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

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.