Understanding the pattern of cognitive decline in GBA1-related Parkinson's Disease: a longitudinal multi-cohort study
Abstract
ObjectivePeople with Parkinsons disease (PD) who carry a pathogenic GBA1 variant (PDGBA1) are at higher risk of cognitive impairment than those without the variant (PDGBA1_wildtype). To date, little is known about the pattern and evolution of cognitive decline in PDGBA1. This multi-center study characterized the cognitive profile of PDGBA, focusing on the longitudinal trajectories and the group-specific onset times among cognitive functions, as well as their clinical relevance.
MethodsIn this longitudinal multicohort-study (PPMI, ABC-PD, Luxembourg Parkinsons Study), comprehensive neuropsychological assessments were standardized across 548 healthy controls (follow-up-years=2.84{+/-}4.33), 906 PDGBA1_wildtype (follow-up-years=4.29{+/-}4.16), and 210 PDGBA1 (follow-up-years=4.09{+/-}3.35). We evaluated performance across age and disease duration using regression (generalized) linear mixed models within each cognitive domain. Time-to-first-event models, assessing risks of clinically relevant performance impairment (test-score z[≤]-1.5, MoCA<26), and an expanding-time-window approach identified the course of cognitive impairment. Additionally, correlations between cognitive functions were calculated.
ResultsAt baseline, PDGBA1 showed lower performance in attention (processing speed) and memory (verbal learning) than PDGBA1_wildtype, but more widespread probability of performance impairment. Over time, attention, visuoperception, memory, and semantic fluency performance declined…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
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