Following the Spreading of Brain Structural Changes in Alzheimer’s Disease: A Longitudinal, Multimodal MRI Study

Article type: Research Article

Authors: Weiler, Marina^{a; f} | Agosta, Federica^a | Canu, Elisa^a | Copetti, Massimiliano^e | Magnani, Giuseppe^b | Marcone, Alessandra^c | Pagani, Elisabetta^a | Balthazar, Marcio Luiz Figueredo^f | Comi, Giancarlo^b | Falini, Andrea^d | Filippi, Massimo^{a; b; *}

Affiliations: [a] Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy | [b] Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy | [c] Department of Clinical Neurosciences, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy | [d] Department of Neuroradiology and CERMAC, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy | [e] Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy | [f] Laboratory of Neuroimaging, University of Campinas, Campinas, Brazil

Correspondence: [*] Correspondence to: Prof. Massimo Filippi, Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-SaluteSan Raffaele University, Via Olgettina, 60, 20132 Milan, Italy. Tel.: +39 02 26433033; Fax: +39 02 26433031; filippi.massimo@hsr.it

Abstract: Background: Longitudinal MRI studies in Alzheimer’s disease (AD) are one of the most reliable way to track brain changes along the course of the disease. Objective: To investigate the evolution of grey matter (GM) atrophy and white matter (WM) damage in AD patients, and to assess the relationships of MRI changes with baseline clinical and cognitive variables and their evolution over time. Methods: Clinical, neuropsychological, and MRI assessments (T1-weighted and diffusion tensor [DT]-MRI) were obtained from 14 patients with AD at baseline and after a 16 ± 3 month period. Lumbar puncture was obtained at study entry. At baseline, AD patients were compared to 37 controls. GM atrophy progression was assessed with tensor-based morphometry and GM volumes of interest, and WM damage progression using tract-based spatial statistics and tractography. Results: At baseline, patients showed cortical atrophy in the medial temporal and parietal regions and a widespread pattern of WM damage involving the corpus callosum, cingulum, and temporo-occipital, parietal, and frontal WM tracts. During follow up, AD patients showed total GM atrophy, while total WM volume did not change. GM tissue loss was found in frontal, temporal, and parietal regions. In addition, AD patients showed a progression of WM microstructural damage to the corpus callosum, cingulum, fronto-parietal and temporo-occipital connections bilaterally. Patients with higher baseline cerebrospinal fluid total tau showed greater WM integrity loss at follow up. GM and WM changes over time did not correlate with each other nor with cognitive evolution. Conclusion: In AD, GM atrophy and WM tract damage are likely to progress, at least partially, independently. This study suggests that a multimodal imaging approach, which includes both T1-weighted and DT MR imaging, may provide additional markers to monitor disease progression.

Keywords: Alzheimer’s disease, grey matter atrophy, longitudinal MRI, progression, tau pathology, white matter tract damage

DOI: 10.3233/JAD-150196

Journal: Journal of Alzheimer's Disease, vol. 47, no. 4, pp. 995-1007, 2015