Apathy: An underestimated feature in GBA and LRRK2 non-manifesting mutation carriers

• Published in: Parkinsonism & related disorders 2021-10, Vol.91, p.1-8
• Main Authors: Pachi, Ioanna, Koros, Christos, Simitsi, Athina M., Papadimitriou, Dimitra, Bougea, Anastasia, Prentakis, Andreas, Papagiannakis, Nikolaos, Bozi, Maria, Antonelou, Roubina, Angelopoulou, Efthalia, Beratis, Ion, Stamelou, Maria, Trapali, Xenia Geronicola, Papageorgiou, Sokratis G., Stefanis, Leonidas
• Format: Article
• Language: English
• Subjects: Aged; Apathy; Case-Control Studies; Cross-Sectional Studies; Databases, Factual; Female; Glucosylceramidase - genetics; Heterozygote; Humans; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - genetics; Male; Middle Aged; Mutation; Neuropsychological Tests; Non-manifesting carriers; Parkinson Disease - genetics; Parkinson's disease; Retrospective Studies
• ISSN: 1353-8020; 1873-5126
• DOI: 10.1016/j.parkreldis.2021.08.008

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. 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 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. 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. GBA carriers were 1.5 times more likely to develop features of anxiety compared to LRRK2 carriers (adjusted OR = 1.5, 95% CI = 1.1–2.2, p = 0.015). Other neuropsychiatric symptoms, such as psychotic or depressive manifestations, did not differ between groups. 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. •Apathy could be present in the premotor period of mutation carriers.•GBA non-manifesting carriers had a three-fold risk to develop apathy compared to controls.•Anxiety was more prevalent in GBA asymptomatic carriers, compared to LRRK2 carriers.•The prevalence of psychiatric features did not differ significantly between LRRK2 asymptomatic carriers and healthy controls.•Hallucinations, depression, anxiety and impulsivity did not differ between carriers and controls.