Statin use moderates APOE's and CRP's associations with dementia and is associated with lesser dementia severity in 4 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) epsilon 4 (-)/statin (-), (2) epsilon 4 (-)/statin (+), (3) epsilon 4 (+)/statin (-), and (4) epsilon 4 (+)/statin (+). Dementia severity was assessed by a delta 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 epsilon 4 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.DISCUSSIONS: tatins may provide a protective effect on the dementia severity of epsilon 4 carriers.Highlights delta 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 delta. Plasma CRP decreases with epsilon 4 allelic dose. Statins were associated with better (less demented) d-scores in epsilon 4 carriers but had no effect in non-epsilon 4 carriers. Treated epsilon 4 carriers did not have more severe dementia than non-carriers. Statin use moderated the effects of APOE and CRP on delta. CRP was not a mediator of APOE's effect on delta.