Essentials

  • Usually begins with memory disturbances: the patient´s ability to learn fails to learn new things is reduced.
  • Clinical diagnosis is correct in about 90% of cases.
  • The progress of the disease is usually slow but steady, although periods of slower and faster deterioration may occur. Disease duration from the first symptoms to death is approximately 12 years (range from 2 to over 20 years).
  • Medication offers some help by improving functional capacity and alleviating cognitive and behavioural symptoms. However, not all patients benefit from medication and the effect may reduce over time A. No curative medication or medication to prevent the progress of the disease is available so far.

Risk factors and protective factors


Table 1. Risk factors and protective factors of Alzheimer’s disease
Risk factorsProtective factors
Younger age
Family history
Elevated blood pressure (at middle age)Treatment of elevated blood pressure
Hypercholesterolaemia (at middle age)Treatment of hypercholesterolaemia, diet containing fish and vegetables, antioxidants
Impaired glucose toleranceNormal glucose balance
Overweight (at middle age)Normal weight
SmokingNot smoking
Low level of physical activityPhysical activity
Ample use of alcohol and drugs of abuseNDSAIDs, hormone replacement therapy (at early menopause)
Earlier severe depression
Cerebrovascular diseases
Hereditary factors (especially ApoE4)
Low level of educationHigh level of education
Low level of mental activityHigh level of mental activity
Severe head trauma
Loneliness, lack of social networkSocial activity, relationship with a partner

Diagnosis

  • Core criteria
    • Significant episodic memory impairment
      • Gradual deterioration lasting for over 6 months
      • Memory impairment also observable on testing (MMSE, CERAD, a neuropsychological investigation).
      • Memory impairment can either occur as a sole cognitive symptom or be associated with other cognitive symptoms (executive function deficit, aphasia, agnosia and/or apraxia).
  • Features supporting diagnosis
    • Atrophy of the medial temporal lobe on MRI (hippocampus, entorhinal cortex, amygdala)
    • Abnormal biomarkers in the cerebrospinal fluid (decreased beta-amyloid 42 and increased tau and phospho-tau protein)
    • Typical findings on a PET scan (reduced glucose metabolism in the temporal parietal regions or detection of amyloid plaques with the aid of specific markers)
  • Signs and symptoms against Alzheimer’s disease
    • Sudden onset, early occurrence of gait disturbances, seizures or behavioural changes
    • Focal neurological findings, such as hemiparesis or early extrapyramidal signs
    • Other diseases that may account for cognitive symptoms, such as cerebrovascular disease, severe depression, other illness capable of causing dementia
  • Alzheimer’s disease can be diagnosed with certainty when
    • the clinical and neuropathological criteria are fulfilled or
    • the clinical criteria are fulfilled and the patient has the Alzheimer’s disease causing gene mutation on chromosome 1, 14 or 21.

Laboratory investigations and imaging studies

  • Alzheimer’s disease is not associated with any changes in routine laboratory investigations.
  • At present, genetic testing is not used in clinical practice due to the complexity of testing (several different genes would need to be tested for various mutations) and because the hereditary disease forms are rare compared with the overall prevalence of the disease.
  • An MRI scan is more valuable for diagnosis than a CT scan as the medial parietal lobe and hippocampal atrophy typical of Alzheimer’s disease can be better verified by an MRI scan. If the symptoms are typical, CT scanning can be used to exclude other conditions.

Progression of Alzheimer’s disease

Mild degree

  • The patient usually tries to hide or is dismissive of his/her symptoms.
  • Memory impairment (impaired ability to learn new information or to recall previously learned information)
  • Impaired visuospatial perception leading to the patient easily losing his/her way, especially in strange surroundings
  • Sense of time deteriorates.
  • Difficulty finding the right words
  • The understanding of complicated and abstract ideas becomes difficult.
  • Executive function deteriorates and complex activities of daily living, for example, pose problems.
  • The patient may be inactive and withdrawn.
  • Sometimes the patient is depressed, paranoid or even aggressive. A triggering factor can usually be identified for aggressive behaviour, such as treatment that the patient considers humiliating or procedures he/she is unable to understand.
  • Physical examination is normal.

