Updated 04 May 2018

Causes of dementia

The most common cause of dementia in older adults is Alzheimer's disease. The exact cause of Alzheimer's disease is unknown.

The most common cause of dementia in older adults is Alzheimer's disease. A German doctor in 1906, Dr Alois Alzheimer, first described the disease. He described characteristic changes in the brain tissue of a woman who had died of an unusual mental illness.

Today still, the exact cause of Alzheimer's disease is unknown. However, we know much more about what happens in the brain and a number of risk factors for the illness have also been identified. The disease process causes structural changes of brain matter and, associated with this, certain brain chemicals (neurotransmitters) also change.

In Alzheimer's disease the disease process starts in the temporal lobes and from there it spreads to involve other brain areas. The areas involved in basic processing of sensory and motor functions are usually spared, as well as some of the nuclei in the deep brain matter. The cerebellum (or small brain) is also comparatively spared.

Brain structure is disrupted by the formation of neurofibrillary tangles (NFT) and neuritic plaques (NP). Formation of NFT and NP causes disruption of the integrity of brain cells and leads to brain cell death.

The loss of brain cells leads to neurotransmitter deficits, especially the loss of acetylcholine (ACh). Medication that increases the level of ACh in the brain leads to an improvement of memory in Alzheimer's disease.

Risk factors
The most important risk factor for the development of Alzheimer's disease is old age. The illness usually begins after age 55 and the disease doubles every five years beyond age 65. Approximately 8 to 10% of all persons older than 65 have Alzheimer's disease and nearly 30 to 50% of persons older than 85 have the disease.

Women are at slightly increased risk of developing Alzheimer's disease compared with men (1.2 to 1).

Genetic factors also contribute to the risk for developing AD. The risk for developing the illness increases 2 to 3 fold having one close relative with AD. A specific gene on chromosome 19 called apolipoprotein-E has been identified as a susceptibility marker. APOE has three forms and it is the presence of the APOE-4 form that is associated with an increased risk for the development of AD. Not all people with APOE-4 develop AD and not all people with AD carry this gene. Routine testing for this gene is not recommended by Memory Clinics.

Another and very rare form of genetic inheritance is associated with mutations on specific chromosomes. This form of inheritance occurs in less than 2% of all people with AD and both the Panorama Memory Clinic and Tygerberg Hospital Memory Clinic are not aware of any such cases in the Western Cape. This inheritance pattern is associated with the development of AD in every generation. It also tends to develop at an earlier age.

A history of severe head injury (loss of consciousness of 1 hour or more) is associated with an increased risk for AD. This risk increases with the presence of the APOE-4 gene.

Protective factors
A number of protective factors have been identified. Higher education levels are associated with lower rates of AD. Long-term use of anti-inflammatory agents is associated with a decreased rate of the illness. The same has been described in postmenopausal women who use oestrogen in the form of hormone replacement therapy.

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