Absence of the apolipoprotein E ε4 allele is associated with working memory impairment in Parkinson's disease

The apolipoprotein E (APOE) ε4 allele has been associated with an increased risk of Alzheimer's disease (AD) and weaker episodic memory among elderly. Although this APOE allele has been linked to earlier onset of Parkinson's disease (PD), an association with dementia in PD has been only inconsistently demonstrated. Given the heterogeneity of cognitive impairment patterns in PD, this study sought to determine whether an association exists between APOE genotype and specific cognitive deficits in PD. The neuropsychological test performance of 42 PD patients without an ε4 allele (PD-Non4) and of 20 with at least one ε4 allele (PD-ε4) was compared to that of 146 elderly control subjects (NC). The PD groups were comparable in overall severity of cognitive impairment and disease duration, but the PD-ε4 group was younger, had an earlier disease onset, and contained a higher proportion of persons with dementia. Both PD groups showed wide-ranging cognitive impairments relative to NC. Once age differences between groups were controlled for, the PD groups generally did not differ from each other in cognitive performance. However, only the PD-Non4 group demonstrated working memory/attention impairments (digit span, visual span, Trailmaking test) relative to the NC group. Results suggest that the APOE genotype may influence the cognitive phenotype of PD, and specifically that absence of the ε4 allele is associated with working memory impairment. Additionally, results are consistent with prior findings showing an association between the ε4 allele and earlier onset of PD and presence of dementia.