Alzheimer's Disease

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 Cholinesterase Inhibitors for Dementia. No curative medication or medication to prevent the progress of the disease is available so far.

Risk factors and protective factors

• See T1

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

Treatment Atypical Antipsychotics for Aggression and Psychosis in Alzheimer's Disease, Metal Protein Attenuating Compounds for Alzheimer's Disease, High-Dose B Vitamins in Alzheimer's Disease, Statins for the Treatment of Alzheimer's Disease, Aspirin, Steroidal and Non-Steroidal Anti-Inflammatory Drugs for the Treatment of Alzheimer's Disease, Pharmacotherapies for Sleep Disturbances in Dementia, Hormone Replacement Therapy to Maintain Cognitive Function in Women with Dementia, Nimodipine for Dementia

• The acetylcholinesterase inhibiting drugs donepezil Donepezil for Alzheimer's Disease, rivastigmine Rivastigmine for Alzheimer's Disease and galantamine Galantamine for Alzheimer's Disease 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 Memantine for Dementia.
• The combination of memantine and an acetylcholinesterase inhibitor (donepezil, galantamine, rivastigmine) appears to be both beneficial and safe Memantine Combined with Donepezil in Alzheimer's Disease.
• 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 Treatment of a Patient with Memory Disease.
• Many drug trials with the aim to slow the progress of the disease are ongoing.
• Treatment of dementia: see Treatment of a Patient with Memory Disease.

References

• 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 [PubMed]
• 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. [PubMed]
• 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. [PubMed]
• 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. [PubMed]
• 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. [PubMed]