Diabetes Metab J.  2019 Oct;43(5):560-567. 10.4093/dmj.2019.0153.

Contributing Factors to Diabetic Brain Injury and Cognitive Decline

• Verma N
• Despa F

• KMID: 2460949
• DOI: http://doi.org/10.4093/dmj.2019.0153

Abstract

The link of diabetes with co-occurring disorders in the brain involves complex and multifactorial pathways. Genetically engineered rodents that express familial Alzheimer's disease-associated mutant forms of amyloid precursor protein and presenilin 1 (PSEN1) genes provided invaluable insights into the mechanisms and consequences of amyloid deposition in the brain. Adding diabetes factors (obesity, insulin impairment) to these animal models to predict success in translation to clinic have proven useful at some extent only. Here, we focus on contributing factors to diabetic brain injury with the aim of identifying appropriate animal models that can be used to mechanistically dissect the pathophysiology of diabetes-associated cognitive dysfunction and how diabetes medications may influence the development and progression of cognitive decline in humans with diabetes.

Keyword

Dementia; Diabetes mellitus; Obesity

MeSH Terms

Amyloid
Brain Injuries*
Brain*
Dementia
Diabetes Mellitus
Humans
Insulin
Models, Animal
Obesity
Plaque, Amyloid
Presenilin-1
Rodentia
Amyloid
Insulin
Presenilin-1

Figure

• 

  Fig. 1 Risk factors for cognitive dysfunctions in diabetes. Figure showing main risk factors involved in cognitive dysfunction in diabetes. These risk factors may be associated with different types of cognitive dysfunction in diabetes.

• 

  Fig. 2 Proposed mechanism underlying the impact of amylin dyshomeostasis on the brain. Prediabetic hyperamylinemia in humans promotes amylin oligomerization within the pancreatic secretory pathway and consequent secretion of oligomerized amylin in the blood (amylin dyshomeostasis), which causes brain microhemorrhages leading to neuroinflammation and hypoxic-ischemic brain injury. BBB, blood-brain barrier; 4HNE, 4 hydroxynonenal; MDA, malondialdehyde; IL-1β, interleukin 1β.

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