Alzheimers disease

Alzheimer’s disease (AD) is a degenerative brain disease, and those affected are normally over 65 years old. It is important for medics to understand AD because as life expectancy increases, cases of Alzheimer’s are also expected to rise, with huge financial and emotional cost to families, carers and the NHS.

AD is the leading cause of dementia, and as of 2013, there were 815,827 people suffering from dementia in the UK, which is about 1 in every 79 people (1.3%) in the population and 1 in every 14 people over 65. This number is steadily rising, and is expected to increase to >2,000,000 people by 2051 1. Because patients with Alzheimer’s usually need full-time care, especially as the disease progresses, many healthcare professionals are concerned about the future challenges of caring for so many people with the disease.

Signs and Symptoms

Overall the symptoms of AD are caused by damage to, and the death of, neurons (brain cells). The main features of this type of dementia are memory impairment, loss of language skills, impaired movement, changed sleep patterns, loss of organisation and planning, personality changes, a failure to recognise people or objects and little or no understanding of their difficulties and illness (a lack of insight). These symptoms are progressive, and so they worsen over time. Other reported symptoms or signs may include increased agitation and mood disturbances (e.g. depression).

Figure 1: the main signs and symptoms of AD

Later features can include wandering and becoming easily lost in their surroundings, even in places they used to know well, as well as behavioural changes (such as aggression), hallucinations or delusions 2. These later symptoms can make caring for these patients very hard, and families can struggle without support. Even caring for AD patients in care homes can be challenging, so healthcare staff need to be well trained to deal with symptoms like aggression, wandering and confusion.


AD is caused by the build-up of a protein called ‘beta-amyloid peptide’ in certain areas of the brain, and the build-up of another protein, ‘hyperphosphorylated tau protein’, which forms tangles within neurons. Beta-amyloid is a by-product of a cell membrane protein called Amyloid Precursor Protein (APP).

Enzymes cleave (cut) APP into the smaller beta-amyloid peptide, and as these proteins build up in the brain they cause progressive damage to the neurons and ultimately cause them to undergo apoptosis (cell death). The beta-amyloid peptides form aggregations or plaques around the neurons, affecting cell signalling and communication.

Figure 2: the enzymatic cleavage of APP into beta-amyloid peptide

The main neurotransmitter (cell signalling protein) that is reduced in Alzheimer’s disease is acetylcholine, a protein which is important for cell to cell communication, and the loss of acetylcholinergic neurons is a major cause of the symptoms of Alzheimer’s. The loss of neurons is higher in certain areas of the brain, with areas such as the hippocampus and amygdala (integral to memory) in the temporal lobe becoming severely affected, thus causing confusion and memory loss 3.

Figure 3 (left): a diagrammatic representation of the main brain areas affected in Alzheimer’s disease, and the subsequent cognitive functions affected 4

Figure 4 (right): a diagram showing a normal brain section and a section from a brain affected by Alzheimer’s disease. Note the overall loss of neurons (particularly grey matter) and shrinkage of the brain tissue 5

Risk Factors for AD

It is not known exactly why beta-amyloid builds up and causes AD, but research has revealed that there are certain risk factors which increase the risk of a person developing the disease. Risk factors are usually classified as environmental or genetic. Environmental risk factors are events that happen in a person’s life which are not determined by genetics – like injuries, certain diseases or habits. The main risk factors of AD are shown in figure 5. Sadly, another risk factor is loneliness, a condition that is all too prevalent in our society, especially amongst the elderly.

Figure 5: Genetic and environmental risk factors of Alzheimer’s disease

Genetic risk factors for AD have been found due to research into disease concordance (how often a disease occurs in both twins) in twins and family members; having a family history of Alzheimer’s is an important risk factor for developing the disease, and so far twin studies show about 40% concordance between identical twins. This means that in twins where one twin has Alzheimer’s, 40% of the second twins also have the disease 8.

Additionally, having a 1st-degree relative (a parent, sibling or child) with Alzheimer’s causes a doubled lifetime risk of the disease 2. This suggests that genetic mutations may play a key role in the development of AD.

