Long-Term Levels of LDL-C and Cognitive Function: The CARDIA Study

• Published in: Journal of the International Neuropsychological Society Vol. 27; no. 10; pp. 1048 - 1057
• Main Authors: Mefford, Matthew T., Chen, Ligong, Lewis, Cora E., Muntner, Paul, Sidney, Stephen, Launer, Lenore J., Monda, Keri L., Ruzza, Andrea, Kassahun, Helina, Rosenson, Robert S., Carson, April P.
• Format: Journal Article
• Language: English
• Published: New York, USA Cambridge University Press 01.11.2021
• Subjects: Adolescent; Adult; Alcohol use; Auditory discrimination learning; Blood flow; Blood pressure; Cardiovascular disease; Cerebral blood flow; Cholesterol; Cholesterol, LDL - blood; Cognition; Cognition & reasoning; Cognitive ability; Cohort analysis; Cohort Studies; Collaboration; Data collection; Diabetes; Epidemiology; Glucose; Humans; Lipids; Low density lipoprotein; Magnetic resonance imaging; Memory; Middle Aged; Neuroimaging; Product safety; Prospective Studies; Quality control; Regular Research; Sensory integration; Statins; Stroop Test; Substantia alba; Substantia grisea; Triglycerides; Visual discrimination learning; Young Adult; Lipids; Cognition; LDL; Cholesterol; Cohort studies
• ISSN: 1355-6177; 1469-7661
• DOI: 10.1017/S1355617721000059

It is uncertain if long-term levels of low-density lipoprotein-cholesterol (LDL-C) affect cognition in middle age. We examined the association of LDL-C levels over 25 years with cognitive function in a prospective cohort of black and white US adults. Lipids were measured at baseline (1985-1986; age: 18-30 years) and at serial examinations conducted over 25 years. Time-averaged cumulative LDL-C was calculated using the area under the curve for 3,328 participants with ≥3 LDL-C measurements and a cognitive function assessment. Cognitive function was assessed at the Year 25 examination with the Digit Symbol Substitution Test [DSST], Rey Auditory Visual Learning Test [RAVLT], and Stroop Test. A brain magnetic resonance imaging (MRI) sub-study (N = 707) was also completed at Year 25 to assess abnormal white matter tissue volume (AWMV) and gray matter cerebral blood flow volume (GM-CBFV) as secondary outcomes. There were 15.6%, 32.9%, 28.9%, and 22.6% participants with time-averaged cumulative LDL-C <100 mg/dL, 101-129 mg/dL, 130-159 mg/dL, and ≥160 mg/dL, respectively. Standardized differences in all cognitive function test scores ranged from 0.16 SD lower to 0.09 SD higher across time-averaged LDL-C categories in comparison to those with LDL-C < 100 mg/dL. After covariate adjustment, participants with higher versus lower time-averaged LDL-C had a lower RAVLT score (p-trend = 0.02) but no differences were present for DSST, Stroop Test, AWMV, or GM-CBFV. Cumulative LDL-C was associated with small differences in memory, as assessed by RAVLT scores, but not other cognitive or brain MRI measures over 25 years of follow-up.