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

Ioanna Pachi; Christos Koros; Athina M Simitsi; Dimitra Papadimitriou; Anastasia Bougea; Andreas Prentakis; Nikolaos Papagiannakis; Maria Bozi; Roubina Antonelou; Efthalia Angelopoulou; Ion Beratis; Maria Stamelou; Xenia Geronicola Trapali; Sokratis G Papageorgiou; Leonidas Stefanis

doi:10.1016/j.parkreldis.2021.08.008

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

Parkinsonism Relat Disord. 2021 Oct:91:1-8. doi: 10.1016/j.parkreldis.2021.08.008. Epub 2021 Aug 18.

Authors

Affiliations

¹ 1st Department of Neurology, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
² Neurology Clinic, Henry Dunan Hospital, Athens, Greece.
³ Nuclear Medicine Unit, Attikon Hospital, Athens, Greece.
⁴ 2nd Department of Neurology, "Attikon" University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
⁵ Parkinson's Disease and Movement Disorders Department, HYGEIA Hospital, Athens, Greece; School of Medicine, European University of Cyprus, Nicosia, Cyprus.
⁶ 1st Department of Neurology, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: lstefanis@bioacademy.gr.

PMID: 34425330
DOI: 10.1016/j.parkreldis.2021.08.008

Abstract

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 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.

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. 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.

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.

Keywords: Apathy; Non-manifesting carriers; Parkinson's disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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
Parkinson Disease / genetics*
Retrospective Studies

Substances

LRRK2 protein, human
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
GBA protein, human
Glucosylceramidase