ALZHEMIER’S DISEASE (AD)

• Slowly progressive disease of brain.
• Common in 5th & 6th decade.

FEATURES:

• Characterized by memory impairment –> eventually by disturbances in reasoning, planning, language & perception. 
• Cranial changes:
• Characterized by proteins (Apo E4 gene) build-up in brain.
• Build-up manifests in 2 ways:
• As Plaque – 
  • Deposits of protein beta-amyloid accumulating in between nerve cell spaces.
• As Tangles – 
• Deposits of protein accumulating inside nerve cells.
• Widely distributed in cortical structures & hippocampus, but always spare cerebellum.
• Correlates with dementia’s duration & severity.
• Microscopic features:
• Both amyloid plaques & neurofibrillary tangles – Clearly visible by microscopy.
• Plaques – 
  • Dense, mostly insoluble amyloid deposits (beta-peptides & cellular material outside & around neurons).
  • Senile neural plaques correlates & increases with age.
  • Also deposits in vessel walls (cerebral amyloid angiopathy (CAA).
• Tangles (neurofibrillary tangles) – 
  • Aggregates of microtubule-associated protein “tau”.
    • Becomes hyperphosphorylated accumulating inside cells causing severe dementia.
  • Lateral geniculate body resistant to neurofibrillary tangles.

SYMPTOMS:

• Early Stage
  • Mild/early stage.
  • Duration – 2-4 years.
  • Frequent recent memory loss (mainly recent conversations & events).
    • Repeated questions, some problems expressing and understanding language.
  • Difficulty in writing & using objects.
  • Depression & apathy can occur.
  • Drastic personality changes with functional decline.
  • Need reminders for daily activities & difficulties with sequencing impact driving early in this stage.
• Structures of the medial temporal lobe, including hippocampus, entorhinal cortex and amygdala, are involved early in the course and are usually severely atrophied in the later stages.
• Second stage:
  • Middle/moderate stage.
  • Duration – 2-10 years.
  • Can no longer cover up problems. 
  • Pervasive & persistent memory loss impacts life across settings.
  • Associated with depressive symptoms, delusions, apraxia & aphasia.
    • Rambling speech, unusual reasoning, confusion about current events, time, and place. 
  • Potential to become lost in familiar settings, sleep disturbances & mood or behavioral symptoms accelerate.
  • Nearly 80% exhibit emotional & behavioral problems aggravated by stress & change.
    • Slowness, rigidity, tremors, and gait problems impact mobility & coordination. 
  • Need structure, reminders & assistance with daily activities.

• Moderate stage
  • Increased memory loss & confusion.
  • Problems recognizing family & friends.
  • Inability to learn new things.
  • Difficulty carrying out tasks that involve multiple steps (such as getting dressed).
  • Problems coping with new situations.
  • Delusions & paranoia.
  • Impulsive behavior.
  • Damage occurs in areas controlling language, reasoning, sensory processing & conscious thought
•  Last stage
  • Considered severe stage.
  • Duration = 1-3 years.
  • Confused about past & present. 
  • Loss of recognition of familiar people & places.
  • Generally incapacitated with severe to total loss of verbal skills.
  • Unable to care for self.  
  • Falls possible & immobility likely.
  • Problems with swallowing, incontinence & illness.
  • Extreme problems with mood, behavioral problems, hallucinations & delirium.
  • Patients need total support & care.
  • Death due to infections (pneumonia).

DIAGNOSIS 

• Patient history, collateral history from relatives & clinical observations.
• Characteristic neurological & neuropsychological features, without alternative conditions.
• CT, MRI, SPECT, PET- Excludes other cerebral pathology or dementia subtypes.
• Histopathology – Fixative used – 10% buffered neutral formalin.
• Post-mortem analysis:
  • Very high accuracy diagnosis – When brain material is available &can be examined histologically.