Structural and Functional Brain Changes in Middle-Aged Type 2 Diabetic Patients: A Cross-Sectional Study

Article type: Research Article

Authors: García-Casares, Natalia^{a; b; *} | Berthier, Marcelo L.^{a; b} | Jorge, Ricardo E.^c | Gonzalez-Alegre, Pedro^d | Gutiérrez Cardo, Antonio^b | Rioja Villodres, José^{a; b} | Acion, Laura^e | Ariza Corbo, María José^{a; b} | Nabrozidis, Alejandro^b | García-Arnés, Juan A.^f | González-Santos, Pedro^{a; b; g}

Affiliations: [a] Department of Medicine, Faculty of Medicine, University of Malaga, Spain | [b] Centro de Investigaciones Médico-Sanitarias (C.I.M.E.S), Malaga, Spain | [c] Department of Psychiatry, Iowa City Veterans Administration Medical Center, The University of Iowa, West Iowa City, IA, USA | [d] Department of Neurology, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA | [e] The Iowa Consortium for Substance Abuse Research and Evaluation, The University of Iowa, Iowa City, IA, USA | [f] Department of Endocrinology, Carlos-Haya Hospital, Malaga, Spain | [g] Department of Internal Medicine, University Hospital Virgen de la Victoria, Malaga, Spain

Correspondence: [*] Correspondence to: Natalia García Casares, Department of Medicine, Faculty of Medicine, University of Malaga, Boulevard Louis Pasteur 32, 29010 Malaga, Spain. Tel.: +34952137354; Fax: +34952131615; E-mail: Nagcasares@uma.es.

Abstract: Background:Type 2 diabetes mellitus (T2DM) is an emerging risk factor for cognitive impairment. Whether this impairment is a direct effect of this metabolic disorder on brain function, a consequence of vascular disease, or both, remains unknown. Structural and functional neuroimaging studies in patients with T2DM could help to elucidate this question. Objective:We designed a cross-sectional study comparing 25 T2DM patients with 25 age- and gender-matched healthy control participants. Clinical information, APOE genotype, lipid and glucose analysis, structural cerebral magnetic resonance imaging including voxel-based morphometry, and F-18 fluorodeoxyglucose positron emission tomography were obtained in all subjects. Methods:Gray matter densities and metabolic differences between groups were analyzed using statistical parametric mapping. In addition to comparing the neuroimaging profiles of both groups, we correlated neuroimaging findings with HbA1c levels, duration of T2DM, and insulin resistance measurement (HOMA-IR) in the diabetic patients group. Results:Patients with T2DM presented reduced gray matter densities and reduced cerebral glucose metabolism in several fronto-temporal brain regions after controlling for various vascular risk factors. Furthermore, within the T2DM group, longer disease duration, and higher HbA1c levels and HOMA-IR were associated with lower gray matter density and reduced cerebral glucose metabolism in fronto-temporal regions. Conclusion:In agreement with previous reports, our findings indicate that T2DM leads to structural and metabolic abnormalities in fronto-temporal areas. Furthermore, they suggest that these abnormalities are not entirely explained by the role of T2DM as a cardiovascular risk factor.

Keywords: cognition, magnetic resonance imaging, neuroimaging, positron emission tomography, type 2 diabetes mellitus

DOI: 10.3233/JAD-131736

Journal: Journal of Alzheimer's Disease, vol. 40, no. 2, pp. 375-386, 2014