Journal of Neural Transmission

, Volume 124, Issue 11, pp 1431–1454 | Cite as

The diabetic brain and cognition

  • Peter RiedererEmail author
  • Amos D. Korczyn
  • Sameh S. Ali
  • Ovidiu Bajenaru
  • Mun Seong Choi
  • Michael Chopp
  • Vesna Dermanovic-Dobrota
  • Edna Grünblatt
  • Kurt A. Jellinger
  • Mohammad Amjad Kamal
  • Warda Kamal
  • Jerzy Leszek
  • Tanja Maria Sheldrick-Michel
  • Gohar Mushtaq
  • Bernard Meglic
  • Rachel Natovich
  • Zvezdan Pirtosek
  • Martin Rakusa
  • Melita Salkovic-Petrisic
  • Reinhold Schmidt
  • Angelika Schmitt
  • G. Ramachandra Sridhar
  • László Vécsei
  • Zyta Beata Wojszel
  • Hakan Yaman
  • Zheng G. Zhang
  • Tali Cukierman-Yaffe
Neurology and Preclinical Neurological Studies - Review Article


The prevalence of both Alzheimer’s disease (AD) and vascular dementia (VaD) is increasing with the aging of the population. Studies from the last several years have shown that people with diabetes have an increased risk for dementia and cognitive impairment. Therefore, the authors of this consensus review tried to elaborate on the role of diabetes, especially diabetes type 2 (T2DM) in both AD and VaD. Based on the clinical and experimental work of scientists from 18 countries participating in the International Congress on Vascular Disorders and on literature search using PUBMED, it can be concluded that T2DM is a risk factor for both, AD and VaD, based on a pathology of glucose utilization. This pathology is the consequence of a disturbance of insulin-related mechanisms leading to brain insulin resistance. Although the underlying pathological mechanisms for AD and VaD are different in many aspects, the contribution of T2DM and insulin resistant brain state (IRBS) to cerebrovascular disturbances in both disorders cannot be neglected. Therefore, early diagnosis of metabolic parameters including those relevant for T2DM is required. Moreover, it is possible that therapeutic options utilized today for diabetes treatment may also have an effect on the risk for dementia. T2DM/IRBS contribute to pathological processes in AD and VaD.


Vascular dementia Alzheimer’s disease Diabetes mellitus Insulin resistance Cognition Neurotransmitters in dementia Diabetic brain Pathology of dementia Experimental model of dementia Neurogenesis in dementia Epidemiology of dementive disorders Imaging in dementia 






Alzheimer’s disease


Advanced glycation end products


Proline-rich AKT1 substrate 1


RAC-alpha serine/threonine-protein kinase


RAC-beta serine/threonine-protein kinase


Beta-amyloid precursor protein


Apolipoprotein E ϵ4




Adenosine triphospate


Blood brain barrier






Brain insulin resistance


Cerebral blood flow


Chronic brain hypoperfusion


Cerebrospinal fluid




Cerebrovascular reactivity


Diabetes mellitus


Desoxyribonucleic acid




Fat-mass and obesity-associated gene


Gadolinium-based MRI contrast agent


Glucagon-like peptide 1


Glucose transporter 3


Grey matter


Glycogen synthase kinase 3 β


Homeostatic model assessment of insulin resistance




Insulin degrading enzyme




Insulin-like growth factor 1 receptor


Insulin receptor


Insulin resistant brain state


Insulin receptor subunit β


Insulin receptor substrate-1


Serin-phosphorylated insulin receptor substrate-1


Insulin receptor substrate-2


Interstitial fluid


Kynurenine aminotransferase


Kynurenic acid


Mild cognitive impairment


Magnet resonance imaging


Mechanistic target of rapamycin


Oxidative stress


Pre-clinical AD


Positron emission tomography


Postprandial glycemia


Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta isoform


Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta






Phosphatidylinositol (3,4,5)-triphosphate


Peroxisome proliferator-activated receptor gamma




Peptide YY


Phosphoprotein p53


Quinolinic acid


Receptor for AGEs


Ribonucleic acid


Reactive oxygen species


Sporadic Alzheimer’s disease


Sodium/glucose cotransporter 2




Type 2 diabetes mellitus


Type 1 diabetes mellitus


Vascular dementia


White matter



Hakan Yaman will be supported by the Akdeniz University Research Management Unit.


