What is Alzheimer’s disease?

Background

• Alzheimer’s disease slowly and progressively destroys brain cells.
• It was first described by Alois Alzheimer in 1906 after he carried out an autopsy on the brain of a 55 year old woman.
  • This woman had died after several years of progressive mental decline, characterised by confusion and memory loss.
  • In the part of the brain responsible for reasoning and memory he found a strange bundle of nerves and cellular debris. He concluded that these were responsible for her condition.
• Alzheimer’s is the single most common cause of dementia (60-80 per cent). It affects about 10 per cent of people aged over 65 and 20 per cent of those aged over 75.

Risk factors

• There is a significant rise in the number of people with Alzheimer’s disease over the age of 65 years. However, most people over 80 years stay mentally alert.
• Although the risk of developing Alzheimer’s increases with age, old age is not considered a cause of the disease.
• Mutations in a few genes have been identified that increase the risk of developing Alzheimer’s disease.
• The risk of developing Alzheimer’s can be attributed to environment and lifestyle. For example, obesity has been linked to an increased risk of Alzheimer’s disease, while people who regularly engage in intellectual activities show a reduced risk of developing the disease.
• Some evidence suggests that a severe blow to the head can trigger Alzheimer’s. This risk is increased if:
  • the injury happens to an individual over the age of 50
  • the individual has a specific gene, called apolipoprotein E (ApoE) e4
  • the individual loses consciousness just after the injury.

Genetics

• Alzheimer’s disease has been found to run in families. Individuals who have a parent, brother, sister or child with Alzheimer’s are two to three times more likely to develop the disease.
• The genes involved in Alzheimer’s fall into two categories:

1. Risk genes

• These genes increase the likelihood of developing a disease.
  • The e4 form of the apolipoprotein E (ApoE) gene, on chromosome 19, increases the risk of an individual developing Alzheimer’s, although how that happens is not yet understood.
  • ApoE doesn’t definitively cause Alzheimer’s. Some individuals with the ApoE-e4 variant never develop the disease, and some people with Alzheimer’s do not have the ApoE-e4 variant.
  • ApoE-e4 is present in about 25 to 30 per cent of the population, and in about 40 per cent of those who develop Alzheimer’s after the age of 60.

2. Deterministic genes

• These genes directly cause the disease.
  • In a very small number of families, the disease is a dominant genetic disorder. In this case only one copy of the gene needs to be mutated for Alzheimer’s to occur.
  • Three genes have been identified that, if mutated, cause Alzheimer’s. These genes code for the amyloid precursor protein (APP), presenilin-1 (PS-1) and presenilin-2 (PS-2).

• The age of onset in families with a history of Alzheimer’s is relatively low, usually between 35 and 60 years.

Symptoms

• Symptoms normally develop after the age of 60 years but in some cases as early as 30s or 40s.
• There are three broad stages of Alzheimer’s:
  • Patient becomes increasingly forgetful: Although, this is also a feature of normal ageing and not, by itself, evidence of Alzheimer’s.
  • Forgetfulness becomes severe memory loss: Often memory of recent events or events of personal significance become lost. This is partnered with:
    • a decline in concentration and numerical ability
    • an inability to find the right word (dysphasia)
    • anxiety
    • unpredictable mood changes
    • personality changes.
  • Patients become severely disoriented and confused:
    • ​They may also suffer from:
      • delusions.
      • hallucinations.
    • They may become:
      • demanding and aggressive
      • docile and helpless.
• Alzheimer’s causes tangles to form in the brain made from a protein called tau. These tangles kill the nerve cells in the brain causing it to shrink.
• Levels of the neurotransmitter acetylcholine are much lower in the brains of patients with Alzheimer’s. The lower the levels, the more tangles form and the faster the brain shrinks.

Diagnosis

• A series of tests are used to determine if someone has Alzheimer’s.
• Tests of mental state can indicate decreased intellectual ability.
• Brain imaging, using computer tomography (CT) scanning or magnetic resonance imaging (MRI), can indicate a reduction in the size of the brain.
• The only way to diagnose Alzheimer’s definitively is after death, where post-mortem can reveal the characteristic deposits and tangles in the brain.

Treatment

• Currently there are no treatments that can reverse the memory loss associated with Alzheimer’s disease.
• Current drugs preserve the levels of acetylcholine in the brain to help maintain memory and concentration. In most patients the effects only last a few months and do not alter the steady decline associated with Alzheimer’s.