Statin use moderates APOE's and CRP's associations with dementia and is associated with lesser dementia severity in ε4 carriers

Abstract INTRODUCTION We tested the effect of statins on C‐reactive protein (CRP) and apolipoprotein E ( APOE )'s associations with dementia severity. METHODS A total of 1725 participants of the Alzheimer's Disease Neuroimaging Initiative (ADNI) were assigned from 12‐month follow‐up data into the following groups: (1) ε4 (–)/statin (–), (2) ε4 (–)/statin (+), (3) ε4 (+)/statin (–), and (4) ε4 (+)/statin (+). Dementia severity was assessed by a δ homolog: “dHABS.” A mediation model was stratified on statin use and moderation effects tested by a chi‐square difference. RESULTS Plasma CRP level decreased with ε4 allelic dose. Statins had no effect on the dHABS d‐score in non‐carriers but were associated with better scores in carriers. Treated carriers did not have more severe dementia than non‐carriers. Statin use moderated the mutual adjusted effects of APOE and CRP. CRP was not a mediator of APOE's effect. DISCUSSION Statins may provide a protective effect on the dementia severity of ε4 carriers. Highlights δ is a dementia‐specific phenotype related to general intelligence “ g ” and is assessed via a “d‐score.” Apolipoprotein E ( APOE ) and plasma C‐reactive protein (CRP) are independently associated with δ. Plasma CRP decreases with ε4 allelic dose. Statins were associated with better (less demented) d‐scores in ε4 carriers but had no effect in non‐ε4 carriers. Treated ε4 carriers did not have more severe dementia than non‐carriers. Statin use moderated the effects of APOE and CRP on δ. CRP was not a mediator of APOE's effect on δ.