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CEREBELLAR VOLUME AND DISEASE STAGING IN PARKINSON’S DISEASE: AN ENIGMA-PD STUDY

A novel machine learning algorithm, the ENIGMA cerebellum parcellation protocol ACAPULCO, quantified anterior and posterior cerebellar lobe volumes in PD associated with motor/non- motor symptoms across different stages of the disease.The association between worse cognitive performance and smaller cerebellar volume opens up new insights into the functional reorganization of the cerebellum and its communication with the basal ganglia (2,3). This study highlightsthe importance of incorporating the cerebellum into novel neurobiological models of PD for future clinical trials for treatment approaches directed specific brain regions.

Kerestes et al (1) applied the standardized ENIGMA cerebellum parcellation protocol ACAPULCO to quantify cerebellar lobule volume from 2847 adults with PD and 1212 controls. Less severe disease Hoehn and Yahr stages (HY1) were associated with larger anterior “motor” lobe regions, more severe disease stages (HY3, HY4–5) were associated with lower volumes principally weighted to posterior “non-motor” lobes of the cerebellum. Lobule VIIB showed a nonlinear pattern of lower volume with each HY-increment bilaterally, with the most significant group differences in HY4–5 compared to controls. Total cerebellar volume was significantly lower in PD patients with cognitive decline compared to those cognitively normal, independent of motor severity.

Key Points:

  • Anterior cerebellar lobe morphology is related to two core motor symptoms, i.e., tremor and rigidity.
  • There is a targeted involvement of motor cerebellar pathways during earlier disease stages and of non-motor cerebellar pathways in the later stages of the disease.
  • The initially increased anterior cerebellar lobe volumeis not sustained over time and posterior lobe volume declines as the disease progresses.
  • Τhe question whether cerebellar degeneration is a primary or a secondary phenomenon of cortical and basal ganglia degeneration remains elusive.
  • Variability of clinical confounders, such as the OFF state for the MDS-UPDRS Part 3, variability in medication across sites influenced disease severity measures.

References:

  1. Kerestes R, Laansma MA, Owens-Walton C, Perry A, van Heese EM, Al-Bachari S, Anderson TJ, Assogna F, Aventurato ÍK, van Balkom TD, Berendse HW, van den Berg KRE, Betts R, Brioschi R, Carr J, Cendes F, Clark LR, Dalrymple-Alford JC, Dirkx MF, Druzgal J, Durrant H, Emsley HCA, Garraux G, Haroon HA, Helmich RC, van den Heuvel OA, João RB, Johansson ME, Khachatryan SG, Lochner C, McMillan CT, Melzer TR, Mosley PE, Newman B, Opriessnig P, Parkes LM, Pellicano C, Piras F, Pitcher TL, Poston KL, Rango M, Roos A, Rummel C, Schmidt R, Schwingenschuh P, Silva LS, Smith V, Squarcina L, Stein DJ, Tavadyan Z, Tsai CC, Vecchio D, Vriend C, Wang JJ, Wiest R, Yasuda CL, Young CB, Jahanshad N, Thompson PM, van der Werf YD, Harding IH; ENIGMA-Parkinson's Study. Cerebellar Volume and Disease Staging in Parkinson's Disease: An ENIGMA-PD Study. Mov Disord. 2023 Dec;38(12):2269-2281. doi: 10.1002/mds.29611.
  2. Koziol LF, Budding D, Andreasen N, et al. Consensus paper: the cerebellum’s role in movement and cognition. Cerebellum 2014;13(1): 151–177.
  3. Grasby KL, Jahanshad N, Painter JN, et al. The genetic architecture of the human cerebral cortex. Science 2020;367(6484)

Co-authors:

Yıldız Değirmenci,
Department of Neurology, School of Medicine, Istanbul Health and Technology University

 

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