
authors.initials: C
authors.lastname: Samieri
authors.affiliation: University of Bordeaux, Bordeaux, France.|Inserm U1219, Bordeaux, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Dufouil
authors.affiliation: 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.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Debette
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000453:epidemiology; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003704:Dementia / Q000097:blood / Q000453:epidemiology*; D015140:Dementia, Vascular / Q000097:blood / Q000453:epidemiology; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood*
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D002784:Cholesterol