Associations of Lipid Levels and Cognition: Findings from the Hispanic Community Health Study/Study of Latinos

Abstract

Objective:Hispanics/Latinos in the United States are less aware of their cholesterol levels and have a higher burden of associated adverse cardiovascular and cerebrovascular outcomes than non-Latino whites. Investigations of the associations between cholesterol levels and cognition in this population have often occurred within the context of metabolic syndrome and are limited to select lipids despite the fact that triglycerides (TGs) may be more relevant to the health of Hispanics/Latinos.Methods:Baseline data from the Hispanic Community Health Study/Study of Latinos, collected from 2008 to 2011, was used to investigate the associations of lipid levels (i.e., TG, total cholesterol, TC; low-density and high-density lipoprotein cholesterol, LDL-C and HDL-C) with cognition (i.e., learning, memory, verbal fluency, and digit symbol substitution, DSS), adjusting for relevant confounders.Results:In 7413 participants ages 45 to 74 years from Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American backgrounds, separate, fully adjusted linear regression models revealed that TG levels were inversely associated with DSS performance; however, this relationship was no longer significant once additional cardiovascular disease risk factors were added to the model (p = .06). TC and LDL-C levels (separately) were positively associated with learning and verbal fluency regardless of adjustments (p-values < .05). Separate analyses investigating the effect modification by background and sex revealed a particularly robust association between TC levels and DSS performance for Puerto Ricans and Central Americans (albeit in opposite directions) and an inverse relationship between TG levels and DSS performance for women (p-values < .02).Conclusions:It is important to consider individual lipid levels and demographic characteristics when investigating associations between cholesterol levels and cognition in Hispanics/Latinos.

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

“…In a study of HIV-infected men taking antiretroviral therapy, higher levels of LDL-C were associated with greater cognitive decline assessed by a cognitive summary score including the RAVLT (Mukerji et al, 2016). In contrast, a positive association between LDL-C levels and cognitive measures of learning and verbal fluency was reported in a cross-sectional analysis of the Hispanic Community Health Study/Study of Latinos (2008Latinos ( -2011 (Lamar et al, 2019). The overall evidence is conflicting about the relationship between serum lipids and brain lipids, and how these two are interconnected with cognition.…”

“…Model 3 included adjustment for covariates in Model 2 and statin, other lipid-lowering medication, and antidepressant medication use. Model covariates were chosen a priori based on previous studies examining the association between LDL-C and cognition, as well as clinical judgment (Gencer et al, 2020;Lamar et al, 2019;Yaffe et al, 2014). Tests for linear trend across LDL-C categories were calculated by modeling the LDL-C category as an ordinal variable.…”

“…However, randomized trials provide limited information on the association of long-term LDL-C levels with cognition as they typically provide only a few years of follow-up. Findings from observational studies that have investigated the association of LDL-C with or without lipid-lowering therapy and cognition have been mixed, but these studies have typically relied on a single measure of LDL-C at baseline (Benn, Nordestgaard, Frikke-Schmidt, & Tybjaerg-Hansen, 2017;Lamar et al, 2019;Mefford et al, 2018;Reitz, Tang, Luchsinger, & Mayeux, 2004;Shepardson, Shankar, & Selkoe, 2011;West et al, 2008). It is unclear whether long-term changes or therapeutic reductions in LDL-C over decades may affect cognitive function.…”

Genetic risk of dementia modifies the impact of obesity on limbic white matter and spatial navigation behavior in cognitively healthy adults

“…As myelin synthesis and maintenance are highly sensitive to cholesterol concentrations, and both APOE-e4 and obesity are associated with hypercholesterolemia 51 , it is also plausible that differences in cholesterol metabolism pathways may have contributed to our findings. Although cholesterol concentrations in the brain are largely independent of peripheral cholesterol levels, there is evidence of positive associations between WM microstructure and serum cholesterol 97 and cognition 98,99 . In contrast, hypercholesterolemia in older adults or the presence of other cardiovascular risk factors is associated with lower WM microstructure and increased risk of LOAD [99][100][101] .…”

“…Although cholesterol concentrations in the brain are largely independent of peripheral cholesterol levels, there is evidence of positive associations between WM microstructure and serum cholesterol 97 and cognition 98,99 . In contrast, hypercholesterolemia in older adults or the presence of other cardiovascular risk factors is associated with lower WM microstructure and increased risk of LOAD [99][100][101] . Positive associations between WM microstructure and allele dosage of the cholesterol gene CETP (cholesteryl ester transfer protein), which can influence the APOE-related risk of LOAD 102 , were also observed for young individuals whilst the opposite pattern was found for older adults 97 .…”