Low-Density Lipoprotein Cholesterol and Alzheimer's Disease: A Systematic Review and Meta-Analysis

Abstract

Objective: To assess the association between low-density lipoprotein cholesterol (LDL-c) and risk of Alzheimer's disease (AD).Methods: Embase, Pubmed, and Web of Science were searched until June 2019. Standard mean difference (SMD) with 95% confidence intervals (CI) was estimated using random-effects models.Results: Our meta-analysis of 26 studies revealed higher levels of LDL-c in AD than that of non-dementia controls (SMD = 0.35, 95% CI 0.12-0.58, p < 0.01). The meta-regression analysis on confounders showed that age (p < 0.01, Adj R-squared = 92.41%) and cardiovascular disease (p = 0.01, Adj R-squared = 85.21%), but not the body mass index, education, smoking, hypertension and diabetes mellitus, exerted an impact on the relationship between LDL-c and risk of ICH. Further subgroup analysis of age showed LDL-c levels in AD patients aged 60-70 were higher than that of non-dementia (60 ≤ age < 70: SMD = 0.80, 95% CI 0.23-1.37, p < 0.01); but no association between the SMD of AD in LDL-c and age over 70 was noted across the studies (70 ≤ age < 77: SMD = −0.02, 95% CI −0.39∼0.34, p = 9.0; 77 ≤ age < 80: SMD = 0.15, 95% CI −0.17∼0.47, p = 0.35; ≥80: SMD = 0.53, 95% CI −0.04∼1.11, p = 0.07). The concentrations of LDL-c during the quintile interval of 3∼4 were positively associated with AD (121 ≤ concentration < 137: SMD = 0.98, 95% CI 0.13∼1.82, p = 0.02; ≥137: SMD = 0.62, 95% CI 0.18∼1.06, p < 0.01); whereas there was no correlation between AD and LDL-c within the quintile interval of 1∼2 (103.9 ≤ concentration < 112: SMD = 0.08, 95% CI −0.20∼0.35, p = 0.59; 112 ≤ concentration < 121: SMD = −0.26, 95% CI −0.58∼0.06, p = 0.11). Conclusions: Elevated concentration of LDL-c (>121 mg/dl) may be a potential risk factor for AD. This association is strong in patients aged 60-70 years, but vanishes with advancing age.

Cholesterol and Alzheimer’s Disease Risk: A Meta-Meta-Analysis

“…The first study conducted by Zhou et al [ 33 ] provided information of K = 20 studies that compared serum LDL-C levels in AD and HC subjects ( N = 7033 participants: 2266 AD and 4767 HCs). Liu et al [ 1 ] also compared AD ( n = 584 AD) and HC participants ( n = 2130), examining K = 9 independent studies with an N = 2714.…”

“…Four meta-analyses assessing the effects of mid-life serum cholesterol on late-life risk of dementia and AD have yielded conflicting results. Several studies state that high cholesterol levels in middle age represent a risk factor for AD, but that there are no detectable differences in cholesterol levels at advanced ages [ 33 , 35 , 46 ]. Therefore, the non-significant effects of TC on AD in prospective studies (30 years to follow-up) could be explained by the variations in TC levels and the disease progression.…”

Plasma Lipids as Biomarkers for Alzheimer's Disease: A Systematic Review

“…LDL-C is seen to cause vascular and neurotoxic effects in the brain [35,36]. Another study by Zhon, a systematic review including nearly 6500 patients, found the same association; however, LDL-C was high in patients with AD mostly around 60-70 years of age, gradually reduced with ageing [37]. Some studies found an association between AD and only LDL-C, TC.…”

A Fundamental Role for Oxidants and Intracellular Calcium Signals in Alzheimer’s Pathogenesis—And How a Comprehensive Antioxidant Strategy May Aid Prevention of This Disorder

“…Palmitic or stearic acid can activate microglia in vitro through a mechanism dependent on TLR4 [ 301 ]. And elevated low-density lipoprotein cholesterol (>121 mg/dL)—less common in those following vegan or Mediterranean diets—is associated with AD risk; whether this association is causative remains unclear [ 302 , 303 , 304 ]. (As a cautionary note—vegans would be well advised to supplement with DHA, Se, and of course vitamin B12).…”