Moderate degree

  • The patient’s insight into the illness is often lost.
  • The patient may lose his/her way even in familiar surroundings.
  • The patient may experience different hallucinations, which are, however, much more common in dementia with Lewy bodies.
  • Weight loss is inevitable, unless particular attention is paid to nutritional needs.
  • Difficulties in activities of daily living (e.g. dressing, washing).

Severe degree

  • The ability to comprehend speech and to speak is significantly impaired or totally lost.
  • The limbs stiffen with the increasing muscle tonus, and the patient adopts a stooped posture and a shuffling gate. The ability to walk will deteriorate and be totally lost, unless the patient receives appropriate physiotherapy.
  • Urinary and faecal incontinence develop.
  • Epileptic seizures may sometimes occur.
  • The patient is no longer able to cope with activities of daily living (dressing, washing, toileting and finally eating).

Treatment

  • The acetylcholinesterase inhibiting drugs donepezil A, rivastigmine A and galantamine A offer some benefit in Alzheimer's disease by improving functional capacity and alleviating cognitive and behavioural symptoms.
  • Evidence exists on the benefit of memantine in the treatment of moderate to severe Alzheimer’s disease A.
  • The combination of memantine and an acetylcholinesterase inhibitor (donepezil, galantamine, rivastigmine) appears to be both beneficial and safe B.
  • Elderly patients may develop nausea, abdominal pain and diarrhoea, particularly when high doses of donepezil, rivastigmine and galantamine are used. A transdermal rivastigmine patch is associated with a significantly lower incidence of these adverse effects.
  • The aim of treatment is to improve functional capacity and delay the need for institutional care.
  • Treatment is discontinued when it no longer is beneficial. If it is thought that the patient is no longer responding to medication when admitted to institutional care, it is possible to withdraw medication for 1–2 weeks. If further cognitive decline is observed, the medication is restarted.
  • The reimbursement status of these drugs varies from country to country.
  • In the early phase of the disease, a clinical nutritional product Souvenaid® (125 ml once daily) may be used alongside the drug therapy.
  • Suitable psychiatric medication may in some cases improve the patient’s condition, but the occurrence of adverse effects must be avoided. Risperidone at the dose 0.25–0.5 mg twice daily has been shown in clinical studies to be moderately effective for the management of behavioural symptoms. Continuous treatment periods lasting for longer than 6 weeks are not recommended.
  • The functional capacity of a patient with Alzheimer's disease can often be improved for some time by providing surroundings enriched with suitable stimuli. Comprehensive care also includes support to the family members and other informal caregivers 1.
  • Many drug trials with the aim to slow the progress of the disease are ongoing.
  • Treatment of dementia: see 2.

Evidence Summaries

References

1. Dubois B, Feldman HH, Jacova C et al. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurol 2007 Aug;6(8):734-46  [PMID:17616482]

2. Grossberg G, Sadowsky C, Fröstl H, Frölich L, Nagel J, Tekin S, Zechner S, Ros J, Orgogozo JM. Safety and tolerability of the rivastigmine patch: results of a 28-week open-label extension. Alzheimer Dis Assoc Disord 2009 Apr-Jun;23(2):158-64.  [PMID:19484917]

3. Soininen H, Solomon A, Visser PJ et al. 24-month intervention with a specific multinutrient in people with prodromal Alzheimer's disease (LipiDiDiet): a randomised, double-blind, controlled trial. Lancet Neurol 2017;16(12):965-975.  [PMID:29097166]

4. Shah RC, Kamphuis PJ, Leurgans S et al. The S-Connect study: results from a randomized, controlled trial of Souvenaid in mild-to-moderate Alzheimer's disease. Alzheimers Res Ther 2013;5(6):59.  [PMID:24280255]

5. Scheltens P, Twisk JW, Blesa R et al. Efficacy of Souvenaid in mild Alzheimer's disease: results from a randomized, controlled trial. J Alzheimers Dis 2012;31(1):225-36.  [PMID:22766770]


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