Dementia

• What is delirium?

  A state of mental confusion that starts suddenly & is caused by a physical condition of some sort.

  It is also called an 'acute confusional state'.
• What is the central hypothesis surrounding delirium?

  Cerebral Metabolic Insufficiency hypothesis
• What is the 'cerebral metabolic insufficiency' hypothesis?

  Astrocytes transport glucose (more than needed) into cell via GLUT1 -> glycolysis -> excess pyruvate is converted into lactate and shuttled (lactate shuttle) out of the cell into nearby neurons -> reconverted into pyruvate and used for oxidative phosphorylation to produce ATP

  Neurons have an extremely high metabolic rate, so their metabolism is very susceptible to interruptions in vasculature

  When there is hypoxia of neurons -> pyruvate is not used for oxidative phosphorylation, so is converted back into lactate and excreted
• What are astrocytes?

  Most common glial cell type within the brain
• Peripheral inflammation is a well-established trigger of delirium.
• Delirium is usually a secondary consequence of infction.
• How does inflammation lead to neuronal dysfunction?

  Inflammatory molecules activate quiescent microglia -> primed microglia -> secretions of ROS & NO -> neuronal dysfunction & hypoxia

  Primed microglia also prime astrocytes -> attract more immune cells -> positive feedback loop
• Mechanisms that cause delirium, can also accelerate dementia.
• What drugs can exacerbate delirium & how?


  GABAergic sedatives

  Anticholinergic drugs

  Antihistamine drugs

  -> due to neuronal disturbances
• What are the 2 most common subtypes of dementia?

  Alzheimer's disease

  Vascular dementia
• What is the difference between the presentation of Alzheimer's disease & vascular dementia?


  Vascular dementia has an abrupt onset & stepwise progression

  Alzheimer's disease has a gradual onset & gradual progression

  
• Both Alzheimer's disease & vascular dementia are progressive, though cerebrovascular disease results in multiple small infarcts and a more discontinuous progression.
• Which subtypes of dementia are shown in the following images?

  1. Dementia with Lewy bodies
  2. Alzheimer's disease
  3. Frontotemporal dementia
  4. Vascular dementia
  5. Parkinson's disease