Apolipoprotein E and affective symptoms in mild cognitive impairment and Alzheimer’s disease dementia: A systematic review and meta-analysis

•APOE is not associated with affective symptoms in cognitively impaired subjects.•Studies assessing the affect-APOE relationship show large heterogeneity in design.•Contrasting prior findings could not be explained by this variation in study design. APOE status has been associated to affective symptoms in cognitively impaired subjects, with conflicting results. Databases CINAHL, Embase, PsychINFO and PubMed were searched for studies evaluating APOE genotype with affective symptoms in MCI and AD dementia. Symptoms were meta-analyzed separately and possible sources of heterogeneity were examined. Fifty-three abstracts fulfilled the eligibility criteria. No association was found between the individual symptoms and APOE ε4 carriership or zygosity. For depression and anxiety, only pooled unadjusted estimates showed positive associations with between-study heterogeneity, which could be explained by variation in study design, setting and way of symptom assessment. There is no evidence that APOE ε4 carriership or zygosity is associated with the presence of depression, anxiety, apathy, agitation, irritability or sleep disturbances in cognitively impaired subjects. Future research should shift its focus from this single polymorphism to a more integrated view of other biological factors.