Introduction: Higher prevalence of motor and non-motor features has been observed in non-manifesting mutation carriers of Parkinson s Disease (PD) compared to Healthy Controls (HC). The aim was to detect the differences between GBA and LRRK2 mutation carriers without PD and HC on neuropsychiatric symptoms.
Methods: This is a cross-sectional retrospective study of non-manifesting GBA and LRRK2 mutation carriers and HC enrolled into Parkinsons Progression Markers Initiative (PPMI). Data extracted from the PPMI database contained: demographics and performance in MoCA scale and MDS-UPDRS scale part 1A (neuropsychiatric symptoms). All six features were treated as both continuous (MDS-UPDRS individual scores) and categorical variables (MDS-UPDRS individual score>0 and MDS-UPDRS individual score=0). Logistic regression analyses were applied to evaluate the association between mutation carrying status and neuropsychiatric symptoms.
Results: In this study, the neuropsychiatric evaluation was performed in 285 GBA non-manifesting carriers, 369 LRRK2 non-manifesting carriers and 195 HC. We found that GBA non-manifesting mutation carriers were 2.6 times more likely to present apathy compared to HC, even after adjustment for covariates (adjusted OR=2.6, 95% CI=1.1-6.3, p=0.031). The higher percentage of apathy for LRRK2 carriers compared to HC was marginally non-significant. Other neuropsychiatric symptoms, such as psychotic or depressive manifestations, did not differ between groups.
Conclusion: Symptoms of apathy could be present in the prediagnostic period of non-manifesting mutation carriers, especially, GBA. Longitudinal data, including detailed neuropsychiatric evaluation and neuroimaging, would be essential to further investigate the pathophysiological basis of this finding
α-Synuclein Levels in Blood Plasma from LRRK2 Mutation Carriers
