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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

Abstract

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.

Keywords

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 

Abbreviations

Beta-amyloid-protein

AChE

Acetylcholinesterase

AD

Alzheimer’s disease

AGEs

Advanced glycation end products

AKT1s1

Proline-rich AKT1 substrate 1

AKT-1

RAC-alpha serine/threonine-protein kinase

AKT-2

RAC-beta serine/threonine-protein kinase

APP

Beta-amyloid precursor protein

APOE ϵ4

Apolipoprotein E ϵ4

AQP4

Aquaporin-4

ATP

Adenosine triphospate

BBB

Blood brain barrier

BChE

Butyrylcholinesterase

BHB

Beta-hydroxybutyrate

BIR

Brain insulin resistance

CBF

Cerebral blood flow

CBH

Chronic brain hypoperfusion

CSF

Cerebrospinal fluid

Ct

Control

CVR

Cerebrovascular reactivity

DM

Diabetes mellitus

DNA

Desoxyribonucleic acid

FDG

Fluorodeoxyglucose

FTO

Fat-mass and obesity-associated gene

Gd-DTPA

Gadolinium-based MRI contrast agent

GLP-1

Glucagon-like peptide 1

GLUT3

Glucose transporter 3

GM

Grey matter

GSK3β

Glycogen synthase kinase 3 β

HOMA-IR

Homeostatic model assessment of insulin resistance

HNE

4-Hydroxynonenal

IDE

Insulin degrading enzyme

ICV

Intracerebroventricular

IGF-1R

Insulin-like growth factor 1 receptor

IR

Insulin receptor

IRBS

Insulin resistant brain state

IRβ

Insulin receptor subunit β

IRS1

Insulin receptor substrate-1

IRS-1pS616

Serin-phosphorylated insulin receptor substrate-1

IRS2

Insulin receptor substrate-2

ISF

Interstitial fluid

KAT

Kynurenine aminotransferase

KYNAC

Kynurenic acid

MCI

Mild cognitive impairment

MRI

Magnet resonance imaging

mTOR

Mechanistic target of rapamycin

OS

Oxidative stress

PCAD

Pre-clinical AD

PET

Positron emission tomography

PG

Postprandial glycemia

PIK3CB

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

PIK3CD

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

PI3

Phosphatidylinositol-3-kinase

PI3K

Phosphoinositid-3-kinase

PIP3

Phosphatidylinositol (3,4,5)-triphosphate

PPARγ

Peroxisome proliferator-activated receptor gamma

P-Tau

Phospho-Tau-Protein

PYY

Peptide YY

P53

Phosphoprotein p53

QA

Quinolinic acid

RAGE

Receptor for AGEs

RNA

Ribonucleic acid

ROS

Reactive oxygen species

sAD

Sporadic Alzheimer’s disease

SGLT2

Sodium/glucose cotransporter 2

STZ

Streptozotocin

T2DM

Type 2 diabetes mellitus

T1DM

Type 1 diabetes mellitus

VaD

Vascular dementia

WM

White matter

Notes

Acknowledgements

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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