Revised: May 2021 First published: December 2014
Alzheimer’s disease (AD) is the most common form of dementia affecting the elderly population in the UK, accounting for approximately 50% of all dementia diagnoses.1 Currently the aetiology is unknown. AD is a progressive neurodegenerative disease that is associated with atrophy and loss of function of cortical neurons in the brain. Two abnormal structures can be seen in the brains of those with AD—amyloid plaques and neurofibrillary tangles. AD is also associated with reduced production of acetylcholine, which is a key neurotransmitter in the cholinergic system of the brain.2,3
Acetylecholinesterase inhibitors are the mainstay of pharmacological management and a multidisciplinary team is essential for the long-term management of symptoms. The multidisciplinary team involves, doctors, nurses, occupational and physiotherapists, social workers, dietitians and all other specialties involved in the patient’s care.
Progression will eventually lead to death, commonly from bronchopneumonia or ischaemic heart disease. The current aims of AD societies are to increase public awareness and understanding of the disease.
Diagnosis of Alzheimer's disease
First and foremost, Alzheimer’s or any subtype of dementia is not a part of normal ageing. AD results in a progressive degeneration of brain function. Initial symptoms commonly involve problems with memory, particularly short- term memory. There are four main categories of symptoms in dementia: cognitive, behavioural and psychiatric symptoms, functional impairment and personality change.
The American Alzheimer’s Association have a useful 10 step warning sign resource for AD) The presence of these initial warning signs can suggest further testing is needed to rule out or diagnose dementia.4
As the condition progresses the clinical signs and symptoms worsen, resulting in someone with AD becoming dependant on care. This stage is defined as advanced dementia.
The list of potential differential diagnoses can be split into reversible and irreversible causes. It is important to rule out the reversible causes before making a diagnosis of AD. Reversible causes include: acute confusional state—which could be due to underlying illness or infection, hypothyroidism, vitamin B12 deficiency, depression, drug induced cognitive impairment and normal pressure hydrocephalus. Forms of irreversible causes may include normal ageing, other subtypes of dementia, and Parkinson’s disease.2
There are subtle differences between the different types of dementia as well as overlaps in symptoms with other reversible conditions (as listed above); therefore it is important to rule out differential diagnoses. Screening blood tests for reversible causes should be performed including full blood count, urea and electrodes, liver function tests, erythrocyte sedimentation rate/c-reactive protein, glucose, calcium, thyroid function tests, B12 and red cell folate.2,5
It is not routine practice to screen for syphilis or HIV unless clinically indicated. A urinalysis may be performed if delirium is suspected. Cerebrospinal fluid examination may be undertaken if Creutzfeldt–Jakob disease or other forms of rapidly progressive dementia are suspected.5
Early in 2014 a study by Lovestone et al identified 10 plasma proteins that were strongly associated with the progression from mild cognitive impairment to AD and its severity. The study suggests that early blood tests to identify these 10 specific plasma proteins could have the potential to be used as a triaging system in patients with early memory disorders, to prompt further invasive investigation.6 As always, a full history and physical examination needs to be performed, as well as a review of medications that could impair cognition. A cognitive and mental state examination is also necessary.l
A formal cognitive assessment can be performed using one of the following: Mini Mental State Examination (MMSE), 6-Item Cognitive Impairment Test (6-CIT), General Practitioner Assessment of Cognition (GPCOG), or 7-Minute Screen.5 Once a diagnosis of dementia is made, the next step is to differentiate the subtype of dementia the patient has. If an Alzheimer’s form is suspected then diagnostic criteria can be used to confirm suspicions.7 The two most commonly used diagnostic criteria for Alzheimer’s disease are documented in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV); as well those devised by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association (NINCDS ADRDA)—which NICE currently recommends to use.1,2,8 The severity of AD can be quantified by the Mini Mental State Examination (MMSE).
Structural imaging, most preferably MRI can be used to exclude other cerebral pathologies. Perfusion hexamethylpropyleneamine oxime (HMPAO) single-photon emission computed tomography (SPECT) can be used to help differentiate between AD, vascular dementia and frontotemporal dementia.5
Management of Alzheimer's disease
Currently there is no cure for AD and the aim of management is to provide symptom control. There are both pharmacological and non-pharmacological treatments available for this.
