Alzheimer's Disease

Authored by , Reviewed by Dr Laurence Knott | Last edited | Meets Patient’s editorial guidelines

This article is for Medical Professionals

Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find the Memory Loss and Dementia article more useful, or one of our other health articles.


Treatment of almost all medical conditions has been affected by the COVID-19 pandemic. NICE has issued rapid update guidelines in relation to many of these. This guidance is changing frequently. Please visit https://www.nice.org.uk/covid-19 to see if there is temporary guidance issued by NICE in relation to the management of this condition, which may vary from the information given below.

Alzheimer's disease (AD) is the most common cause of dementia, and involves a progressive degeneration of the cerebral cortex. There is widespread cortical atrophy. Neurons affected develop surrounding amyloid plaques, neurofibrillary tangles, and produce less acetylcholine. The cause is not yet known. Patients experience irreversible global, progressive impairment of brain function, leading to reduced intellectual ability.

Neurodegeneration in Alzheimer's disease probably begins at least a decade before clinical onset.

The prevalence of Alzheimer's and vascular dementia in specific age groups has decreased over the last 20 years, probably due to a reduction in vascular risk factors and better health education. However, with increasing life expectancy (ageing is the main risk factor for dementia), the overall number of people living with dementia is expected to continue rising.

  • Alzheimer's disease is the most common form of dementia. It is estimated to affect 520,000 people in the UK.
  • Dementia affects 7.1% of the population over the age of 65, and prevalence increases with age.
  • Sporadic Alzheimer's disease is very common with more than 15 million people affected worldwide. The cause of the sporadic form of the disease is unknown, probably because the disease is heterogeneous, caused by ageing along with a complex interaction of genetic and environmental risk factors.
  • Familial Alzheimer's disease is a very rare autosomal dominant disease with early onset[2].

Risk factors

Non-modifiable risk factors include:

  • Ageing.
  • Caucasian ethnicity.
  • Family history. Small increased risk - 3.5-fold increase if a first-degree family member is affected.
  • Apolipoprotein E4 variant - the largest known genetic risk factor in late-onset sporadic Alzheimer's disease, but wide differences in prevalence of the genotype in populations studied[3, 4].

A third of Alzheimer's disease cases are potentially attributable to modifiable risk factors. Modifiable risk factors for Alzheimer's disease are mostly related either to cardiovascular risk factors (diabetes, hypertension and obesity) or to lifestyle habits (eg, smoking, physical activity, diet, and mental and social activity)[5]:

  • The relationship between body weight and Alzheimer's disease seems to be a consequence of midlife obesity, which could increase the risk of Alzheimer's disease by 60%.
  • The association between smoking and Alzheimer's disease risk has been controversial and remains unclear.
  • Epidemiological studies have shown that physical activity has a beneficial effect on brain health. In comparison with sedentary behaviours, individuals with high levels of physical activity have been shown to reduce their Alzheimer's disease risk by half.
  • Cognitive, social and intellectual activity jointly with higher education and occupational attainment have been shown to decrease risk of cognitive decline and dementia by increasing cognitive reserve, the capacity of the brain to resist the effects of neuropathological damage.

The National Institute for Health and Care Excellence (NICE) guidelines recommend the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) diagnostic criteria be used for the assessment of Alzheimer's disease[6]. Alternatives are the ICD-10 or DSM-IV (now DSM-5 since the guidelines were written) criteria[7, 8].

The NINCDS/ADRDA criteria were proposed in 1984 and revised in 2011[9]. Core features for diagnosis of Alzheimer's disease include:

Probable Alzheimer's disease

  • Dementia established by clinical examination and neuropsychological tests.
  • Deficits in two or more areas of cognition.
  • Insidious onset over months to years, and progressive worsening of memory and other cognitive functions.
  • No disturbance of consciousness.
  • Onset between ages of 40 and 90. (Criterion removed in latest revision.)
  • Absence of systemic disorders or other brain diseases that could account for the symptoms. 

Possible Alzheimer's disease

  • Dementia with an atypical onset or course (ie sudden onset or insufficient documentation of progressive decline); OR
  • Aetiologically mixed presentation (ie other criteria fit the diagnosis, but features of other brain disorders or causes of dementia are present).

