Association of mid-life serum lipid levels with late-life brain volumes: The atherosclerosis risk in communities neurocognitive study (ARIC–NCS)

Kasra Moazzami, Melinda C. Power, Rebecca Gottesman, Thomas Mosley, Pamela L. Lutsey, Clifford R. Jack, Ron C. Hoogeveen, Nancy West, David S. Knopman, Alvaro Alonso

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6 Scopus citations


Background: Limited information exists regarding the association between midlife lipid levels and late-life total and regional brain volumes. Methods: We studied 1872 participants in the longitudinal community-based Atherosclerosis Risk in Communities Neurocognitive Study. Serum lipid levels were measured in 1987–1989 (mean age, 53 ± 5 years). Participants underwent 3T brain MRI scans in 2011–2013. Brain volumes were measured using FreeSurfer image analysis software. Linear regression models were used to assess the associations between serum lipids and brain volumes modeled in standard deviation (SD) units, adjusting for potential confounders. Results: In adjusted analyses, one SD higher low-density lipoprotein cholesterol (LDL) levels were associated with larger total brain volumes (β 0.033, 95% CI 0.006–0.060) as well as larger volumes of the temporal (β 0.038, 95% CI 0.003–0.074) and parietal lobes (β 0.044, 95% CI 0.009–0.07) and Alzheimer disease-related region (β 0.048, 95% CI 0.048–0.085). Higher triglyceride levels were associated with smaller total brain volumes (β -0.033, 95% CI -0.060, -0.007). The associations between LDL levels and brain volumes were modified by age (P for interaction <0.001), with higher LDL levels associated with larger total and regional brain volumes only among adults >53 years at baseline, and were attenuated after application of weights to account for informative attrition, although associations with the parietal and Alzheimer's disease-related region remained significant. High-density lipoprotein cholesterol was not associated with brain volumes. Conclusion: Higher LDL levels in late midlife were associated with larger brain volumes later in life, while higher triglyceride levels were associated with smaller brain volumes. These associations were driven by adults >53 years at baseline.

Original languageEnglish (US)
Article number117324
StatePublished - Dec 2020

Bibliographical note

Funding Information:
The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung , and Blood Institute contracts ( HHSN268201700001I , HHSN268201700002I , HHSN268201700003I , HHSN268201700005I , HHSN268201700004I ). Neurocognitive data is collected by 2U01HL096812, 2U01HL096814, 2U01HL096899, 2U01HL096902, 2U01HL096917 from the NIH (NHLBI, NINDS, NIA and NIDCD), and with previous brain MRI examinations funded by R01-HL70825 from the NHLBI. Additional support was provided by American Heart Association award 16EIA26410001 (Alonso) and the National Institutes of Health awards T32 HL130025 (Moazzami) and K24HL148521 (Alonso).

Publisher Copyright:
© 2020


  • Brain volume
  • Lipid levels
  • Triglyceride


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