Acetylcholinesterase (AChE) inhibitors are the mainstay of pharmacological management of AD.9 This is based on the ‘cholinergic hypothesis’, which suggests that cholinergic pathways in the cerebral cortex and basal forebrain are compromised in AD and the resulting deficit contributes to cognitive impairment.10
All management should only be initiated by specialists in dementia and should be considered in those with mild to moderate AD. It is recommended to initiate AChE inhibitor therapy as early in diagnosis as possible. The initial drug choice within this group should be based on lowest cost. Due to cholinergic side effects, drug therapy should be started at a low dose and titrated up according to response and tolerability. Pharmacological treatment should be regularly reviewed after three months to ensure continuing response.2,5 Up to half of patients treated with AChE inhibitors will show a slower rate of cognitive decline.11
As with all drug therapies, AChE inhibitors are not without their side effects. The majority of these are due to peripheral cholinergic effects—commonly gastrointestinal effects such as nausea, diarrhoea and vomiting.10 Each individual drug has a side effect profile to be aware of and to consider before initiating treatment. AChE inhibitors are available in a variety of forms other than tablets, such as oral solutions, patches, and orodispersible tablets, which is useful particularly in AD progression as difficulties in swallowing often can develop.11,12
Approximately 30–40% of patients do not respond to AChe inhibitor therapy, therefore once the maximum tolerated dose has been reached without effect, it is recommended that the drug is withdrawn.10 In this case it would be beneficial to explore the non-pharmacological treatment options for AD.
Memantine is a glutamate receptor antagonist licensed for treating moderate to severe AD or in those who cannot tolerate AChE inhibitors. Current guidelines do not recommend combination treatment of memantine and AChE inhibitors.11 Memantine is also available as an oral solution.12 Management of AD also includes the control of symptoms such as dysphagia, depression, decrease in mobility, anxiety, aggression, and incontinence. The role of the multidisciplinary team is essential in managing these symptoms.
Non-pharmacological treatment aims at managing the social impact AD has on the individual and the community around them. It involves reviewing how AD effects their daily lives and providing assistance where needed. This includes: social support, information and education, carer support, respite, community dementia teams and care homes.12 In a July 2014 press release NICE stated it was currently working on a guideline named ‘Disability, dementia and frailty in later life—mid-life approaches to prevention’, which could be the start of practical advice to prevent the development of dementia.13
Prognosis of patients diagnosis with Alzheimer's disease
Statistics show that 60–70% of patients respond to medical therapy, however this can only slow the progression of the disease, not cure it. Ultimately all patients with dementia will decline. The median survival for people with Alzheimer’s disease from onset is approximately seven years.12 In the UK approximately 60,000 deaths/annum are due to dementia. An analysis of death certificates from 2001–2009 in England showed that dementia or frailty was a cause or contributed to 15% of deaths.14 The two most common causes of death in patient with AD are bronchopneumonia and ischaemic heart disease.15 In the latter stages of dementia often patients find it difficult to feed themselves adequately and also their swallowing abilities may be decreased, leading to a higher rate of aspiration of food-stuff, which develops into pneumonia.
Dementia typically affects the elderly population, where an element of atherosclerosis in major blood vessels—including the heart has already had time to develop. Also risk factors for developing Alzheimer’s disease include those relating to vascular disease such as high cholesterol, hypertension and diabetes. Therefore those with Alzheimer’s disease have a higher likelihood of dying from ischaemic heart disease due to those comorbidities.
Due to the progressive nature of this disease, it is important to consider a palliative care approach in these patients, in order to preserve their quality of life and dignity in death.16
Further care for Alzheimer's disease
Baseline laboratory tests should be carried out in primary care and more specialist assessment should be conducted in a more specialist environment, such as a memory assessment clinic or within community mental health teams.5 This ensures that effective multidisciplinary team management is used in the management of AD.
