To determine whether interactions between the APOE e4 genotype and sex affect cognitive impairment in people with Parkinson’s Disease (PD).

PD patients are at high risk of developing cognitive impairment and dementia.  Male sex has been linked to increased risk for cognitive impairment.  APOE e4 allele increases the risk of cognitive impairment in PD.  However, the interaction between APOE e4 and sex in regard to cognitive impairment in PD has yet to be fully explored.

1753 participants with Parkinson’s Disease underwent a comprehensive battery of cognitive tests.  There were 1176 males and 577 females, with 272 males and 131 females with an APOE e4 allele.  The association between each cognitive test variable, genotype, and genotype by sex interaction was tested using separate linear regressions under a dominant genetic model adjusting for age, disease duration, education, and site. If a significant interaction was found, analyses were repeated separately for males and females. Logistic regression was used to determine whether genotype and/or sex by genotype interactions were associated with cognitive diagnosis.

For most cognitive measures, there was no sex by genotype interaction.  However, there was a significant  APOE e4 by sex interaction for the visuospatial domain (p = 0.02).  Female participants with an e4 allele performed worse on a visuospatial task than those without an e4 allele (p = 0.001), while male performance on this task was unaffected by APOE genotype (p = 0.931). 

Females with at least one APOE e4 allele perform worse on a non-motor visuospatial task than females without an APOE e4 allele.  There was no difference on this task for males with or without APOE e4 allele.  We conclude that the effect of APOE e4 allele may impact visuospatial functioning differently for males and females with PD.