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Brain MRI in diabetes
Functional and structural neuroimaging in type 2 diabetes Geert Jan Biessels Vascular Cognitive Impairment Group Department of Neurology UMC Utrecht, The Netherlands diabetes cognitive dysfunction brain structural changes dementia GJB – ECNP 2/36 Diabetes and dementia Systematic review Ott 1999 Brayne 1998 Peila 2002 MacKnight 2002 Xu 2004 Leibson 1997 Hassing 2002 0.5 1 2 5 10 independent of other vascular risk factors GJB – ECNP 3/36 Biessels GJ, et al. Lancet Neurol 2006;5(1):64–74. Cognition in non-demented T2DM patients: meta analyses DM2 relative to controls: subtle decrements in – executive function – processing speed – verbal memory – visual memory GJB – ECNP 4/36 Palta, et al, JINS 2014; 20: 278-91 Cognition in non-demented DM patients: meta analyses p40 verbal memory domain Palta, et al, JINS 2014; 20: 278-91 Cognition in non-demented T2DM patients Utrecht Diabetic Encephalopathy Study CON, n=38 T2DM, n=68 4 years GJB – ECNP 6/36 van den Berg E, et al. Diabetologia 2010;53(1):58–65. Trajectories cognitive dysfunction T2DM patients compiled results of >30 x-sect & longit studies age-adjusted normalized cognitive performance no DM impaired cognition GJB – ECNP 7/36 age (years) Biessels, et al. Lancet Diabetes & Endo 2014 Trajectories cognitive dysfunction T2DM patients compiled results of >30 x-sect & longit studies age-adjusted normalized cognitive performance no DM cognitive performance type 2 diabetes impaired cognition GJB – ECNP 8/36 •magnitude largely age independent •slow progression relative to controls age (years) Biessels, et al. Lancet Diabetes & Endo 2014 1 dementia incidence no diabetes diabetes cognitive performance no diabetes diabetes 60 0 40 -1 •two “types” of cognitive dysfunction •not a continuum impaired cognition -2 •different etiologies? •effects may be additive: ‘double age hit’ 20 30 40 50 20 dementia incidence (per 1000 person years) cognitive performance (age-adj. z-score) Trajectories cognitive dysfunction T2DM patients 0 60 70 80 GJB – ECNP 9/36 Biessels, et al. Lancet Diabetes & Endo 2014 diabetes cognitive dysfunction brain structural changes dementia Brain volumetry on MRI FLAIR IR Segmentation Segmentation using k-NN clustering: • White Matter • Gray Matter • Lateral Ventricles • CSF • White Matter Lesion Brain MRI in T2DM: volumetry 82 Total brain volume 22 Peripheral CSF CON, n=28 T2DM, n=55 %ICV %ICV 80 78 20 18 76 74 BL 16 FU Ventricular volume 0.70 Utrecht 0.55 Diabetic 0.40 Encephalopathy Study 0.25 2.60 %ICV %ICV FU White matter lesions 3.20 2.00 1.40 BL BL GJB – ECNP 12/36 FU 0.10 BL FU De Bresser, Diabetes Care 2010;33(6):1309-1314. Brain MRI in T2DM: volumetry Total brain volume Ventricular volume Grey matter volume CON, n=574 T2DM, n=89 SMART Study: patients with symptomatic atherosclerotic disease GJB – ECNP 13/36 Kooistra et al J Neurol Sci 2013 Brain MRI in T2DM: distribution volume loss • medial temporal, anterior cingulate, and medial frontal lobes • related to cognitive performance GJB – ECNP 14/36 Moran et al Diabetes Care 2013 Brain MRI in T2DM: volumetry: hippocampus hippocampus to total brain volume ratio GJB – ECNP 15/36 Wisse et al J Neurol Sci 2014 vascular burden