Objective: This study aimed to explore the interplay between Apolipoprotein E (ApoE) ε4 allele, brain metabolism, and cognition in non-demented Parkinson’s disease (PD) patients.

Background: The potential contribution of ApoE ε4 allele in PD-related cognitive impairment has been suggested, but the findings have been inconsistent and the underlying mechanisms remain unclear.

Method: We enrolled 158 ApoE ε4–positive PD patients, 36 ApoE ε4–negative PD patients, and 38 healthy individuals who underwent ¹⁸F-FDG PET, ¹⁸F-FP-CIT PET, and brain MRI. Motor symptoms and cognitive function were assessed in PD patients. Partial correlation and mediation analyses were used to investigate the association between the presence of ApoE ε4 allele, altered brain metabolism in related brain regions, cognitive scores, and putaminal dopamine transporter uptake (DAT) availability.

Results: While motor symptoms were comparable between ApoE ε4–positive and negative PD patients, the ApoE ε4–positive group exhibited poorer performance in language and memory domains, as well as lower MMSE and MoCA total scores compared to the ApoE ε4–negative group. PD-related patterns (PDRP) expressions represented by PDRP scores were also significantly more prominent in the ApoE ε4–positive group than the ApoE ε4–negative group. When the metabolic changes of the two groups were directly compared, the ApoE ε4–positive group exhibited lower metabolism in the inferior parietal, lateral temporal, lateral occipital, and middle frontal cortices than the ApoE ε4–negative group. Mediation analyses revealed that hypometabolism of such brain regions mediated the association between ApoE ε4 allele and memory composite scores. The partial correlation between ApoE ε4-related hypometabolism and putaminal DAT specific binding ratio (SBR) appeared stronger in the ApoE ε4-positive group than in the negative group.

Conclusion: ApoE ε4 allele is associated with more prominent PDRP expression, and its association with memory dysfunction is mediated by altered brain metabolism in related brain regions.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/effect-of-apoe-%ce%b54-allele-on-brain-metabolism-and-cognition-in-non-demented-parkinsons-disease/