The influence of ApoE4 on clinical progression of dementia: a meta-analysis.
OBJECTIVE
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 = 0.02; 95% C.-I.: -0.09 to 0.14; p = 0.67) or mortality (random-model pooled odds ratio = 0.74; 95% C.-I.: 0.36 to 1.53; p = 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.


CONCLUSIONS
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.
Allan
Charlotte L
CL
Department of Psychiatry, University of Oxford, Oxford, UK. Charlotte.allan@psych.ox.ac.uk
Ebmeier
Klaus P
KP
D053327:Apolipoprotein E4 / Q000235:genetics*; D015415:Biomarkers; D003704:Dementia / Q000235:genetics* / Q000401:mortality; D018450:Disease Progression; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D012307:Risk Factors
D053327:Apolipoprotein E4; D015415:Biomarkers