Cortical and subcortical morphological alterations in <i>de novo GBA</i>-related Parkinson's disease.

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BackgroundThis study aimed to investigate cortical and subcortical changes in GBA-related Parkinson's disease (GBA-PD) patients and evaluate the ability of these structural changes to identify patients with GBA-PD.MethodsT1-weighted magnetic resonance imaging images were obtained for 86 participants, including 19 GBA-PD, 42 idiopathic PD (iPD) cases, and 25 healthy controls (HCs). Cortical thickness, cortical volume, and subcortical volume (including amygdala volume) were calculated to identify cortical and subcortical morphological alterations and correlated with cognitive function. To reduce overfitting, classification was performed using least absolute shrinkage and selection operator (LASSO)-penalized logistic regression with nested stratified 5-fold cross-validation.ResultsCompared with iPD patients, GBA-PD patients had reduced cortical thickness in the left superior temporal sulcus (STS.L) and left superior occipital gyrus (SOG.L) as well as reduced cortical volume in the SOG.L and right amygdala subregion, including the basal nucleus, accessory basal nucleus, cortico-amygdaloid transition area, and paralaminar nucleus. Cortical thickness and cortical volume in the SOG.L, right basal nucleus, and right paralaminar nucleus were negatively correlated with memory and visuospatial function, respectively. After internal cross-validation, the exploratory LASSO-based model combining age, sex, and significant cortical and subcortical morphometric features showed moderate discrimination between GBA-PD and iPD, with an area under the curve of 0.821, sensitivity of 56.3%, and specificity of 88.1%.ConclusionGBA-PD patients showed distinct patterns of cortical thickness and volume thinning, as well as amygdala subregional atrophy. These cortical and subcortical changes may contribute to future exploratory phenotypic characterization or patient stratification, but validation in larger independent cohorts is required.

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