Apolipoprotein E and dementia in Parkinson disease: A meta-analysis

Objective: To understand the relationship of apolipoprotein E (APOE) polymorphism to dementia in Parkinson disease (PD) because the APOE ε4 allele is linked to Alzheimer disease. Data Source: We reviewed MEDLINE, BIOSIS Previews, and ISI Web of Science from January 1, 1966, to May 7, 2004, supplemented by citation analysis from retrieved articles. Study Selection: Case-control studies using clinical or pathologic criteria for PD and dementia, and with complete APOE genotype frequencies data. Data Extraction: We compared estimated prevalence odds ratios for dementia in PD in relation to each allele. We also looked for evidence of heterogeneity and publication bias and performed a stratified analysis on several study characteristics. Data Synthesis: Data analyses suggest publication bias and heterogeneity of source data for the ε4 allele (homogeneity P=.2; Begg and Mazumdar, P=.06; and Egger et al, P=.1). The estimated odds ratios for development of dementia in PD are 1.6 for ε4 (95% confidence interval, 1.0-2.5); 1.3 for ε2 (95% confidence interval, 0.73-2.4); and 0.54 for ε3 (95% confidence interval, 0.18-1.6). The odds ratio estimates for ε4 were higher for studies published in 1996 or later (2.3 vs 1.0) and for studies conducted outside North American sites (2.4 vs 1.2). Conclusions: The APOE aε4 allele appears to be associated with a higher prevalence of dementia in PD. Publication bias and heterogeneous source data may, however, confound this conclusion. Confirmatory studies that use standardized and validated diagnostic criteria for dementia in PD are needed.