Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Oct 14:2018:9497147.
doi: 10.1155/2018/9497147. eCollection 2018.

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

Suisui Pang  1 , Jia Li  1 , Yingyu Zhang  1 , Jiajun Chen  1
Affiliations
Review

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

Suisui Pang et al. Parkinsons Dis. .

Abstract

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. ε3/3, ε2+/ε4+ vs. ε3/3, and ε4+ vs. ε4-. The risk factors for PDD may include the genotypes ε3/4 (OR 1.47, 95% CI 1.14-1.89) and ε4/4 (OR 2.93, 95% CI 1.20-7.14). In patients with PDD, there was no significant difference in the distribution of ε2+ vs. ε3/3 (OR 1.35, 95% CI 0.97-1.87, P=0.07). The risk of PDD was 1.61 times greater in ε4+ compared with ε3/3 (OR 1.61, 95% CI 1.24-2.08, P=0.0003). As the results indicated that ε2+ did not play a role as a risk factor or a protective factor, we divided the population into ε4+ and ε4- for the meta-analysis and found that, among patients with Parkinson's disease, the dementia risk of those with ε4+ was 1.72 times greater than that of those with ε4- (OR 1.72, 95% CI 1.41-2.10, P < 0.00001). Subgroup analysis in accordance with different geographical regions revealed that ε4+ was a risk factor for PDD in people from all regions.

Conclusions: Among the APOE genotypes, ε2+ is neither a risk factor nor a protective factor for PDD, while ε4+ 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, ε3/4 and ε4/4 may be risk factors for PDD; however, further studies with large sample sizes are needed to verify this.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Flow chart of the study retrieval process.
Figure 2
Figure 2
Risk of Parkinson's disease dementia in those with the five APOE genotypes compared with the ε3/3 genotype (assessed in 10 studies).
Figure 3
Figure 3
Forest plot for the risk of Parkinson's disease dementia onset in ε2+ patients assessed in 10 studies.
Figure 4
Figure 4
Forest plot for the risk of Parkinson's disease dementia onset in ε4+ patients assessed in 10 studies.
Figure 5
Figure 5
Forest plot for the risk of Parkinson's disease dementia onset in ε4+ versus ε4− patients assessed in 17 studies.
Figure 6
Figure 6
Forest plot for the influence of regional distribution on Parkinson's disease dementia onset risk of ε2+ patients.
Figure 7
Figure 7
Forest plot for the influence of regional distribution on Parkinson's disease dementia onset risk of ε4+ patients.
Figure 8
Figure 8
Forest plot for the influence of geographical distribution on Parkinson's disease dementia onset risk of ε4+ patients compared with ε4− patients.
Figure 9
Figure 9
Funnel plots of ε2+ vs. ε3/3, ε4+ vs. ε3/3, and ε4+ vs. ε4−.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Aarsland D., Zaccai J., Brayne C. A systematic review of prevalence studies of dementia in parkinson’s disease. Movement Disorders. 2005;20(10):1255–1263. doi: 10.1002/mds.20527. - DOI - PubMed
    1. Levy G., Tang M. X., Louis E. D., et al. The association of incident dementia with mortality in PD. Neurology. 2002;59(11):1708–1713. doi: 10.1212/01.wnl.0000036610.36834.e0. - DOI - PubMed
    1. Emre M., Aarsland D., Brown R., et al. Clinical diagnostic criteria for dementia associated with parkinson’s disease. Movement Disorders. 2007;22(12):1689–1707. doi: 10.1002/mds.21507. - DOI - PubMed
    1. Irwin D. J., White M. T., Toledo J. B., et al. Neuropathologic substrates of parkinson disease dementia. Annals of Neurology. 2012;72(4):587–598. doi: 10.1002/ana.23659. - DOI - PMC - PubMed
    1. Del Tredici K., Braak H. Dysfunction of locus coeruleus-norepinephrine system and related circuitry in parkinson’s disease-related dementia. Journal of Neurology, Neurosurgery and Psychiatry. 2013;84(7):774–783. doi: 10.1136/jnnp-2011-301817. - DOI - PubMed