The main charitable group for AD is the Alzheimer’s Society, which provides information, advice, and research and promotes fundraising for Alzheimer’s disease. Their website has a section to help people discover what support is available in each region in the UK, as well as a publication section that provides further information. This website also provides the National Dementia Helpline that helps provide information, support and guidance. Calls are from those who have dementia, or who are worried about developing dementia, carers of those with dementia or people looking for more information.17
The Alzheimer’s Society and Public Health England have also come together to create a scheme called the ‘Dementia Friend Campaign’. The main aim is to increase awareness and understanding of dementia in the community.18 The dementia guide on the nhs.uk website also provides further information on dementia.19
Dementia awareness week was on the 18–24th of May 2014, based on the slogans ‘Don’t bottle it up’, ‘Don’t bury your head in the sand’ and ‘Don’t brush it under the carpet’; aiming to raise awareness of dementia in the UK. World Alzheimer’s month is a global initiative to again increase awareness and understanding around AD.20
The prevalence and impact this disease has on our society reinforces how important raising awareness of AD is, so that people can recognise the signs and symptoms in order to be diagnosed earlier and are knowledgeable on the services available to help during the progression of this disease.
For more news and articles on Alzheimer's disease visit our neurology section
Dr Zosia Vanessa Beckett is CMT2 in the West Yorkshire Region
Conflict of interest: none declared
- NICE. Dementia clinical topic summary. 2010. http://cks.nice.org.uk/dementia (accessed 27/11/14)
- Harding M. Alzheimer’s disease - professional reference. Patient.co.uk. [Online] [Cited: 16 09 2014.] www.patient.co.uk/doctor/alzheimers-disease (accessed 10/12/14)
- Lillrank S. Collins C, Levitt P. Alzheimer’s disease and other dementias. s.l: Infobase Publishing, 2007
- Alzheimer’s Association. Know the ten signs. Alz.org. [Online] 2009. www.alz.org/national/documents/checklist_10signs.pdf. (accessed 10/12/14)
- NICE. Dementia diagnosis and assessment. National Institute for Health and Care Excellence . [Online] 2014. http://pathways.nice.org.uk/pathways/dementia (accessed 27/11/14)
- Lovestone et al. Plasma proteins predict conversion to dementia from prodromal disease. Alzheimer’s and Dementia 2014; 10(6): 799–807
- Phelps et al. The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute of Aging and Alzheimer’s Association workgroup. 2011, Alzheimer’s and dementia
- Anderson H. Alzheimer Disease. Medscape. [Online] 2014. http://emedicine.medscape.com/article/1134817-overview (accessed 27/11/14)
- NICE. Alzheimer’s disease (mild to moderate) - donepezil, rivastigmine and galantamine. NICE guidance. 2001. http://www.nice.org.uk/guidance/ta19 (accessed 10/12/14)
- McGleenon B. Dynan K. Passmore A. Acetylcholinesterase inhibitors in Alzheimer’s disease. British Journal of Clinical Pharmacology 1999; 48
- British National Formulary. s.l: BMJ Group, Pharmaceutical Press, 2014
- NICE guidance. Donepezil, galantamine, rivastigmine and memantine for the treatment of alzheimer’s disease. 2011. http://www.nice.org.uk/guidance/ta217 (accessed 10/12/14)
- NICE draft guideline, Dementia, disability and frailty in later life – mid-life approaches to prevention. Due 2015. https://www.nice.org.uk/guidance/indevelopment/gid-phg64 (accessed 10/12/14)
- Aquilina C, Crugel M, Dives T, et al. Thompsell A. Dementia: From Advanced disease to bereavement. 2011.
- Brunnström HR, Englund EM. Cause of death in patients with dementia disorders. European Journal of Neurology 2009: 16(4)
- NICE. Dementia overview - pathway. 2006
- Alzheimer’s Society. [Online] http://alzheimers.org.uk/site/index.php. (accessed 10/12/14)
- Alzheimer’s society and Public Health England. Dementia Friends. [Online] www.dementiafriends.org.uk/ (accessed 10/12/14)
- Dementia Guide. NHS Choices. [Online] www.nhs.uk/Conditions/dementia-guide/Pages/about-dementia.aspx (accessed 10/12/14)
- World Alzheimer’s Month. Alzheimer’s Disease International. [Online] www.alz.co.uk/world-alzheimers-month (accessed 10/12/14)