Objective: To assess differences in cognitive domains  between patients with Parkinson’s disease with the LRRK2 and GBA risk mutations

Background: Most patients with PD show some cognitive decline specifically in  anterior cognitive circuits characterized by working memory, processing speed and attention. Language, memory and visuospatial abilities reflect posterior deficits. The MDS task force guidelines for the diagnosis of mild cognitive impairment state that impairment should be present on at least two tests, within a single cognitive domain or across different domains. Differences in domain involvment may indicate dissimilar pathological propagation that may affect disease progression

Method: 195 recently diagnosed patients with PD (<3years from diagnosis) participated in this study. All patients underwent genetic phenotyping. Cognitive evaluation included multiple validated neurospychological tests in each cognitive domain; executive function (e.g., SDMT, TMT, Stroop), Memory (e.g., HVLT, MOCA, digit span, verbal fluency); visual spatial (e.g., hooper, clock drawing), and language (e.g., semantic verbal fluency and MOCA). Test scores were compared to  culturally appropriate norms.  Performance lower than 1 standard deviation (SDs) below age, education and gender norms was considered abnormal

Results: 41 PD-LRRK2 (mean age: 63.6±11.1yrs, 61%M), 84 PD-GBA (64.9±9.7yrs, 64%M),  and 70 idiopathic PD (65.3±11.5yrs, 69%M) completed the evaluation. Global cognitive function, as measured by the MOCA, was highest in PD-LRRK2 (25.5±3.46) and lowest for the PD-GBA (23.8±3.6). PD-LRRK2 showed normal or mild executive function impairment that did not meet the criteria for PD MCI. PD-GBA showed significant impairment in all cognitive domains and specifically in posterior cortical domains such as language, visuospatial and memory. Idiopathic PD patients had mostly executive function deficits but met the criteria for PD MCI with impairments in the SDMT, TMT and HVLT

Conclusion: Our study shows that cognitive impairment is widely distributed even in early stage PD patients and is asssociated with genetic status. iPD patients and to a lesser degree LRRK2 patients have mostly frontal striatal deficits while PD-GBA, have multiple domain MCI with impairment on all cognitive domains and especially posterior cortical and temporal domains. These findings may help target therapeutic options

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MDS Abstracts - https://www.mdsabstracts.org/abstract/genetic-contribution-to-domain-specific-cognitive-decline/