Objective: The aim was to detect the differences between GBA and LRRK2 mutation carriers without Parkinson’s disease and healthy controls (HC) on neuropsychiatric symptoms.
Background: Higher prevalence of motor and non-motor features, such as mild cognitive decline and autonomic dysfunction, has been observed in non-manifesting mutation carriers compared to HC. Few reports have assessed the neuropsychiatric manifestations in these groups.
Method: This is a cross-sectional retrospective study of non-manifesting GBA and LRRK2 mutation carriers and HC enrolled into Parkinson’s Progression Markers Initiative (PPMI). Data extracted from PPMI database contained: demographics, performance in MoCA scale and MDS-UPDRS scale part 1A including cognitive impairment, hallucinations, depressed and anxious mood, apathy and features of dopamine dysregulation syndrome. All six neuropsychiatric 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: We found that non-manifesting mutation carriers (total N=654, GBA: n=285, LRRK2: n=369) were 2.3 times more likely to present apathy compared to HC, even after adjustment for demographic and clinical factors (adjusted OR=2.3, 95% CI=1.1-5.0, p-value=0.027). The effect was mainly driven by GBA mutation carriers. Anxiety was significantly more prevalent in GBA compared to LRRK2 mutation carriers (adjusted OR=1.5, 95% CI=1.1-2.2, p-value= 0.015). Other neuropsychiatric symptoms, such as psychotic or depressive manifestations, did not differ between groups.
Conclusion: Symptoms of apathy could be present in the premotor period of LRRK2 and, especially, GBA mutation carriers. Longitudinal data, including detailed neuropsychiatric evaluation and neuroimaging, would be essential to confirm and further investigate the neuroanatomical basis of this finding.
To cite this abstract in AMA style:
I. Pachi, C. Koros, A. Simitsi, D. Papadimitriou, A. Bougea, A. Prentakis, N. Papagiannakis, M. Bozi, R. Antonelou, E. Angelopoulou, I. Beratis, M. Stamelou, X. Trapali, S. Papageorgiou, L. Stefanis. Apathy: an underestimated feature in premotor period of GBA and LRRK2 non-manifesting mutation carriers. [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/apathy-an-underestimated-feature-in-premotor-period-of-gba-and-lrrk2-non-manifesting-mutation-carriers/. Accessed June 15, 2025.« Back to MDS Virtual Congress 2021
MDS Abstracts - https://www.mdsabstracts.org/abstract/apathy-an-underestimated-feature-in-premotor-period-of-gba-and-lrrk2-non-manifesting-mutation-carriers/