Brain Structure Deviations in Patients with Parkinson Disease without Dementia Using Normative Modeling

Cortical alterations in Parkinson disease (PD) without dementia remain inconsistent. This study aimed to determine the cortical alterations of PD without dementia and the relationships between cortical alterations and both motor and nonmotor symptoms.

Individualized centile scores for brain structure in 225 patients with PD without dementia were derived from life span brain charts from the Lifespan Brain Chart Consortium and adjusted using a local sample of 451 healthy controls (HC). Compared with the reference (centile score: 0.5), the patterns of structural deviation in patients with PD particularly focused on the cortex. Correlation analysis was performed between centile scores of cortical thickness and motor and nonmotor symptoms.

Compared with normative reference values, 15 of the 34 cortical regions (44.11%) showed negative deviations (Cohen d = -0.15 to -0.39), 3 regions exhibited positive deviations (Cohen d = 0.15 to 0.19), and 16 regions displayed no deviations in patients with PD. The inferior temporal cortex had the highest prevalence of extreme negative deviations (12.00%) and the largest effective size in deviations (Cohen d = -0.39). Independent of the effects of sex or age of onset, patients with PD showed negative deviations in cortical and subcortical gray matter, positive deviations in CSF volume (P < .05), and no deviations in white matter volume (WMV) (P > .05). Cortical thickness was associated with the severity of gait freezing severity (r = -0.18, P = .02) but not with cognitive function (r = -0.05, P > .05), adjusted for age, sex, and Hoehn and Yahr stage.

Cortical changes in PD without dementia are highly heterogeneous, with nearly half of the cortical regions showing negative deviations while the rest exhibit preservation. Global structural alterations include negative deviations in gray matter, positive deviations in CSF, and no deviation in WMV. Thinner cortical thickness may reflect more severe gait freezing.