Abstract INTRODUCTION We evaluated the independent associations between high‐density lipoprotein cholesterol (HDL‐C) and triglyceride (TG) levels with Alzheimer's disease and related dementias (ADRD). METHODS Among 177,680 members of Kaiser Permanente Northern California who completed a survey on health risks, we residualized TGs and HDL‐C conditional on age, sex, and body mass index. We included these residuals individually and concurrently in Cox models predicting ADRD incidence. RESULTS Low (hazard ratio [HR] 1…

Abstract INTRODUCTION Mixed evidence on how statin use affects risk of Alzheimer's disease and related dementias (ADRD) may reflect heterogeneity across sociodemographic factors. Few studies have sufficient power to evaluate effect modifiers. METHODS Kaiser Permanente Northern California (KPNC) members ( n = 705,061; n = 202,937 with sociodemographic surveys) who initiated statins from 2001 to 2010 were matched on age and low‐density lipoprotein cholesterol (LDL‐C) with non‐initiators and followed through 2020 for…

Abstract Purpose Pathogenic DEGS1 variants have been reported in individuals with autosomal recessive hypomyelinating leukodystrophy 18 (HLD18; MIM# 618404). We sought to resolve a 5′ +4/+5 splice site variant of uncertain significance found in three individuals with HLD features. Methods We used next-generation DNA and transcriptome sequencing, cell-based splicing assays, and tandem mass spectrometry to detect and characterize the splice site variant. We then performed RNA structure probing and conventional antis…

Abstract Background Polygenic risk scores derived from coronary artery disease genome-wide association studies are associated with statin relative risk reduction. Objective Examine the relationship between coronary artery disease polygenic risk scores that include variants below thresholds of genome-wide significance and statin primary prevention of major adverse cardiovascular events. Methods We generated coronary artery disease polygenic risk scores for participants with no past evidence of myocardial infarction…

This emulated trial provides Class II evidence that statin initiation is not associated with AD/ADRD or AD incidence after the first year of follow-up.