Biological risk factors
Prevention of dementia
Age is the most important known risk factor for AD. The risk of developing the disease doubles every five years over age 65. Dementia may occur at any age, although rarely below the age of 60. Although age is the most significant risk factor that we know about, dementia is not an inevitable part of ageing.
Family history of dementia
Some genetic risk factors have been identified so far, but only a small proportion of AD cases can be explained by specific gene mutations. The risk of dementia and AD has been shown to be increased among people with a family history of dementia, but contradictory results exist as well.Life table analyses have shown a cumulative risk of dementia to first-degree relatives of AD cases of approximately 50% by age 90, while relatives of purported control subjects had a much lower cumulative risk. Studies of AD among twin pairs over age 70 provide the strongest support for genetic causation. Monozygotic twin pairs show higher concordance rates for AD than dizygotic twin pairs
Genes may be related to disease in two ways: through autosomal-dominant mutations, in themselves sufficient to cause the disease alternatively, gene variations (polymorphisms) may indirectly increase disease risk without being sufficient in themselves to cause the disorder. This latter group are referred to as susceptibility genes. Familial AD refers to small numbers of cases (at least 5% of all cases), in which there is a clear pattern of autosomal dominant inheritance. Such clear patterns usually are associated with an age of onset before 60 years of age. The disease usually starts in the 40’s and 50’s. These mutations have principally concerned early onset AD, and only explain a small proportion (less than 1%) of total cases Some susceptibility genes are also currently being studied, of which polymorphisms of the apolipoprotein E gene have received the most attention, with earliest clinical reports suggesting it to be present in about 90% of late onset cases (which occur predominantly after 60 years old and do not have an apparent autosomal dominant mode of inheritance). Meta-analysis of recent epidemiological studies has shown that while ApoE e4 is more common in all forms of AD than in controls, it is specifically related to the late onset rather than the early onset variant. ApoE e4 is thus seen to be mostly strongly associated with late onset familial cases of AD. Having one copy of the ApoE e4 gene increases a person’s risk of developing AD by up to four times. Someone with two copies of ApoE e4, one from each parent, has a 10 times greater risk and earlier age of onset than individuals who inherited one e4 allele, but only about 2% of the population have two copies of e4. The most common form of the gene is e3. About 60% of the population have two copies of ApoE e3 and are at average risk, which, means that about half will develop the disease by their late 80s. About one in six people has at least one copy of ApoE e2. This form of the gene delays the onset and decreases the risk of AD. The lowest risk is for people who have two copies of ApoE e2. It is important to recognise that this gene affects risk and is not a predictor of whether someone will develop AD. Although ApoE e4 increases the risk of developing the disease it does not make it certain. Many people who develop AD do not have an ApoE e4 gene, and some with the e4 type do not develop the disease. It is now recognized that ApoE is not the ‘cause’ of AD, but rather an important link in a biological chain of events, AD itself appearing less like a single disease process and more the result of the failure of diverse neuronal compensatory and repair mechanisms to deal with multiple ageing-related aggressions. An interactive effect with ApoE in AD has now been demonstrated in relation to a number of other risk factors so that the ApoE e4 carriers might be more vulnerable to various adverse environmental factors e.g. physical inactivity, saturated fat intake, alcohol drinking, diabetes, high BP and low B12/folate.
It has been suggested that the prevalence of AD is higher in women than in men. It is not clear whether this difference is due to biology, to the fact that women tend to live longer or to their behaviour On the other hand, studies from provide evidence against a sex difference in the risk of AD. Vascular dementia is more common in men than women across all age groups. This may be because risk factors for vascular dementia, such as high blood pressure and heart disease, are more common in men. Overall, 66% of people with dementia are female. However, the proportion varies with age group: women account for only 37% of people with dementia between 65 and 69, but 79% of people with dementia aged 90 and above.
Last Updated: Thursday 08 October 2009