ApoE4 is a risk factor for the development of Alzheimer's disease, and has a functional role suggesting its importance in the neuropathology of dementia. We present a meta-analysis to investigate whether ApoE4 also affects the clinical progression of dementia in terms of cognitive decline or mortality. Methods: We searched Medline, Embase and PsychINFO from 1990 until April 2009, for case control or cohort studies which investigated the effect of ApoE4 on progression of dementia. We identified 427 studies; 17 were suitable for inclusion. In total, there were 1733 participants with dementia at baseline, of whom 975 were heterozygous or homozygous for ApoE4.
Results: There was no significant difference in cognitive decline (random-model effect size ΒΌ 0.02; 95% C.-I.: -0.09 to 0.14; p ΒΌ 0.67) or mortality (random-model pooled odds ratio ΒΌ 0.74; 95% C.-I.: 0.36 to 1.53; p ΒΌ 0.41) based on the presence of ApoE4. There was no significant heterogeneity between studies using cognitive decline as an outcome. In meta-regressions of cognitive decline, duration of symptoms, age, gender and frequency of participants with ApoE4 in the samples did not contribute to outcome. Conclusion: Different ApoE alleles do not modify the speed of clinical progression of dementia in a way that would be detectable in a sample of 1700 patients.