Cerebellar White Matter Disruption in Alzheimer’s Disease Patients: A Diffusion Tensor Imaging Study

Article type: Research Article

Authors: Toniolo, Sofia^{a; b} | Serra, Laura^a | Olivito, Giusy^{c; d} | Caltagirone, Carlo^{b; d} | Mercuri, Nicola Biagio^b | Marra, Camillo^e | Cercignani, Mara^f | Bozzali, Marco^{a; f; *}

Affiliations: [a] Neuroimaging Laboratory, Fondazione Santa Lucia, IRCCS, Rome, Italy | [b] Department of Neuroscience, University of Rome ‘Tor Vergata’, Rome, Italy | [c] Department of Psychology, Sapienza University of Rome, Rome, Italy | [d] Ataxia Research Laboratory-Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy | [e] Department of Clinical and Behavioural Neurology, Fondazione Santa Lucia, IRCCS, Rome, Italy | [f] Institute of Neurology, Catholic University, Rome, Italy | [g] Department of Neuroscience, Brighton and Sussex Medical School, University of Sussex, Falmer, East Sussex, UK

Correspondence: [*] Correspondence to: Prof. Marco Bozzali, Department of Neuroscience, Brighton and Sussex Medical School, University of Sussex, Brighton, East Sussex, BN1 9RH, UK. Tel.: +44 0 1273 873509; Fax: +44 0 1273 876721; E-mail: [email protected].

Abstract: The cognitive role of the cerebellum has recently gained much attention, and its pivotal role in Alzheimer’s disease (AD) has now been widely recognized. Diffusion tensor imaging (DTI) has been used to evaluate the disruption of the microstructural milieu in AD, and though several white matter (WM) tracts such as corpus callosum, inferior and superior longitudinal fasciculus, cingulum, fornix, and uncinate fasciculus have been evaluated in AD, data on cerebellar WM tracts are currently lacking. We performed a tractography-based DTI reconstruction of the middle cerebellar peduncle (MCP), and the left and right superior cerebellar peduncles separately (SCPL and SCPR) and addressed the differences in fractional anisotropy (FA), axial diffusivity (Dax), radial diffusivity (RD), and mean diffusivity (MD) in the three tracts between 50 patients with AD and 25 healthy subjects. We found that AD patients showed a lower FA and a higher RD compared to healthy subjects in MCP, SCPL, and SCPR. Moreover, higher MD was found in SCPR and SCPL and higher Dax in SCPL. This result is important as it challenges the traditional view that WM bundles in the cerebellum are unaffected in AD and might identify new targets for therapeutic interventions.

Keywords: Alzheimer’s disease, cerebellum, diffusion tensor imaging, probabilistic tractography, white matter

DOI: 10.3233/JAD-191125

Journal: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 615-624, 2020