Mild cognitive impairment due to Alzheimer's disease

Newer diagnostic criteria have attempted to classify the symptomatic, pre-dementia stage of Alzheimer's disease. The work group which revised the NINCDS/ADRDA criteria in 2011 refers to this stage as 'mild cognitive impairment' with clinical diagnostic criteria as follows[10]:

  • Concern regarding a change in cognition (from patient, informer or clinician).
  • Impairment of one or more cognitive domains.
  • Preservation of independence in functional abilities.
  • Not having the features of dementia.

DSM-5 refers to this earlier stage as mild neurocognitive disorder (mild NCD) and there is ongoing debate in this area.

Onset of Alzheimer's disease is insidious, and it usually progresses slowly over 7-10 years.

Symptoms in early stages include:

  • Memory lapses.
  • Forgetting names of people and places.
  • Difficulty finding words for things.
  • Inability to remember recent events.
  • Forgetting appointments.

As the disease progresses, symptoms include:

  • Difficulties with language.
  • Apraxia.
  • Problems with planning and decision making.
  • Confusion.

In the later stages, symptoms include:

  • Wandering, disorientation.
  • Apathy.
  • Psychiatric symptoms - depression, hallucinations, delusions.
  • Behavioural problems - disinhibition, aggression, agitation.
  • Altered eating habits.
  • Incontinence.

Cognitive changes with ageing may be very difficult to distinguish in the mildly affected, early stages of Alzheimer's disease.

There are several tools available for screening for cognitive impairment, and other routine investigations are detailed in the separate Dementia article. MRI scans are the investigation of choice to exclude other cerebral pathology. To differentiate Alzheimer's disease from vascular dementia or frontotemporal dementia, NICE guidance advises perfusion hexamethylpropyleneamine oxime (HMPAO) single-photon emission computerised tomography (SPECT). This is not useful if the person has Down's syndrome.

Note that cognitive screening tests such as the mini mental state examination (MMSE) are not diagnostic of dementia. They are, however, useful screening tools to assess who should be referred to specialist services[1].

When using assessment scales to determine the severity of Alzheimer's disease, healthcare professionals should take into account any physical, sensory or learning disabilities, or communication difficulties that could affect the results, and make any adjustments they consider appropriate.

When assessing the severity of Alzheimer's disease and the need for treatment, healthcare professionals should not rely solely on cognition scores in circumstances in which it would be inappropriate to do so. These include:

  • The cognition score is not, or is not by itself, a clinically appropriate tool for assessing the severity of that patient's dementia because of the patient's learning difficulties or other disabilities, linguistic or other communication difficulties or level of education; or
  • If it is not possible to apply the tool in a language in which the patient is sufficiently fluent for it to be appropriate for assessing the severity of dementia; or
  • If there are other similar reasons why using a cognition score, or the score alone, would be inappropriate for assessing the severity of dementia.

In such cases healthcare professionals should determine the need for initiation or continuation of treatment by using another appropriate method of assessment.

  • People with dementia benefit from person-centred care. This means not only respecting the person and their carer, and taking account of their perspective and interactions, but tailoring the management to them as an individual.
  • People with dementia should not be discriminated against when considering treatment options for other conditions. They should benefit from support appropriate to their needs, and should not be discriminated against in terms of race, language, religion or sexuality.
  • Early discussions should take place to allow advance planning. This involves discussion about advance statements or decisions, lasting power of attorney and preferred place of care plans. This is one of the most important reasons for early diagnosis and referral.
  • A memory assessment service should act as the single point of referral for all patients with a suspected diagnosis of dementia. 50% of those diagnosed with mild cognitive impairment go on to develop dementia, according to NICE guidelines, so primary care professionals should consider referring at this stage.
  • Valid consent should be sought for treatment, wherever possible. This may mean making information available to them in an appropriate form. The use by patients and carers of advocacy services and voluntary organisations should be encouraged. If patients are not competent to make a decision, the requirements of the Mental Capacity Act 2005 should be followed.
  • Carers should receive an assessment of needs as required by the Carers and Disabled Children Act 2004 and the Carers (Equal Opportunities) Act 2004. Carers should be offered individual or group psycho-education and psychological therapy, peer-support groups, information in a variety of media, and training courses. Issues such as transport, night-sitting, and respite care should also be considered. See the separate Supporting the Family of People with Dementia article.
  • Health and social care managers should take a joint approach to management, and this should include joint written policies and procedures, and joint planning of services which take on board the views of local service users and carers. Care managers and co-ordinators should ensure that a combined care plan, which takes account of the changing needs of the patient and the carers, is reviewed regularly, and receives the endorsement of the patient and carers. Named health and/or social care staff should be assigned to operate the plan.
  • Following diagnosis the patient and carers should be given written information about:
    • The symptoms and signs of dementia.
    • Course and prognosis.
    • Treatments.
    • Local care and support services.
    • Support groups.
    • Sources of financial and legal advice, and advocacy.
    • Medico-legal issues, including driving.
    • Local information sources, including libraries and voluntary organisations.
  • Health and social care staff should aim to promote independence where possible, including mobility. Strategies to cope with disabilities should be promoted, such as modifications to the living environment and simplification of daily activities.
  • Young people with dementia and those with learning disabilities have special needs, and require specialist advice and focused support.
  • People with mild-to-moderate dementia should be given the opportunity to participate in a structured group cognitive stimulation programme (which includes reality orientation). This may help maintain cognitive skills and day-to-day functioning.
  • Memory enhancement strategies: reminder notes, lists, reorganisation of possessions.
  • Cognitive behavioural therapy (CBT) for those with Alzheimer's disease who are experiencing depression or anxiety, involving their carers.
  • Non-pharmacological approaches for those with anxiety, depression or challenging behaviour include:
    • Aromatherapy.
    • Therapeutic use of music and dance.
    • Animal-assisted therapy.
    • Massage.
    • Multi-sensory stimulation.
    • Exercise.
    • Reminiscence therapy.
  • Volunteers should be involved where helpful and appropriate.

