Cognitive Dysfunctions in Middle-Aged Type 2 Diabetic Patients and Neuroimaging Correlations: A Cross-Sectional Study

Article type: Research Article

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

Affiliations: [a] Department of Medicine, Faculty of Medicine, University of Malaga, Malaga, Spain | [b] Centro de Investigaciones Médico-Sanitarias (C.I.M.E.S), General Foundation University of Malaga, Malaga, Spain | [c] Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA | [d] Department of Endocrinology, Carlos Haya Hospital, Malaga, Spain | [e] The Iowa Consortium for Substance Abuse Research and Evaluation, University of Iowa, Iowa City, IA, USA | [f] Department of Neurology, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA

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: [email protected].

Abstract: Background/Objective:The aim was to assess the neuropsychological performance of a group of middle-aged patients with well-controlled type 2 diabetes mellitus (T2DM) and to examine whether the neuropsychological deficits correlate with structural and functional brain alterations. Methods:We compared 25 subjects with T2DM aged 45–65 years with 25 control participants matched for age, gender, and educational level. The neuropsychological battery was designed to examine executive functions, attention, information processing speed, and verbal memory. Severity of depression was assessed using the Hamilton Depression Rating Scale and cardiovascular risk factors were assessed using the Framingham Cardiovascular Risk Profile Score. The presence of at least one APOEε4 allele was determined. Reduced gray matter density was analyzed using voxel-based morphometry and brain glucose metabolic changes were assessed by 18FDG-PET. Results:T2DM subjects had significantly lower scores than subjects without T2DM in the Trail-making Test B (p < 0.004), Color-Word Stroop test (p < 0.005), Semantic Fluency (p < 0.006), Digit-Symbol modalities test (p < 0.02), Text Recall from the Wechsler Memory Scale (p < 0.0001), Rey-Osterrieth Complex Figure-copy (p < 0.004), and delayed reproduction (p < 0.03). Worse executive functions and memory functioning correlated predominantly with less gray matter density and reduced glucose metabolism in the orbital and prefrontal cortex, temporal (middle gyrus, parahippocampus and uncus), and cerebellum regions (p < 0.001). Conclusions:T2DM subjects presented cognitive dysfunctions compared with controls. Clinical-neuroimaging correlations corresponded to brain changes (reduced gray matter density and glucose metabolism) mainly in fronto-temporal areas.

Keywords: Cognition, dementia, magnetic resonance imaging, mild cognitive impairment, neuropsychology, positron emission tomography, type 2 diabetes mellitus

DOI: 10.3233/JAD-140702

Journal: Journal of Alzheimer's Disease, vol. 42, no. 4, pp. 1337-1346, 2014