Abstract Background and Aims Dementia is a leading cause of death and disability that shares risk factors with atherosclerotic cardiovascular disease (ASCVD). High lipoprotein(a) is a causal risk factor for ASCVD while results for dementia are conflicting. With lipoprotein(a) lowering drugs in clinical trial, we tested whether lipoprotein(a) associates with risk of Alzheimer’s disease (AD) and/or vascular-related dementia (VRD). Methods We included 539,478 individuals with plasma lipoprotein(a) measurements from three European prospective cohort studies of the general population. LPA KIV-2 number of repeats, which determines lipoprotein(a) isoform size inversely correlated with plasma lipoprotein(a) levels, were available in 117,029 from two of the cohorts. Individuals were followed for up to 30.2 years, during which 6,404 developed AD and 7,866 VRD. Statistical analyses accounted for competing risk of death, important for studies of dementia occurring late in life. Results On continuous scales, lipoprotein(a) levels did not associate with risk of AD or VRD. When accounting for competing risk of death, absolute risks of VRD increased with higher lipoprotein(a) levels in cohort #3 (N=458,601; events=5,132; p=0.01) (Figure 1), but not in the combined cohorts #1 and #2 (N=80,877; events=2,734; p=0.4) (Figure 2). In the combined cohorts #1 and #2, LPA KIV-2 number of repeats ≤5th vs. 50th percentiles associated with a hazard ratio for AD of 1.27(95%CI:1.08-1.48). Conclusion Low lipoprotein(a) levels did not associate with risk of AD or VRD, indicating that pharmacological lowering of lipoprotein(a) is likely safe for risk of dementia. We cannot exclude that very high lipoprotein(a) or small isoform size increases risk of dementia.Figure 1 Figure 2
Thomas et al. (Sat,) studied this question.