Alzheimer's Disease

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What is it?

Alzheimer's Disease (AD) is an irreversible form of dementia characterised by memory loss, a progressive decline in intellectual ability, deteriorating language and speech skills, and by personality and behavioural changes that eventually interfere with daily living. The commonest early sign is memory loss, especially for recent events. Long term memory is often preserved in the early stages of AD. Patients find it difficult to multi-task and may have disturbed sleep patterns, being wakeful during the night.

According to the Alzheimer's Society, the number of people living with dementia in the UK is about 850,000, 1.3% of the population, and it predicts that this will grow to over a million by 2025. Approximately 62% of people with dementia have Alzheimer’s disease which is the most common form of dementia. Although AD mimics some changes found in the brain as we age, it is not a normal part of the aging process. It causes nerve cell injury and death and is characterised by the build-up of senile plaques and neurofibrillary tangles (twisted protein fragments that clog nerve cells) in the brain. The destruction of nerve cells also decreases levels of acetylcholine and other neurotransmitters (chemicals necessary for communication between nerve cells) in the brain. Over time, AD results in decreased interaction between different areas of the brain. Although AD mimics some changes found in the brain as we age, it is not a normal part of the aging process. It causes nerve cell injury and death and is characterized by the build-up of senile plaques and neurofibrillary tangles (twisted protein fragments that clog nerve cells) in the brain. The destruction of nerve cells also decreases levels of acetylcholine and other neurotransmitters (chemicals necessary for communication between nerve cells) in the brain. Over time, AD results in decreased interaction between different areas of the brain.

Relationship with Ageing
The risk of having AD and other dementias increases greatly with age. About 10% to 12% of the population will have dementia by the time they are 65 years old, with the risk increasing to 50% for those who reach the age of 100. Most of the time AD is “late onset,” beginning after the age of 65, and sporadic (does not seem to be family-related). "Early onset" AD, starting before the age of 65, is more rare and more likely to be family-related. (It accounts for about 5% to 10% of all AD cases).

Risk factors
The main risk factors for developing AD are age and a family history of dementia. Other factors such as smoking, obesity, high blood pressure, diabetes mellitus and dyslipidaemia (abnormal blood cholesterol or fats) are better known as risk factors for heart disease but are also associated with AD. Women are at higher risk than men. Exercise, social and mental stimulation, a moderate intake of alcohol and a Mediterranean type diet appear to be protective.

Genetic Relationship
Although we know that people with a family history of the condition are more likely to develop AD, the genetics of the common type of AD are not well understood.

We know that there are a few very rare cases, associated with early onset Alzheimer's disease, where there is a clear genetic inheritance within specific families. These are families where members inherit genetic faults on chromosomes 14, 1 or 21. The genes affect proteins in the brain called presenilin 1, presenilin 2 and amyloid precursor protein respectively. Children of affected individuals have a 50% chance of inheriting the condition. All those who inherit the gene will go on to develop Alzheimer's.

Another gene, ApoE, has been associated with an increased susceptibility to late onset AD. This gene directs the production of apolipoprotein E, a protein that forms part of the body’s lipoproteins (such as HDL cholesterol) and is involved in lipid transportation and clearing dietary fats from the body. The ApoE gene normally exists in three forms: e2, e3, and e4. Everyone has two copies of the ApoE gene, in some combination of the three forms. People who have two copies of the e4 variant have a fifteen fold increased risk of AD.

There is a higher incidence of Alzheimer’s Disease in people with Down's Syndrome and in families who have siblings and/or parents with AD and/or several generations of family members with AD. Researchers have been aware of a connection between Down's syndrome and Alzheimer's disease since the 1940s. People with Down's syndrome, who inherit an extra copy of chromosome 21, develop the same 'plaques' and 'tangles' in their brains as people with Alzheimer's disease.

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