However, most of these genetic mutations are different between families, and many have not yet been mapped to a certain part of the genome. The gene mutations that have been identified as a strong cause of familial AD are very rare, and they tend to cause early-onset Alzheimer’s (onset before 65). Because of this, the following gene mutations only cause about 1% of Alzheimer’s cases, but it is important to be aware of them and to diagnose them in those that carry them.

There are 3 identified gene mutations that have been strongly linked with early-onset AD:

  • Amyloid Precursor Protein (APP) – a point mutation on the APP gene on chromosome 21. This causes a larger amount of beta-amyloid peptide to be produced, resulting in beta-amyloid plaques forming relatively early. As a side note, this gene is the reason that people with Down Syndrome suffer from early-onset AD; as they have 3 copies of chromosome 21, rather than the normal 2, they produce larger amounts of beta-amyloid and develop amyloid plaques earlier 9.
  • Presenilin-1 and 2 (PS1 and PS2) – mutations in these genes alter the function of an enzyme that cleaves APP. These mutations cause these enzymes to cleave APP in a way that produces the pathogenic (disease causing) form of beta-amyloid, which then aggregates at a greater rate 9.


Diagnosing Alzheimer’s disease can be difficult in the early stages, but it is important to take a good history from the patient and someone who knows the patient well. A medical history includes asking about any present symptoms, a past medical history to learn about any other illnesses the patient may have had, a drug history to find out what medications the patient is taking or has taken in the past, and a social history so it is known whether they live alone or with others and whether they smoke or drink, among other questions.

An AD history may reveal that the patient is experiencing memory loss or forgetting information more easily than they used to. Relatives and friends may have noticed these changes more than the patient, as sometimes the affected person may normalise their symptoms and attribute them to ageing. Depression is common in dementia sufferers, and this must also be managed along with the dementia to increase the patient’s quality of life 10.

One screening tool for AD, (or the earlier, less serious state of mild cognitive impairment), is the Mini-Mental State Examination (MMSE). MMSE’s are tests that medical students and doctors perform regularly with patients who report problems with memory or mental ability. It is a series of questions and small tests, including numerical tests, questions about the patient’s history and general knowledge questions which help to gauge the patient’s cognitive state and test their memory, attention and language skills.

The MMSE flags up short or long term memory problems in a patient, and complements the history, symptoms and physical examination to help correctly diagnose mild cognitive impairment and AD 11. The symptoms of AD are on a spectrum, so patients with early AD may still be able to answer most of the questions on the MMSE, whilst those with more progressive disease may not be able to recall their own name or age.

Management of AD

There is currently no cure for Alzheimer’s, and research into drugs targeting the formation of beta-amyloid plaques has proved disappointing. The main class of drugs given to AD sufferers to slow down their cognitive decline and improve symptoms are acetylcholinesterase (AChase) inhibitors. As stated before, the main type of neuron lost in AD is the acetylcholinergic neuron. AChase inhibitors counteract this reduction in acetylcholine by inhibiting the AChase enzymes that normally break it down, leaving the small amount of acetylcholine still being produced to work for longer in the synapse.

Some examples of AChase inhibitors include the drugs donepezil, rivastigmine and galantamine, and these are either given orally, or can be given as a patch in the case of rivastigmine. Unfortunately all drugs have side-effects, and AChase inhibitors can cause diarrhoea and vomiting, headaches, dizziness, incontinence (cannot hold urine/faeces), insomnia, heart rhythm problems and stomach ulcers 12.

Research has also shown that some benefit may be seen by targeting another neurotransmitter called glutamate, but in this case the aim is to inhibit its actions. As acetylcholine production reduces in AD, glutamate synthesis increases in compensation, and this can worsen the symptoms. Antiglutamatergic drugs such as memantine have been found to be reasonably effective at helping control symptoms in late-stage AD. However, the side-effects can include confusion and hallucinations, so patients on any AD drugs should be carefully followed-up by their doctor and have regular medication reviews 12.


There is some evidence that certain lifestyle choices can be protective against the development of AD; for example, those who take part in intellectual activities throughout their life, such as playing a musical instrument, playing chess or learning another language have a reduced risk of the disease. Keeping physically active also reduces that person’s risk 13.

