Alzheimer Dementia

Summary

Alzheimer dementia, also known as Alzheimer disease, is a neurodegenerative disease that primarily affects the medial temporal lobe, and in particular, the hippocampus. Early onset Alzheimer dementia is associated with trisomy 21, or Down syndrome. Neurotransmitter changes seen in Alzheimer patients include decreased acetylcholine levels, which may contribute to cognitive impairments.

Patients with Alzheimer dementia generally present with a slow, gradual memory decline, along with impaired planning and visuospatial awareness, which can cause them to get lost in familiar environments. Alzheimer dementia can be definitively diagnosed through histopathology of brain sections under the microscope, which may reveal beta amyloid plaques or deposits of hyperphosphorylated tau proteins known as neurofibrillary tangles. This is not ideal for diagnosing the disease in living patients, where clinical inference is preferred and brain imaging can be used to supplement a diagnosis. These brain scans often reveal diffuse brain atrophy, with enlargement of the surrounding fluid spaces to occupy the space left by the shrunken brain. Finally, Alzheimer dementia can be treated with cholinesterase inhibitors like Donepezil, Rivastigmine, and Galantamine, as well as NMDA receptor antagonists like Memantine.

Key Points

• Alzheimer Dementia (AD)
  • Pathophysiology
    • Widespread neurodegeneration, especially in medial temporal lobe
      • Hippocampus
        • Leads to memory impairments
      • Amygdala
        • Leads to emotional and psychological impairments
      • Entorhinal cortex
    • Risk Factors
      • Increasing age, female gender, family history
      • Early onset associated with Trisomy 21 (Down Syndrome)
        • Due to extra copy of APP (amyloid precursor protein) located on chromosome 21
  • Neurotransmitter Changes
    • Decreased ACh
      • Decreased production in the nucleus basalis of Meynert
        • Thought to be due to decreased choline acetyltransferase activity
      • Decreased ACh and M1 receptor signaling may contribute to cognitive impairments
  • Presentation
    • Gradual memory decline
      • Most common cause of dementia in the elderly
      • Insidious onset; slowly progressive memory decline (contrast vs. vascular dementia which exhibits stepwise decline)
      • Declarative episodic memory is especially impaired (memory of events that occurred in a specific time and place)
    • Impaired planning and organization
      • Executive dysfunction likely due to degeneration of cortical neurons
    • Visuospatial impairment (getting lost)
      • Patients may get lost in their home, neighborhood, or other familiar environments
    • Language deficits
    • Behavioral and psychological impairment
      • Apathy, social isolation, irritability
  • Diagnosis
    • Clinical diagnosis of exclusion
      • Other medical causes of dementia (e.g. stroke) must be ruled out first
      • Brain biopsies are usually not indicated, so a definitive neuropathological diagnosis is usually only possible post-mortem
    • Neuropathology/Brain Biopsy
      • Extracellular beta-amyloid plaques
        • Also known as neuritic plaques
        • Amyloid exhibits apple-green birefringence when stained with Congo red and viewed under polarized light
          • Amyloid angiopathy may occur when deposits occur along cerebral vessels (can lead to hemorrhage)
      • Intraneuronal neurofibrillary tangles
        • Composed of hyperphosphorylated tau protein
    • Gross Pathology/Brain Imaging
      • Diffuse brain atrophy
        • May be described as “hydrocephalus ex vacuo”
          • Relative enlargement of CSF spaces due to decrease in brain volume
    • Cognitive Testing
      • Montreal Cognitive Assessment (MoCA)
      • Mini Mental Status Exam
  • Treatment
    • Donepezil, Rivastigmine, Galantamine
      • Cholinesterase inhibitors (increases ACh)
      • Typically used in mild-moderate AD
    • Memantine
      • Neuroprotective N-methyl-D-aspartate (NMDA) receptor antagonist
      • Used in moderate to severe AD
      • May prevent neuron excitotoxicity contributing to AD