Alzheimer's Disease

What is Alzheimer's Disease?

A progressive, degenerative disease affecting the cerebral cortex—the site at which the highest level of neural processing takes place—Alzheimer's disease in individuals younger than age 65 is termed early-onset.

2 Types

Common Alzheimer disease is the type that occurs in most cases, whereas the genetic form of the disease is extremely rare. With genetic Alzheimer disease, signs and symptoms typically develop between ages 30 and 50.

Genetic Type

The genetic type is associated with a mutation in one of three genes located on three different chromosomes: 1, 14, and 21.

Pathophysiology

Alzheimer disease is characterized by beta-amyloid plaques, neurofibrillary tangles, neuronal degeneration, and diffuse atrophy of the cerebral cortex.

• Beta-amyloid plaques occur as the result of accumulation of beta-amyloid—a small fibrillary peptide that builds up in the spaces around synapses.

Beta-amyloid plaque

• In Alzheimer disease, there's too much beta-amyloid present, and the body isn't able to remove it.
• This results in an accumulation of the peptide.
• The beta-amyloid accumulates into fibrils that clump together and form plaques, which effectively kill brain cells and cause a disruption in brain functioning.

Tau Proteins

• Tau protein abnormally twists, causing axons to tangle and leading to the development of neurofibrillary tangles in neuronal cell bodies.
• The plaques and tangles that develop in the brain are found in areas important for memory and intellectual functions.

Hippocampus

• Damage in the brain may start in the hippocampus—the area responsible for memory formation.
• It's believed that this damage begins a decade before signs and symptoms develop.

Early Signs and Symptoms

• Forgetfulness, especially with new information
• Repeatedly asking the same questions
• Difficulty solving basic problems
• Losing track of the date and/or time of year
• Losing track of location and how the person arrived at the location
• Problems with depth perception
• Difficulty with conversations
• Difficulty with word finding
• Difficulty concentrating
• Misplacing items
• Increasingly poor judgment
• Withdrawal from work and/or social situations
• Change in mood and personality
• Increasing difficulty completing familiar tasks
• Repeating stories
• Forgetting names of familiar people
• Wandering, especially at night

Late Symptoms

• Depression
• Severe mood swings and behavior changes
• Increasing agitation and irritability
• Increasing confusion about time, place, and events
• Suspicions about family and friends
• Disinhibition

Stages of Alzheimer Disease

Mild Stage

• The patient begins to have memory loss and cognitive difficulties.
• The patient and/or family members may report:
  • Wandering
  • Getting lost
  • Having difficulty with money/paying bills
  • Repeating questions

Moderate Stage

• Damage in the brain has spread to the areas responsible for language, sensory processes, conscious thought, and reasoning.
• The patient may have:
  • Increased memory loss and confusion
  • Difficulty recognizing friends and family
  • Trouble learning new things
  • Difficulty performing complex tasks

Severe Stage

• Plaques and tangles spread throughout the brain and brain atrophy is present.
• The patient will be bedridden and unable to communicate.
• The body will eventually shut down.

Diagnosis

Diagnosis is based on:

• History and physical examination
• Signs and symptoms
• Cognitive tests
• Blood, urine, and spinal fluid analysis
• Computed tomography (CT) or magnetic resonance imaging (MRI)

Complications

Most of the complications seen with Alzheimer disease arise from immobility, including:

• Aspiration
• Pneumonia and other infections
• Falls
• Fractures
• Skin breakdown (pressure ulcers)
• Malnutrition and dehydration

Management

Alzheimer disease is a progressive disease with no cure.

• Current treatment focuses on:
  • Helping patients maintain mental and physical function
  • Controlling behavior
  • Improving quality of life
  • Slowing disease progression

Pharmacotherapy

Medications that may slow the progression of the disease include:

• Donepezil
• Rivastigmine
• Memantine
• These may only be beneficial for a few months to a few years.

Donepezil

• Works by increasing acetylcholine levels in the brain.

Non-Pharmacological Approaches

In addition to medications, the following may help delay disease progression:

• Physical activity
• Cardiovascular treatment
• Diabetes treatment
• Antioxidants
• Cognitive training