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

Onno N. Groeneveld*, Costanza Moneti, TRACE-VCI Study Grp, Rutger Heinen, Jeroen de Bresser, Hugo J. Kuijf, Lieza G. Exalto, Jooske M. F. Boomsma, L. Jaap Kappelle, Frederik Barkhof, Niels D. Prins, Philip Scheltens, Wiesje M. van der Flier, Geert Jan Biessels, M. R. Benedictus, J. Bremer, J. Goos, A. E. Leeuwis, J. Leijenaar, B. M. TijmsH. Vrenken, C. E. Teunissen, E. van den Berg, D. A. Ferro, C. J. M. Frijns, O. N. Groeneveld, N. M. van Kalsbeek, J. H. Verwer, H. L. Koek, H. M. Boss, H. C. Weinstein

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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-beta 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.

Original languageEnglish
Pages (from-to)311-322
Number of pages12
JournalJournal of Alzheimers Disease
Issue number1
Publication statusPublished - 2019

Bibliographical note

The TRACE-VCI study is supported by Vidi grant 917.11.384 and Vici Grant 918.16.616 from ZonMw,
The Netherlands, Organisation for Health Research and Development, and grant 2010T073 from the
Dutch Heart Association to Geert Jan Biessels. Research of the Alzheimer Center Amsterdam
is part of the neurodegeneration research program of Amsterdam Neuroscience. The Alzheimer Center Amsterdam is supported by Stichting Alzheimer
Nederland and Stichting VUmc fonds. The clinical database structure was developed with funding from
Stichting Dioraphte. Frederik Barkhof is supported by the NIHR UCLH Biomedical Research Center.
Members of the TRACE-VCI study group are (in alphabetical order, per department): VU University
Medical Centre, Amsterdam, The Netherlands: 1) Alzheimer Centre and Department of neurology: MR
Benedictus, J Bremer, WM van der Flier, J Goos, AE Leeuwis, J Leijenaar, ND Prins, P Scheltens,
BM Tijms; 2) Department of Radiology and Nuclear Medicine: F Barkhof, H Vrenken; 3) Department of
Clinical Chemistry: CE Teunissen. University Medical Centre Utrecht, Utrecht, The
Netherlands: 1) Department of Neurology: E van den Berg, GJ Biessels, JMF Boomsma, LG Exalto, DA
Ferro, CJM Frijns, ON Groeneveld, R Heinen, NM van Kalsbeek, JH Verwer; 2) Department of Radiology: J de Bresser; Image Sciences Institute: HJ Kuijf;
3) Department of Geriatrics: HL Koek. Onze Lieve Vrouwe Gasthuis (OLVG) West, Amsterdam, The Netherlands: 1) Department of Neurology: JMF Boomsma, HM Boss, HC Weinstein.
Authors’ disclosures available online (https://
SUPPLEMENTARY MATERIAL The supplementary material is available in the electronic version of this article:


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