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Published on: December 14, 2017
Mild cognitive impairment among LRRK2 and GBA1 patients with Parkinson's disease
Avner Thaler1, Vered Livne2, Einat Rubinstein3
1Faculty of Medicine, Tel-Aviv University, Israel; Movement Disorders Unit, Neurological Institute, Tel-Aviv Medical Center, Israel; Laboratory of Early Markers of Neurodegeneration, Neurological Institute, Tel-Aviv Medical Center, Israel; Sagol School of Neuroscience, Tel-Aviv University, Israel.
Background:
Mild cognitive impairment (MCI) is common in Parkinson's disease (PD). We aimed to assess the incidence of MCI among patients with PD, carriers of mutations in LRRK2 and GBA1 genes, based on the movement disorder society (MDS) criteria for the diagnosis of MCI in early-stage PD.
Methods:
Patients with PD were included if they scored ≤2 on the Hoehn and Yahr and ≤6 years since motor symptom onset. A group of age and gender matched healthy adults served as controls. A neuropsychological cognitive battery was used covering five cognitive domains (executive functions, working memory, memory, visuospatial and language). MCI was explored while applying two methods (level I and II). Frequency of MCI was assessed in comparison between groups.
Results:
70 patients with idiopathic PD (iPD) (68 % males), 42 patients with LRRK2-PD (61 % males), 83 patients with GBA1-PD (63 % males) and 132 age and gender matched controls (61 % males), participated in this study. PD groups were similar in clinical characteristics. Level I criteria were positive in 57.5 % of iPD, 43 % of LRRK2-PD and 63.4 % of the GBA1-PD (p = 0.071). Level II criteria was met by 39 % of iPD, 14 % LRRK2-PD and 41 % of GBA1-PD (p < 0.001), when using a 2 standard-deviation (SD) threshold. GBA1-PD and iPD showed impairments on multiple domains even in the more conservative 2 SD, reflecting MCI.
Conclusions:
The majority of our PD cohort was classified as MCI when assessed with strict criteria. GBA1-PD and iPD showed a more widespread pattern of MCI compared with LRRK2-PD.
Insights
Mild cognitive impairment (MCI) is prevalent in Parkinson's disease (PD). GBA1-PD and idiopathic PD show more widespread MCI than LRRK2-PD, even with strict diagnostic criteria.
Area of Science:
- Neuroscience
- Genetics
- Neurology
Background:
- Mild cognitive impairment (MCI) is a frequent comorbidity in Parkinson's disease (PD).
- Genetic mutations, particularly in LRRK2 and GBA1 genes, are associated with PD.
- Understanding MCI incidence in genetically defined PD subtypes is crucial for early diagnosis and management.
Purpose of the Study:
- To determine the incidence of MCI in early-stage Parkinson's disease (PD) patients.
- To compare MCI prevalence between idiopathic PD (iPD), LRRK2-mutation carriers, and GBA1-mutation carriers.
- To apply Movement Disorder Society (MDS) criteria for MCI diagnosis in distinct PD genetic groups.
Main Methods:
- Inclusion criteria for PD patients: Hoehn and Yahr score ≤2 and ≤6 years since motor symptom onset.
- Cognitive assessment using a neuropsychological battery across five domains: executive functions, working memory, memory, visuospatial, and language.
- MCI evaluation using two methods (Level I and II) and comparison of MCI frequency between PD groups and healthy controls.
Main Results:
- The study included 70 iPD, 42 LRRK2-PD, 83 GBA1-PD patients, and 132 controls.
- Level II criteria (2 SD threshold) revealed MCI in 39% of iPD, 14% of LRRK2-PD, and 41% of GBA1-PD (p < 0.001).
- GBA1-PD and iPD groups exhibited impairments across multiple cognitive domains, indicative of MCI, even under conservative criteria.
Conclusions:
- A majority of the Parkinson's disease cohort met MCI criteria when assessed rigorously.
- GBA1-PD and idiopathic PD demonstrated a broader pattern of cognitive impairment compared to LRRK2-PD.
- These findings highlight the differential impact of genetic mutations on cognitive decline in PD.
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