Abstract
BackgroundPrevious studies regarding the cholesterol-cognition relationship in midlife have generated conflicting results. We thus investigated whether dietary and blood cholesterol were associated with cognitive decline.MethodsParticipants were drawn from a large cohort study entitled the Effects and Mechanism Investigation of Cholesterol and Oxysterol on Alzheimer’s disease (EMCOA) study. We included 2514 participants who completed a selection of comprehensive cognitive tests and were followed for an average of 2.3 years. Blood concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) were assessed and dietary intakes were investigated by food frequency questionnaire (FFQ) at baseline. Apolipoprotein E (APOE) was genotyped by Kompetitive Allele Specific PCR (KASP) sequencing. Non-high-density lipoprotein cholesterol (Non-HDL-C) and LDL-C/HDL-C ratio were calculated. The longitudinal effects of dietary and blood cholesterol on risk of global cognitive decline (decrease in Montreal Cognitive Assessment (MoCA) > 2 points) were examined using Cox proportional hazards models. The nonlinear associations with global and domain-specific cognitive decline was evaluated with mixed effect linear models.ResultsIn Cox proportional hazards models, neither cholesterol nor egg intake was associated with a higher risk of accelerated global cognitive decline. In contrast, the higher serum concentrations of TC, LDL-C, non-HDL-C and LDL-C/HDL-C ratio were positively associated with accelerated global cognitive decline regardless of being evaluated continuously or categorically while higher HDL-C was positively associated with accelerated global cognitive decline only when being evaluated categorically (all P < 0.05). In mixed effect linear models, quadratic and longitudinal relations of dietary cholesterol and egg intakes to global cognition, processing speed and executive function were observed. Moreover, there were inverted U-shaped relations of HDL-C, with processing speed and executive function but U-shaped relations of HDL-C and LDL-C/HDL-C ratio with verbal memory. Adverse linear associations of higher LDL-C and LDL-C/HDL-C ratio with multiple cognitive comes were also revealed. Additionally adjusting for APOE genotype did not modify cholesterol-cognition associations. Dietary and serum cholesterol had variable associations with global and domain-specific cognitive decline across educational groups.ConclusionDifferential associations between dietary/serum cholesterol and cognitive decline across different domains of function were observed in a particular population of middle-aged and elderly Chinese. Interventions to improve cognitive reserve regarding dietary instruction and lipid management should be tailored according to specific target.Trial registrationEMCOA, ChiCTR-OOC-17011882, Registered 5th, July 2017-Retrospectively registered, http://www.medresman.org/uc/project/projectedit.aspx?proj=2610
Highlights
Previous studies regarding the cholesterol-cognition relationship in midlife have generated conflicting results
With respect to dietary cholesterol, Vincent et al [11] have indicated from meta-regression analyses that there is a positive, nonlinear relation between the changes in low-density lipoprotein cholesterol (LDL-C) and dietary cholesterol, suggesting a complex network of interrelationships between dietary cholesterol, serum cholesterol, which may obscure the role of dietary cholesterol in cognitive function
We aimed to examine potential quadratic relations of multiple serum cholesterol levels (TC, TG, high-density lipoprotein cholesterol (HDL-C) and LDL-C), cholesterol and egg intake to global and domain-specific cognitive decline, which may be more sensitive and helpful to elucidate the impacts of cholesterol on brain integrity and function
Summary
Previous studies regarding the cholesterol-cognition relationship in midlife have generated conflicting results. Higher serum cholesterol levels were associated with an increased risk of late-life cognitive decline, AD and other dementia. This risk relationship has not been extended to late life. Prior studies of increased late-life serum cholesterol and subsequent risk of incident cognitive dysfunction report either null results or protective associations [6]. A non-linear pattern of both high and low serum cholesterol is related to increased risk of cognitive decline or AD have been noted. Wendell et al have observed non-linear longitudinal [8] and cross-sectional [9] associations between serum cholesterol levels and cognitive function in Baltimore Longitudinal Study of Aging. Similar to serum cholesterol levels, associations of dietary cholesterol and cognitive impairment, AD or dementia are mixed, albeit limited [2, 12], suggesting a need for nonlinear examination
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