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Purpose   To clarify the relationship between certain genotypes or alleles of the  APOE  gene and the onset risk of Parkinson's disease dementia (PDD).Methods   The PubMed, Cochrane, Embase, CBM, CNKI, and Wanfang databases were searched to identify all case-control studies and cohort studies published before October 30, 2017, that investigated the association between the  APOE  gene and the onset of PDD. Manual information retrieval was also performed. All studies that met the quality requirements were included in a meta-analysis performed using RevMan 5.3 software.Results   The meta-analysis included 17 studies, with a total of 820 patients in the PDD group and 1,922 in the non-PDD group. The influence of the  APOE  gene on PDD onset was analyzed from three aspects: five genotypes vs.  ε 3/3,  ε 2+/ ε 4+ vs.  ε 3/3, and  ε 4+ vs.  ε 4−. The risk factors for PDD may include the genotypes  ε 3/4 (OR 1.47, 95% CI 1.14–1.89) and  ε 4/4 (OR 2.93, 95% CI 1.20–7.14). In patients with PDD, there was no significant difference in the distribution of  ε 2+ vs.  ε 3/3 (OR 1.35, 95% CI 0.97–1.87,  P =0.07). The risk of PDD was 1.61 times greater in  ε 4+ compared with  ε 3/3 (OR 1.61, 95% CI 1.24–2.08,  P =0.0003). As the results indicated that  ε 2+ did not play a role as a risk factor or a protective factor, we divided the population into  ε 4+ and  ε 4− for the meta-analysis and found that, among patients with Parkinson's disease, the dementia risk of those with  ε 4+ was 1.72 times greater than that of those with  ε 4− (OR 1.72, 95% CI 1.41–2.10,  P  < 0.00001). Subgroup analysis in accordance with different geographical regions revealed that  ε 4+ was a risk factor for PDD in people from all regions.Conclusions   Among the  APOE  genotypes,  ε 2+ is neither a risk factor nor a protective factor for PDD, while  ε 4+ is a risk factor for PDD. The present results are applicable to Asian, European, and American patients with Parkinson's disease. Regarding the single  APOE  genotypes,  ε 3/4 and  ε 4/4 may be risk factors for PDD; however, further studies with large sample sizes are needed to verify this.

Meta-Analysis of the Relationship between the APOE Gene and the Onset of Parkinson’s Disease Dementia