Association of Cortical Gyrification With Imaging and Serum Biomarkers in Patients With Parkinson Disease

Abstract

Background and objectives: Pathologic progression across the cortex is a key feature of Parkinson disease (PD). Cortical gyrification is a morphologic feature of human cerebral cortex that is tightly linked to the integrity of underlying axonal connectivity. Monitoring cortical gyrification reductions may provide a sensitive marker of progression through structural connectivity, preceding the progressive stages of PD pathology. We aimed to examine the progressive cortical gyrification reductions and their associations with overlying cortical thickness, white matter (WM) integrity, striatum dopamine availability, serum neurofilament light (NfL) chain, and CSF α-synuclein levels in PD.

Methods: This study included a longitudinal dataset with baseline (T0), 1-year (T1), and 4-year (T4) follow-ups and 2 cross-sectional datasets. Local gyrification index (LGI) was computed from T1-weighted MRI data to measure cortical gyrification. Fractional anisotropy (FA) was computed from diffusion-weighted MRI data to measure WM integrity. Striatal binding ratio (SBR) was measured from ¹²³Ioflupane SPECT scans. Serum NfL and CSF α-synuclein levels were also measured.

Results: The longitudinal dataset included 113 patients with de novo PD and 55 healthy controls (HCs). The cross-sectional datasets included 116 patients with relatively more advanced PD and 85 HCs. Compared with HCs, patients with de novo PD showed accelerated LGI and FA reductions over 1-year period and a further decline at 4-year follow-up. Across the 3 time points, the LGI paralleled and correlated with FA (p = 0.002 at T0, p = 0.0214 at T1, and p = 0.0037 at T4) and SBR (p = 0.0095 at T0, p = 0.0035 at T1, and p = 0.0096 at T4) but not with overlying cortical thickness in patients with PD. Both LGI and FA correlated with serum NfL level (LGI: p < 0.0001 at T0, p = 0.0043 at T1; FA: p < 0.0001 at T0, p = 0.0001 at T1) but not with CSF α-synuclein level in patients with PD. In the 2 cross-sectional datasets, we revealed similar patterns of LGI and FA reductions and associations between LGI and FA in patients with more advanced PD.

Discussion: We demonstrated progressive reductions in cortical gyrification that were robustly associated with WM microstructure, striatum dopamine availability, and serum NfL level in PD. Our findings may contribute biomarkers for PD progression and potential pathways for early interventions of PD.