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.
Highlights
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive and irreversible decline in cognition (Kapogiannis et al, 2019)
Six papers that used other diagnostic criteria but were substantially consistent with those we specified were included (Caramelli et al, 1999; Lesser et al, 2001; Solfrizzi et al, 2002; Macesic et al, 2017; Chen et al, 2019); (2) a measure of association was described for serum low-density lipoprotein cholesterol (LDL-c) to incident AD; (2) the mean levels of LDL-c in AD and non-dementia were recorded; (3) study design was case-control study; (4) the report with large sample was used if subjects came from one center
Stroke data from AD patients and non-dementia controls were insufficient for meta-regression analysis
Summary
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive and irreversible decline in cognition (Kapogiannis et al, 2019). The patients included in the above studies did not exclude the use of cholesterollowering drugs, which played vague role in pathogenesis of AD and might not represent the true LDL-c level of AD patients. Given these uncertainties and contradictions, it prompted us to conduct a meta-analysis of existing studies without the interference of cholesterol-lowering drugs to elucidate a more precise association between LDL-c and AD than individual studies, with the expectation of an aggregate estimate of AD risk for specified changes in serum LDL-c
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