Mild cognitive impairment among LRRK2 and GBA1 patients with Parkinson's disease

Abstract

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.

Keywords: GBA1; LRRK2; MCI; Parkinson's disease.