Low-Density Lipoprotein Cholesterol and Alzheimer's Disease: A Systematic Review and Meta-Analysis.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational studies
PubMed 32082137 · doi:10.3389/fnagi.2020.00005
What was done
A systematic review and random-effects meta-analysis evaluated the association between low-density lipoprotein cholesterol (LDL-c) and Alzheimer's disease (AD). Searches across Embase, PubMed, and Web of Science through June 2019 identified 26 studies comparing LDL-c levels between AD patients and non-dementia controls. Effect sizes were pooled as standardized mean differences (SMD) with 95% confidence intervals (CI), alongside meta-regression for potential confounders and subgroup analyses across age brackets and LDL-c concentration quintiles.
What was found
Across 26 studies, AD patients had higher LDL-c levels than non-dementia controls (SMD = 0.35, 95% CI 0.12 to 0.58, p < 0.01). Meta-regression indicated that age (p < 0.01, adjusted R² = 92.41%) and cardiovascular disease (p = 0.01, adjusted R² = 85.21%) modified the relationship, while BMI, education, smoking, hypertension, and diabetes did not. Subgroup analyses showed elevated LDL-c was significant only in patients aged 60–70 years (SMD = 0.80, 95% CI 0.23 to 1.37, p < 0.01), with no significant association in ages 70–<77 (SMD = -0.02, 95% CI -0.39 to 0.34, p = 9.0 [sic]), 77–<80 (SMD = 0.15, 95% CI -0.17 to 0.47, p = 0.35), or ≥80 (SMD = 0.53, 95% CI -0.04 to 1.11, p = 0.07). By quintile, LDL-c was positively associated with AD at 121–<137 mg/dL (SMD = 0.98, 95% CI 0.13 to 1.82, p = 0.02) and ≥137 mg/dL (SMD = 0.62, 95% CI 0.18 to 1.06, p < 0.01), but not below 121 mg/dL.
Why it matters
This review identifies a potential concentration threshold (>121 mg/dL) and suggests that the relationship between elevated LDL-c and AD is age-dependent, potentially clarifying inconsistencies across older cohorts.
Limits
The total number of human participants across the 26 studies is not reported in the abstract. Observational designs cannot establish causality, and the abstract does not report statin use, APOE ε4 genotype, or longitudinal timing of lipid measurements.
Cited by
- partial Failure to lower LDL cholesterol below 100 mg/dL or 70 mg/dL is associated with an increased risk of developing dementia.