A healthy diet seems to play a role too; a Mediterranean diet, including small amounts of red meat and lots of grains, vegetables, fish, nuts and olive oil seems to be protective. Lowering the intake of sugar, saturated fats, processed meat and alcohol in the diet can reduce the risk of developing AD in the future, as well as having many other health benefits too, so this advice should be given to all patients, regardless of age 14.


AD is a progressive illness, and the disease progresses quicker is some and slower in others. As with all illnesses and diseases, different people cope in different ways, and it may be that some people cope better than others with their symptoms. However, overall the average life expectancy after diagnosis is only 6 years, with few surviving more than 14 years 15. The burden on carers and the health service increases with time as the patient becomes more dependent and less able to look after themselves. Falls and injuries further complicate their management, and eventually they become bed-ridden and completely dependent on others. Sadly the ultimate cause of death is often pneumonia (associated with swallowing problems and the aspiration (breathing in) of food into the lungs) along with dehydration 15.

The expected rapid increase in AD cases over the next few decades is concerning; in 2003, the estimated global cost of treating and caring for dementia patients was about $160 billion 16. One very important aspect to remember is the carers who look after AD sufferers in their homes; carers often spend a lot of their own money caring for the individual, and sometimes find that they have to resign from their jobs to be full-time carers, resulting in the loss of their own income. They are a very important link between AD patients and health services, and because of this they need support and help from services and charities. Unfortunately they do not always get the amount of support that they need, and many struggle to care for their family member or loved one. Better carer support systems are called for to improve this situation.


AD is a progressive, degenerative brain disease, and the number of cases are rising rapidly along with life expectancy. It is our duty as medical students and future health care professionals to understand AD and the social issues underlying the disease in order to not only support and help the patient during the disease course, but also to support the family as well.


  1. Alzheimer’s Society, Demography, Online at Accessed: 26/06/15
  2. Kumar P, Clark M. Kumar & Clark’s Clinical Medicine, 8th Edition. Saunders Elsevier, 2012, pp. 1138-1139
  3. Longmore M, Wilkinson IB, Baldwin A, Wallin E. Oxford Handbook of Clinical Medicine, 9th Edition. Oxford University Press, 2014, pp. 492
  4. Brain Areas Affected Diagram, Accessed: 01/07/15
  5. Diagram Comparing Normal and Diseased Brain, Accessed: 01/07/15
  6. Alzheimer’s Society, Risk Factors Accessed: 02/07/15
  7. Kumar P, Clark M. Kumar & Clark’s Clinical Medicine, 8th Edition. Saunders Elsevier, 2012, pp. 1140
  8. Epidemiology of Dementia Twin Studies Accessed: 02/07/15
  9. Kumar P, Clark M. Kumar & Clark’s Clinical Medicine, 8th Edition. Saunders Elsevier, 2012, pp. 1139-1140
  10. Longmore M, Wilkinson IB, Baldwin A, Wallin E. Oxford Handbook of Clinical Medicine, 9th Edition. Oxford University Press, 2014, pp. 490
  11. The Mini Mental State Examination
    Accessed: 09/07/15
  12. Longmore M, Wilkinson IB, Baldwin A, Wallin E. Oxford Handbook of Clinical Medicine, 9th Edition. Oxford University Press, 2014, pp. 493
  13. Stern, Y. (2006). Cognitive reserve and Alzheimer disease. Alzheimer Disease & Associated Disorders, 20(2), 112-117.
  14. Prevention and Risk of Alzheimer’s and Dementia Accessed: 09/07/15
  15. Mölsä, P. K., Marttila, R. J., & Rinne, U. K. (1986). Survival and cause of death in Alzheimer’s disease and multi‐infarct dementia. Acta Neurologica Scandinavica, 74(2), 103-107.
  16. Wimo, A., Jonsson, L., & Winblad, B. (2006). An estimate of the worldwide prevalence and direct costs of dementia in 2003. Dementia and geriatric cognitive disorders, 21(3), 175-181.

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