Brain Atrophy Patterns Similar in Parkinson Disease Regardless of Brain- or Body-First Marker Changes

Thilo V. Eimeren, MD

Recently published research evaluating de novo patients with Parkinson disease (PD) showed no diverging brain atrophy pattern based on whether patients had a brain-first spreading subtype of α-synuclein or body-first subtype. This study failed to prove a previous hypothesis that brain-first subtypes would be associated with a more asymmetric cerebral and nigrostriatal pathology than body-first subtypes.¹

Senior investigator Thilo V. Eimeren, MD, professor, Multimodal Brain Imaging, University of Cologne, and colleagues, concluded that, "At the least, our findings indicate that the proposed earlier involvement of the central nervous system (in particular the amygdala) in probable brain-first PD is not reflected in a greater volume reduction. However, the hypothesis is very interesting for the investigation of the heterogeneity of PD and should be further investigated."

Using a cohort of 255 patients with PD and 110 healthy controls (HC), investigators tested whether brain-first PD proposed markers such as higher dopamine transporter (DaT) asymmetry, and absence of rapid eye movement sleep behavior disorder (RBD) are associated with a greater or more asymmetric reduction in gray matter volume (GMV) in comparison with body-first PD. Structural magnetic resonance images were preprocessed, and GMVs and their hemispherical asymmetry were obtained for each of the neuropathologically defined Braak stages.

Between HCs and patients with PD, significantly smaller GMV was observed in those with the disease for brain regions representing stages 1 + 2 (F[1, 364] = 159.36; P <.001); stage 3 (F(1, 364) = 5.48; P = .02); and stage 4 (F[1, 364] = 54.81; P <.001). No significant differences were observed for brain regions representing stages 5 + 6, nor any significant differences in the left amygdala; however the right amygdala GMV was significantly smaller in the PD group (F[1, 364] = 5.44; P = .02).

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Between brain-first and body-first patients with PD, investigators found no significant relations between increased putamen asymmetry index (AI), a putative brain-first subtype, with the more affected hemisphere (MAH)_GMV, less-affected hemisphere (LAH)_GMV, or GMV AI in any Braak stage. After applying the Bonferroni-adjusted threshold of P <.003, no significant group differences were observed between RBD-positive and RBD-negative patients in the MAH_GMV, LAH_GMV, or GMV AI in any Braak stage.

In terms of asymmetry in patients with PD, there was a significantly smaller GMV in the left hemisphere compared with the right hemisphere in stages 1 + 2 (F[1, 506] = 29.16; P = .001), which was independent of the MAH_DaT (F[1, 506] = 0.07; P = .797). There was no significant difference between the hemispheres in stage 3 (F[1, 506] = 0.74; P = .39), stage 4 (F[1, 506] = 2.24; P = .136) or stages 5 + 6 (F[1, 506] = 0.19; P = .661). Notably, across any Braak stage, there was no significant difference in MAHGMV or LAHGMV (F[3, 2032] = 0.58; P = 0.9).

GMV AI significantly differed across Braak stages (H [3] = 158.46; P <.001), with significant differences observed of stages 1 + 2 from that of stage 3 (difference = 169.42), stage 4 (difference = 194.17), and stages 5 + 6 (difference = 326.38). GMV AI of stage 3 did not significantly differ from stage 4 (difference = 25.05) but did significantly differ from stages 5 + 6 (difference = 131.91). Overall, the critical difference (α = 0.05) was 68.83.

REFERENCE
1. Banwinkler M, Dzialas V, Hoenig MC, van Eimeren T. Gray matter volume loss in proposed brain-first and body-first Parkinson’s disease subtypes. Mov Disord. Published online August 9, 2022. doi:10.1002/mds.29172