Many factors are known to contribute to the risk of developing Alzheimer's disease, the most well known of these being age. New areas of research point to possible preventable risk factors such as hypertension and diabetes.
Factors Known to Contribute to the Development of Alzheimers disease
Age
The incidence of Alzheimers undoubtedly increases with age, doubling every five years from 1% in the sixties to reach 32% of the population by the age of eighty-five.
Normal ageing is associated with altered protein metabolism. This leads to the formation of the senile plaques and neurofibrillary tangles that are characteristic of the disease, meaning more degradation of neuronal cells with every increasing year.
Age is not the only consideration, however. Some people are more prone to production of the senile plaques and neurofibrillary tangles for other reasons, giving these age-related changes a much bigger impact and making the development of the disease much more likely.
Family History / Genetics
Early onset of the condition, also known as Familial Alzheimers Disease (FAD) only accounts for 1% of all cases, and is linked to mutations on either chromosome 1, 14, or more commonly 21. People with 2 or more generations of first-degree relatives who have suffered from the disease are considerably more likely to develop Alzheimer's themselves than people with no family history. Family history of Parkinsons disease and depression also appear to have a bearing on development, possibly connected to altered brain chemistry.
The genetic component of the risk of late onset Alzheimers is highly significant. There are two main genes whose presence has an effect on the incidence of the disease.
ApoE4
The gene for Apolipoprotein E is found on chromosome 19. There are several forms (e.g. ApoE2, ApoE3), most of which are clinically harmless.
People with one or both copies of the gene coding for type ApoE4 are more likely to develop the disease earlier in life - a prevalence of 30-40%, compared with 15-20% in older people whose genes are both type ApoE2, who appear to be protected against the disease for longer.
This is because ApoE interacts with beta-amyloid protein, each type having a slightly different action. ApoE4 promotes its aggregation to form senile plaques while ApoE2 does not, meaning that plaques will develop at a slower rate.
APP / Downs Syndrome
The gene for Amyloid Precursor Protein (APP) is on chromosome 21. It is this protein that is cleaved to form beta-amyloid peptide, which then clumps to form senile plaques. Increased levels of APP therefore contribute to the risk of developing Alzheimers disease. People with Downs Syndrome are particularly prone, the majority of those who reach the age of 40 being affected.
The above are known risk factors, but there are many more under investigation, which may lead to other dementias rather than Alzheimers itself.
Probable Causes
Gender
Studies have shown that women have a slightly higher risk of developing Alzheimers than men of the same age, even when relative survival rates are accounted for. Scientists are not yet sure why this is, but it appears that it could be linked to the higher incidence of the ApoE4 gene mentioned above, but a role for oestrogen is also being investigated.
Low Level of Education
Several studies have recently indicated that a higher level of education may offer protection, though it is not clear as yet whether this is a direct effect or whether some other related factor such as natural intelligence or income level is responsible. It does, however, offer hope that keeping mentally active may help ward off the disease.
Possible Causes
These are related to situations or conditions that cause damage in the brain. People who have previously suffered a sustained head injury have a small but significantly increased risk of developing Alzheimers.
Other possible causes include diseases such as diabetes mellitus and thyroid disorders, and conditions liable to cause vascular problems in the brain, such as high blood pressure (hypertension) or heart attacks. Exposure to toxins like aluminium, solvents and alcohol are also thought to be injurious.
03/06/2009