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Copyright information

© Springer-Verlag GmbH Austria 2017

Authors and Affiliations

  • Peter Riederer
    • 1
    Email author
  • Amos D. Korczyn
    • 16
  • Sameh S. Ali
    • 2
  • Ovidiu Bajenaru
    • 3
  • Mun Seong Choi
    • 4
  • Michael Chopp
    • 5
  • Vesna Dermanovic-Dobrota
    • 7
  • Edna Grünblatt
    • 8
    • 9
    • 10
  • Kurt A. Jellinger
    • 11
  • Mohammad Amjad Kamal
    • 13
    • 14
    • 15
  • Warda Kamal
    • 12
  • Jerzy Leszek
    • 17
  • Tanja Maria Sheldrick-Michel
    • 19
  • Gohar Mushtaq
    • 20
  • Bernard Meglic
    • 18
  • Rachel Natovich
    • 6
  • Zvezdan Pirtosek
    • 21
  • Martin Rakusa
    • 22
  • Melita Salkovic-Petrisic
    • 23
  • Reinhold Schmidt
    • 24
  • Angelika Schmitt
    • 25
  • G. Ramachandra Sridhar
    • 26
  • László Vécsei
    • 27
  • Zyta Beata Wojszel
    • 28
  • Hakan Yaman
    • 29
  • Zheng G. Zhang
    • 5
    • 29
  • Tali Cukierman-Yaffe
    • 6
  1. 1.Center of Mental Health, Department Psychiatry, Psychosomatics and PsychotherapyUniversity Hospital WürzburgWürzburgGermany
  2. 2.Center for Aging and Associated Diseases, Helmy Institute of Medical ScienceZewail City of Science and TechnologyGizaEgypt
  3. 3.Department of Neurology, Neurosurgery and PsychiatryUniversity of Medicine and Pharmacy Carol Davila BucharestBucharestRomania
  4. 4.Department of NeurologyHallym HospitalIncheon-siKorea
  5. 5.Department of NeurologyHenry Ford HospitalDetroitUSA
  6. 6.The Center for Successful Aging with Diabetes, Endocrinology Institute, Gertner Institute, Sheba Medical Center, Epidemiology D., Sackler School of MedicineTel Aviv UniversityTel AvivIsrael
  7. 7.Clinical Hospital Merkur-University, Clinic Vuk VrhovacZagrebCroatia
  8. 8.Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric HospitalUniversity ZurichZurichSwitzerland
  9. 9.Neuroscience Center ZurichUniversity of Zurich and the ETH ZurichZurichSwitzerland
  10. 10.Zurich Center for Integrative Human PhysiologyUniversity of ZurichZurichSwitzerland
  11. 11.Institute of Clinical NeurobiologyViennaAustria
  12. 12.Biomediotronics, EnzymoicHebershamAustralia
  13. 13.King Fahd Medical Research Center, King Abdulaziz UniversityJeddahSaudi Arabia
  14. 14.EnzymoicsHebershamAustralia
  15. 15.Novel Global Community Educational FoundationSydneyAustralia
  16. 16.Department of NeurologyTel Aviv UniversityRamat AvivIsrael
  17. 17.Department of PsychiatryWroclaw Medical UniversityWroclawPoland
  18. 18.Department of NeurologyUniversity Medical Center LjubljanaLjubljanaSlovenia
  19. 19.Chair of Psychiatry and Head of the Odense Brain, Research Center, Department of Psychiatry OdenseUniversity of Southern DenmarkOdense CDenmark
  20. 20.Department of Biochemistry, College of ScienceKing Abdulaziz UniversityJeddahSaudi Arabia
  21. 21.Department of NeurologyUniversity LjubljanaLjubljanaSlovenia
  22. 22.Department of NeurologyUniversity Medical Centre MariborMariborSlovenia
  23. 23.Department of PharmacologyUniversity of Zagreb School of MedicineZagrebCroatia
  24. 24.Department of NeurologyMed. Univ. GrazGrazAustria
  25. 25.Labor für translationale Neurowissenschaften, der Klinik und Poliklinik für Psychiatrie, Psychosomatik und PsychotherapieUniversitätsklinikum WürzburgWürzburgGermany
  26. 26.Endocrine and Diabetes CentreVisakhapatnamIndia
  27. 27.Department of Neurology and MTA-SZTE Neuroscience Research Group, Faculty of Medicine, Albert Szent-Györgyi Clinical CenterUniversity of SzegedSzegedHungary
  28. 28.Department of GeriatricsMedical University of BialystokBialystokPoland
  29. 29.Department of Family Medicine, Faculty of MedicineAkdeniz UniversityAntalyaTurkey

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