in dementia: MRI markers of small vessel disease GJB – ECNP 16/36 Wardlaw Lancet Neurology 2013 Small vessel disease on Brain MRI in T2DM • Infarcts OR: 1.3–2.3 • Modest increase volume white matter hyperintensities GJB – ECNP 17/36 Van Harten B, et al. Diabetes Care 2006;29:2539–48 Biessels & Reijmer, Diabetes 2014 Abnormalities on brain MRI and cognition in T2DM GJB – ECNP 18/36 Qiu et al Ann Neurol 2014 Abnormalities on brain MRI and cognition in T2DM GJB – ECNP 19/36 Qiu et al Ann Neurol 2014 Emerging brain imaging techniques in T2DM GJB – ECNP 20/36 Microvascular lesions: 7T MRI microbleed microinfarct 7Tesla MRI GJB – ECNP 21/36 Microvascular lesions: 7T MRI 38% 48% microinfarcts GJB – ECNP 22/36 41% 33% microbleeds Brundel et al Diabetes 2014 diffusion tensor imaging (DTI) White matter GJB – ECNP 23/36 tractography diffusion tensor imaging •microstructural abnormalities white matter pathways GJB – ECNP 24/36 Reijmer, Diabetes Care 2013 network approach Social network: facebook GJB – ECNP 25/36 ‘Small-world’ network approach •network disturbances – strong correlate cognitive dysfunction in T2DM GJB – ECNP 26/36 Reijmer, diabetes 2013 fMRI GJB – ECNP 27/36 Iannetti et al MRI 2007 fMRI GJB – ECNP 28/36 Iannetti et al MRI 2007 fMRI –T2DM GJB – ECNP 29/36 Brain perfusion & metabolism ASL, MRS, PET, SPECT…. GJB – ECNP 30/36 European Neuropsychopharmacology Conclusions GJB – ECNP 31/36 Brain MRI in T2DM summary GJB – ECNP 32/36 Biessels & Reijmer, Diabetes 2014 Brain MRI in T2DM summary GJB – ECNP 33/36 Biessels & Reijmer, Diabetes 2014 Brain MRI in T2DM open questions type 2 diabetes who is at risk? etiology cognitive dysfunction brain structural changes dementia treatment Alzheimer Centre, Amsterdam Barkhof Van der Flier Scheltens VCI study group – collaborating departments Neurology Biesbroek Biessels Bouvy Brundel Exalto Groeneveld Kappelle Luitse van Veluw Verwer Neuropsychology Van den Berg Heringa Postma Reijmer Ruis Schoo van Zandvoort Radiology-ISI de Bresser Hendrikse van der Kolk Kuijf Leemans Luijten Mali van Seeters Velthuis Viergever Vincken Zwanenburg Psychiatry Van den Heuvel Geriatrics Koek Julius Centre Algra Blom Geerlings Janssen Koekkoek Kooistra Rutten Wisse Hoorn Study Dekker Nijpels Stehouwer Kaiser Permanente, Oakland, California Whitmer Rehabilitation Visser-Meily Funding: Thank you! Geert Jan Biessels Vascular Cognitive Impairment Group Department of Neurology UMC Utrecht The Netherlands Thank you! Geert Jan Biessels Vascular Cognitive Impairment Group Department of Neurology UMC Utrecht The Netherlands Disclosure Geert Jan Biessels Consultancies: Research support: Lectures: Boehringer Ingelheim, Takeda Pharmaceuticals Boehringer Ingelheim Lilly, Philips Healthcare Financial compensation for these services is transferred to the UMC Utrecht, not to GJB Other research support: • VIDI grant 91711384 from the Netherlands Organisation for Health Research and Development (ZonMw) • Grant 2010T073 from the Netherlands Heart Foundation (NHF) • International Foundation Alzheimer’s Research (ISAO) • Dutch Diabetes Foundation (Diabetesfonds) • Brain Foundation (Hersenstichting Nederland) • European Foundation for the Study of Diabetes (EFSD) • High Potential Grant from Utrecht University
