Anomalous White Matter Structure and the Effect of Age in Down Syndrome Patients

Article type: Research Article

Authors: Fenoll, Raquel^a | Pujol, Jesus^{a; b; *} | Esteba-Castillo, Susanna^c | de Sola, Susana^{d; e} | Ribas-Vidal, Núria^c | García-Alba, Javier^f | Sánchez-Benavides, Gonzalo^d | Martínez-Vilavella, Gerard^a | Deus, Joan^{a; g} | Dierssen, Mara^{e; h; 1} | Novell-Alsina, Ramón^{c; 1} | de la Torre, Rafael^{d; i; j; 1}

Affiliations: [a] MRI Research Unit, Department of Radiology, Hospital del Mar, Barcelona, Spain | [b] Centro Investigación Biomédica en Red de Salud Mental, CIBERSAM G21, Barcelona, Spain | [c] Specialized Department in Mental Health and Intellectual Disability, Institut d’Assistència Sanitària (IAS), Girona, Catalonia, Spain | [d] Integrative Pharmacology and Neuroscience Systems Research Group, Hospital del Mar Medical Research Institute, Barcelona, Spain | [e] Cellular & Systems Neurobiology, Centre for Genomic Regulation (CRG), Barcelona, Spain | [f] Department of Adults with Down Syndrome, Hospital Universitario de La Princesa, Madrid, Spain | [g] Department of Clinical and Health Psychology, Autonomous University of Barcelona, Spain | [h] Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain | [i] Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Madrid, Spain | [j] Department de Ciències Experimentals i de la Salut Universitat Pompeu Fabra (CEXS-UPF), Barcelona, Spain

Correspondence: [*] Correspondence to: Dr. Jesus Pujol, MD, MRI Department, Hospital del Mar, Passeig Marítim 25-29, 08003, Barcelona, Spain. Tel.: +34932212180; Fax: +34932212181; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Background: Neural tissue alterations in Down syndrome are fully expressed at relatively late developmental stages. In addition, there is an early presence of neurodegenerative changes in the late life stages. Objective: The aims of this study were both to characterize white matter abnormalities in the brain of adult Down syndrome patients using diffusion tensor imaging (DTI) and to investigate whether degenerative alterations in white matter structure are detectable before dementia is clinically evident. Methods: Forty-five adult non-demented Down syndrome patients showing a wide age range (18–52 years) and a matched 45-subject control group were assessed. DTI fractional anisotropy (FA) brain maps were generated and selected cognitive tests were administered. Results: Compared with healthy controls, non-demented Down syndrome patients showed lower DTI FA in white matter involving the major pathways, but with more severe alterations in the frontal-subcortical circuits. White matter FA decreased with age at a similar rate in both DS and control groups. Conclusions: Our results contribute to characterizing the expression of white matter structural alterations in adult Down syndrome. However, an accelerated aging effect was not demonstrated, which may suggest that the FA measurements used are not sufficiently sensitive or, alternatively, age-related white matter neurodegeneration is not obvious prior to overt clinical dementia.

Keywords: Accelerated aging, diffusion tensor imaging, magnetic resonance imaging, neurodegeneration

DOI: 10.3233/JAD-161112

Journal: Journal of Alzheimer's Disease, vol. 57, no. 1, pp. 61-70, 2017