The Clinical Phenotype of Vascular Cognitive Impairment in Patients with Type 2 Diabetes Mellitus

Article type: Research Article

Authors: Groeneveld, Onno N.^{a; *} | Moneti, Costanza^a | Heinen, Rutger^a | de Bresser, Jeroen^{b; c} | Kuijf, Hugo J.^d | Exalto, Lieza G.^a | Boomsma, Jooske M.F.^{a; e} | Kappelle, L.Jaap^a | Barkhof, Frederik^{f; g} | Prins, Niels D.^h | Scheltens, Philip^h | van der Flier, Wiesje M.^{h; i} | Biessels, Geert Jan^a | and on behalf of the TRACE-VCI study group

Affiliations: [a] Department of Neurology, Brain Center Rudolph Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands | [b] Department of Radiology, University Medical Center Utrecht, Utrecht University, Utrecht,the Netherlands | [c] Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands | [d] Image Sciences Institute, University Medical Center Utrecht, Utrecht, the Netherlands | [e] Department of Neurology, Onze Lieve Vrouwe Gasthuis (OLVG) West, Amsterdam, Netherlands | [f] Department of Radiology and Nuclear Medicine, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands | [g] Institutes of Neurology & Healthcare Engineering, University College London (UCL), London, United Kingdom | [h] Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands | [i] Department of Epidemiology and Biostatistics, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands

Correspondence: [*] Correspondence to: Onno N. Groeneveld, Brain Center Rudolf Magnus, Department of Neurology, G03.232, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands. Tel.: +31 887555555; Fax: +31 302542100; E-mail: [email protected].

Abstract: Background:Type 2 diabetes mellitus (T2DM) increases the risk of vascular cognitive impairment (VCI). It is unknown which type of vascular lesions and co-morbid etiologies, in particular Alzheimer’s disease pathology, are associated with T2DM in patients with VCI, and how this relates to cognition and prognosis. Objective:To compare brain MRI and cerebrospinal fluid (CSF) markers, cognition, and prognosis in patients with possible VCI with and without T2DM. Methods:We included 851 memory clinic patients with vascular brain injury on MRI (i.e., possible VCI) from a prospective cohort study (T2DM: n = 147, 68.4±7.9 years, 63% men; no T2DM: n = 704, 67.6±8.5 years, 52% men). At baseline, we assessed between-group differences in brain MRI abnormalities, CSF markers of Alzheimer’s disease, and cognitive profile. After two years follow-up, we compared occurrence of cognitive decline, stroke, and death. Results:The distribution of clinical diagnoses did not differ between patients with and without T2DM. T2DM patients had more pronounced brain atrophy (total and white matter volume), and more lacunar infarcts, whereas microbleeds were less common (all p < 0.05). CSF amyloid-β levels were similar between the groups. T2DM patients performed worse on working memory (effect size: – 0.17, p = 0.03) than those without, whereas performance on other domains was similar. During follow-up, risk of further cognitive decline was not increased in T2DM.∥Conclusion: In patients with possible VCI, presence of T2DM is related to more pronounced brain atrophy and a higher burden of lacunar infarcts, but T2DM does not have a major impact on cognitive profile or prognosis.∥

Keywords: Cerebrospinal fluid, magnetic resonance imaging, prognosis, type 2 diabetes mellitus, vascular brain injury

DOI: 10.3233/JAD-180914

Journal: Journal of Alzheimer's Disease, vol. 68, no. 1, pp. 311-322, 2019