Dementia: Alzheimer's Type

Alzheimer's: Intro & Epi - Old Timer's Foe

• Definition: Alzheimer's Disease (AD) is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills.
• It's characterized by insidious onset and gradual cognitive decline, eventually impairing activities of daily living (ADLs).
• Most common type: AD accounts for ~60-80% of all dementia cases, making it the leading cause.
• Epidemiology: Prevalence sharply ↑ with age, approximately doubling every 5 years after age 65.

⭐ Age is the strongest non-modifiable risk factor for Alzheimer's Disease.

Alzheimer's: Pathophysiology - Brain's Sticky Mess

• Protein Misfolding:
  • Amyloid-β (Aβ) plaques: Extracellular. Formed from Amyloid Precursor Protein (APP). Disrupt neuronal communication.
  • Tau neurofibrillary tangles (NFTs): Intracellular. Hyperphosphorylated tau protein. Cause microtubule dysfunction, neuronal death.
• Genetic Links:
  • APOE ε4 allele: Prime genetic risk for late-onset AD.
  • Early-onset AD: Mutations in APP, PSEN1, PSEN2. 📌 "APPsolutely PSENile 1 & 2".
• Neurochemical Changes:
  • Acetylcholine (ACh) ↓: Due to cholinergic neuron loss (Nucleus Basalis of Meynert). Impairs cognition.

⭐ Early pathology targets hippocampus & entorhinal cortex, impacting memory formation.

Alzheimer's: Clinical Features - Mind's Slow Fade

• Early Stage:
  • Anterograde memory loss: Difficulty recalling recent events and learning new information.
  • Anomia: Word-finding problems, often with circumlocution.
• Later Stage (Progressive Deficits):
  • 📌 The "A's":
    • Amnesia: Worsens, affecting recent/remote memory.
    • Aphasia: Impaired language (expression/comprehension).
    • Apraxia: Difficulty with skilled motor tasks (e.g., using cutlery).
    • Agnosia: Inability to recognize familiar objects/faces.
  • Executive Dysfunction: Impaired planning, decision-making, abstraction.
  • BPSD: Agitation, apathy, depression, delusions, wandering.

⭐ Visuospatial dysfunction (e.g., getting lost in familiar surroundings, difficulty with dressing or copying diagrams) is a key early indicator.

Clinical Staging & Progression (MMSE based):

Alzheimer's: Diagnosis - Spotting the Signs

• Core: NINCDS-ADRDA criteria for probable Alzheimer's dementia.

• Screening: MMSE/MoCA for screening and tracking cognitive decline.

• CSF Biomarkers: Aβ42 amyloid ↓, Total Tau (T-tau)↑, Phosphorylated Tau (p-Tau)↑.

• Neuroimaging:

  • MRI/CT: Medial temporal lobe atrophy (esp. hippocampus, entorhinal cortex).
  • PET: Shows amyloid/tau pathology; FDG reveals temporoparietal hypometabolism.

• Key Differentials:

Alzheimer's: Management - Easing the Journey

• Pharmacological:
  • Cholinesterase Inhibitors (AChEIs): Donepezil (5-10mg OD), Rivastigmine, Galantamine.
    • Indication: Mild-moderate AD. MOA: ↑ Acetylcholine. Side Effects: GI upset, bradycardia.
  • NMDA Antagonist: Memantine (start 5mg, target 20mg OD).
    • Indication: Moderate-severe AD. MOA: Blocks glutamate excitotoxicity. Side Effects: Dizziness, headache.

⭐ AChEIs (Donepezil, Rivastigmine, Galantamine) are primary for mild-moderate AD; Memantine for moderate-severe.

• Non-Pharmacological:
  • Cognitive stimulation therapy, reality orientation.
  • Behavioral & Psychological Symptoms of Dementia (BPSD) Management: Non-pharmacological first.
  • Essential: Caregiver education & support, respite care.

High‑Yield Points - ⚡ Biggest Takeaways

• Most common dementia, marked by insidious onset and progressive decline.
• Early memory loss (anterograde amnesia) is the primary symptom.
• Pathophysiology: Amyloid-β plaques (extracellular) and Tau tangles (intraneuronal).
• APOE ε4 allele significantly increases risk for late-onset AD.
• Medial temporal lobe atrophy (hippocampus, entorhinal cortex) is a key neuroimaging finding.
• Treatment: Cholinesterase inhibitors (Donepezil) for mild-moderate; Memantine for moderate-severe stages.
• Diagnosis is clinical, supported by cognitive tests and neuroimaging; definitive by autopsy.