Four drugs are available in the UK for treatment of dementia: the acetylcholinesterase (AChE) inhibitors (donepezil, galantamine and rivastigmine) and memantine (a N-methyl-D-aspartate (NMDA) antagonist).

  • The AChE inhibitors appear to be beneficial for people with mild to moderate Alzheimer's disease[13, 14].
  • Studies have also demonstrated that memantine is cost-effective in the management of moderate and severe Alzheimer's disease[15, 16].

In 2018, NICE updated its guidance on the use of these drugs in mild and moderate Alzheimer's disease[17]:

  • The three AChE inhibitors donepezil, galantamine and rivastigmine as monotherapies are recommended as options for managing mild to moderate Alzheimer's disease.
  • Memantine monotherapy is recommended as an option for managing Alzheimer's disease for people with:
    • Moderate Alzheimer's disease who are intolerant of or have a contra-indication to AChE inhibitors; or
    • Severe Alzheimer's disease.
  • For people with an established diagnosis of Alzheimer's disease who are already taking an AChE inhibitor:
    • Consider memantine in addition to an AChE inhibitor if they have moderate disease.
    • Offer memantine in addition to an AChE inhibitor if they have severe disease.

For people who are not taking an AChE inhibitor or memantine, treatment should only be started on the advice of a clinician who has the necessary knowledge and skills - eg, secondary care medical specialists such as psychiatrists, geriatricians and neurologists, or other healthcare professionals (such as GPs, nurse consultants and advanced nurse practitioners), if they have specialist expertise in diagnosing and treating Alzheimer's disease.

For people with an established diagnosis of Alzheimer's disease who are already taking an AChE inhibitor, primary care prescribers may start treatment with memantine without taking advice from a specialist clinician.

Do not stop AChE inhibitors in people with Alzheimer's disease because of disease severity alone.

Pharmacological treatment of other features

  • Where antidepressants are needed, avoid tricyclic antidepressants and other anti-cholinergics, as they may have an adverse effect on cognition.
  • Antipsychotics should be avoided where possible in Alzheimer's disease. Where needed for psychotic features or agitation:
    • Discuss the risks (sedation, risk of stroke, worsening cognition) and consider other cerebrovascular risk factors.
    • Ideally treat under specialist advice.
    • Monitor effects regularly.
    • Use the lowest possible dose and titrate up slowly where necessary.
    • Treatment should be time limited.
    • Consider risperidone as first choice[1].
  • Occasionally aggression, violence or agitation pose a threat to safety, and where non-pharmacological measures have failed, benzodiazepines or antipsychotics may be required urgently:
    • Oral medication should be used where possible; intramuscular (IM) route is safer than intravenous (IV) where it is not possible.
    • Lorazepam, haloperidol or olanzapine should be used where IM administration is required. IM diazepam and chlorpromazine are not recommended.
    • Effects should be closely monitored.

