Alzheimer disease

Pathophysiology

• Build-up of beta amyloid plaques with neurofibrillary tangles
• Degeneration of the transentorhinal region, followed by hippocampus then lateral and posterior temporal and parietal neocortex

Differential Diagnosis

• See Dementia

Epidemiology

• Most prevalent dementia syndrome

Risk Factors

• Age
• Gene mutations: APP, PS-1, PS-2, and Apo epsilon-4

Clinical Presentation

• History
  • Typically begins with memory loss
  • Later, aphasia and navigational problems
• Signs & Symptoms

Management

Symptomatic Treatments

• Cholinesterase inhibitors for AD with stroke, and as an option for Parkinson disease dementia
  • Not indicated in vascular dementia
  • No specific preferred cholinesterase inhibitor
  • Modest improvements in cognition but does not delay nursing home
  • Side effects include bradycardia, syncope, GI intolerance, urinary incontinence, and abnormal dreams
    • NMS and rhabdomyolysis are rare but reported
• Combination with memantine appears safe
  • Can either add memantine to cholinesterase inhibitor, or replace it
• Trial of antidepressent can be considered in patients with depression, severe dysthymia, or emotional lability
• Antipsychotics should be reserved for cases where the patient's agitated causes a risk of harm to themselves or others

Discontinuation of Acetylcholinesterase Inhibitors

• May worsen cognition, but should be considered if there are adverse side effects, or the dementia has progressed past the point where they would be helpful
• If stopped for non-effectiveness, they should be tapered before stopping, then monitored for cognitive decline

Further Reading

• Canadian Dementia Guidelines CCCDTD4 2012