Physical, psychological, social and spiritual support should be offered, and dementia patients should have the same access to palliative care services as any other patient. Oral nutrition should be encouraged for as long as possible. Percutaneous endoscopic gastrostomy (PEG) feeding may be appropriate in patients with transient dysphagia but is not recommended in patients with severe dementia, as there is no evidence of increased survival or reduced complications[18].

Decisions to withhold nutritional support should be taken within a legal and ethical framework. Fever may be managed with antipyretics and mechanical cooling. Palliative antibiotics should be given after an individual assessment of the patient. Resuscitation is unlikely to succeed in patients with severe dementia. If no advanced decision has been taken by the patient, the decision to resuscitate should take into account the views of the carers and the multidisciplinary team, the Resuscitation Council UK's guidance, and the Mental Capacity Act 2005. The decisions should be recorded in the notes and care plan.

  • Alzheimer's disease is a progressive condition for which there is currently no cure and no known way to slow the progression of this disease.
  • Symptoms in some people in the early and middle stages of the disease may be relieved by medication.
  • The course of Alzheimer's disease varies from person to person, with some people having the disease for five years, and others for up to 20 years.

No specific treatment is known to reduce the risk of Alzheimer's disease. However there are a number of modifiable risk factors that can be addressed (see above)[5].

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Further reading and references

  1. Dementia; NICE CKS, October 2020 (UK access only)

  2. Alzheimer Disease, AD; Online Mendelian Inheritance in Man (OMIM)

  3. Sadigh-Eteghad S, Talebi M, Farhoudi M; Association of apolipoprotein E epsilon 4 allele with sporadic late onset Alzheimer`s disease. A meta-analysis. Neurosciences (Riyadh). 2012 Oct17(4):321-6.

  4. Ward A, Crean S, Mercaldi CJ, et al; Prevalence of apolipoprotein E4 genotype and homozygotes (APOE e4/4) among patients diagnosed with Alzheimer's disease: a systematic review and meta-analysis. Neuroepidemiology. 201238(1):1-17. doi: 10.1159/000334607. Epub 2011 Dec 17.

  5. Crous-Bou M, Minguillon C, Gramunt N, et al; Alzheimer's disease prevention: from risk factors to early intervention. Alzheimers Res Ther. 2017 Sep 129(1):71. doi: 10.1186/s13195-017-0297-z.

  6. Dementia: assessment, management and support for people living with dementia and their carers; NICE Guideline (June 2018)

  7. The ICD-10 Classification of Mental and Behavioural Disorders; World Health Organization

  8. Highlights of Changes from DSM-IV-TR to DSM-5; American Psychiatric Association, 2013

  9. McKhann GM, Knopman DS, Chertkow H, et al; The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May7(3):263-9. doi: 10.1016/j.jalz.2011.03.005. Epub 2011 Apr 21.

  10. Albert MS, DeKosky ST, Dickson D, et al; The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May7(3):270-9. doi: 10.1016/j.jalz.2011.03.008. Epub 2011 Apr 21.

  11. Dementia; NICE Quality Standard, June 2010

  12. Dementia: independence and wellbeing; NICE Quality Standard, April 2013

  13. Birks JS, Grimley Evans J; Rivastigmine for Alzheimer's disease. Cochrane Database Syst Rev. 2015 Apr 10(4):CD001191. doi: 10.1002/14651858.CD001191.pub3.

  14. Birks J; Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev. 2006 Jan 25(1):CD005593.

  15. Rive B, Grishchenko M, Guilhaume-Goulant C, et al; Cost effectiveness of memantine in Alzheimer's disease in the UK. J Med Econ. 201013(2):371-80. doi: 10.3111/13696998.2010.491347.

  16. Howard R, McShane R, Lindesay J, et al; Donepezil and memantine for moderate-to-severe Alzheimer's disease, N Engl J Med 2012 366:893-903

  17. Donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer's disease; NICE Technology Appraisal Guidance, March 2011 - updated June 2018

  18. Sampson EL, Candy B, Jones L; Enteral tube feeding for older people with advanced dementia. Cochrane Database Syst Rev. 2009 Apr 15(2):CD007209.

Hi my mother seems to loose the ability to walk at night times. She is awaiting memory tests for possible vascular dementia or Alzheimer’s. It seems to happen suddenly, one moment she is walking with...

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