Alzheimer's Disease

Essentials

• Alzheimer's disease (AD) progresses from a clinically asymptomatic phase to an early disease stage and then stages that involve dementia.
• Diagnostic examinations concerning AD should be started when mild cognitive changes appear (early stage).
• In the most common type of Alzheimer's disease, the symptoms focus on memory problems (about 85% of cases).Symptoms usually begin as memory disturbances: the patient´s ability to learn new things is reduced.
• Atypical disease forms include posterior cortical atrophy (PCA), logopenic progressive aphasia (LPA), and, beginning with behavioural symptoms, a disease form that resembles frontal lobe dementia. The early symptoms, before clear symptoms of memory loss, may involve impairment of visual perception, linguistic functions or executive functioning, or behavioural symptoms.
• Clinical diagnosis is correct in about 90% of cases.
• The progress of AD is usually slow but steady, although periods of slower and faster deterioration may occur. Disease duration from the first symptoms to death is 12 years on average (range from 2 to over 20 years).
• Individually planned services and support activities are the starting point of the treatment.
• Response to pharmacotherapy can be seen as improved/preserved functional capacity, alleviation of neuropsychiatric symptoms and preservation of cognitive functioning (primarily through improvement of mental alertness, no effect on memory) Cholinesterase Inhibitors for Alzheimer's Disease. 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 symptoms include
  • Significant impairment of episodic memory, visuospatial perception or linguistic functions such as speech production or ability to comprehend speech.
  • Mild depressive symptoms, suspiciousness, apathy and agitation are common already in early AD.
• Biological signs supporting diagnosis
  • On MRI or CT scan, atrophy of the medial temporal lobe (hippocampus, entorhinal cortex, amygdala) or atrophy of the parietal lobel focusing on the region of the cingulate gyrus (posterior cortical atrophy)
  • Abnormal biomarkers in the cerebrospinal fluid (decreased beta-amyloid 42 and increased tau and phospho-tau protein concentrations)
  • Typical findings on a PET scan (reduced glucose metabolism in the temporoparietal cortical or posterior cingulate gyrus regions or detection of amyloid plaques with the aid of specific markers)
• Symptoms and signs against Alzheimer's disease
  • Sudden onset, early occurrence of gait disturbances, seizures
  • Focal neurological findings, such as hemiparesis or early extrapyramidal symptoms
  • 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.
• Since Alzheimer's disease caused by a single gene change is very rare, the criteria required for a certain diagnosis are fulfilled only rarely during an individual's lifetime, and therefore gene testing is usually not performed in persons with AD. Usually, a criteria-based diagnosis of probable Alzheimer's disease is set.

Laboratory investigations

• Alzheimer's disease is not associated with any changes in routine laboratory investigations.
• At present, genetic testing is not generally 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.

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, Omega-3 Fatty Acid for the Treatment and Prevention of Alzheimer's Disease, Cholinesterase Inhibitors for Alzheimer's Disease

• Making an appropriate, early diagnosis either by a neurologist, geriatrician or a physician familiar with memory diseases as well as early treatment and rehabilitative measures are cost-effective.
• Comprehensive therapy also involves support for relative(s) caring for the patient Treatment of a Patient with Memory Disease.
• With individually planned services and supportive measures as well as targeted, appropriately timed pharmacotherapy, it is possible to postpone the need for long-term care and to support the continuation of a lifestyle as familiar as possible to the patient.
• Provision of support and non-pharmacological therapies
  • Assessment of risks in the environment: safety at home and in nearby areas, driving ability, hobbies, mental stimulation, connections to the relatives and support services
  • Clarify what is the patient's ability to decide on matters that concern him/herself and, for example, the ability to understand his/her economic situation.
  • At the early phase, it is useful to prepare for the future, such as by making a living will and an authorisation to supervise one's interests. Find out about local policies.
  • Review of current medication and, if possible, discontinuation of drugs that entail harmful effects (anticholinergic drugs, benzodiazepines, other sedative drugs). If the patient is losing weight, the cause may also be in too strong other medication, such as drugs for diabetes or blood pressure.
  • Appropriate, safe physical exercise and muscle excercises to maintain balance
  • Potential therapy forms include music therapy Music-Based Therapeutic Interventions for People with Dementia, arts, dance, mainentance of manual skills.
• Pharmacotherapy for the memory disease
  • The aim of the therapy is to maintain/improve functional capacity, to prevent the development of behavioural symptoms and alleviate them, and to prolong the time of coping in outpatient care.
  • The benefit of pharmacotherapy may only be assessed after about half a year from its start. Not all patients benefit from these drugs and their effect may decrease over time.
  • Response to pharmacotherapy can be seen as improved/preserved functional capacity, alleviation of neuropsychiatric symptoms and preservation of cognitive functioning (primarily through improvement of mental alertness, no effect on memory)
  • When starting pharmacotherapy, it is necessary to monitor the patient, and the benefits and harms must be assessed individually.
  • Pharmacotherapy is discontinued when it is no longer beneficial. If, when the patient enters institutional care, it is suspected that the effect of a drug has ended, discontinuing the medication for a period of 1-2 weeks may be tried. If functional capacity reduces or neuropsychiatric symptoms increase, the medication is started again.
  • Of acetylcholinesterase inhibiting drugs (AChEIs) donepezil Donepezil for Alzheimer's Disease, rivastigmine Rivastigmine for Alzheimer's Disease and galantamine Galantamine for Alzheimer's Disease are available.
    • An ECG must be performed before starting AChEI therapy.
    • Contraindications to AChEIs include, among others, sick sinus syndrome without pacemaker, recent myocardial infarction and peptic ulceration.
    • No significant differences in the relative efficacy of the drugs has been detected.
    • Possible gastroinstestinal adverse effects include nausea, abdominal pain and diarrhoea. Oral drugs must always be taken after a meal to prevent these adverse effects.
    • A transdermal rivastigmine patch is associated with less gastrointestinal adverse effects compared with drugs in tablet form.
    • In order to minimize adverse effects, the medication should be started using a small dose and increasing the dose gradually until maintenance dose has been reached.
  • Evidence exists on the benefit of memantine in the treatment of moderate to severe Alzheimer's disease Memantine for Alzheimer's Disease. Memantine can be combined with an AChEI.Combination Therapy with Cholinesterase Inhibitors and Memantine for Alzheimer's Disease
  • Find out about locally relevant reimbursement policies.
  • Several studies concerning pharmacotherapy for AD are underway, with the aim to slow down disease progress.
• Nutritional products
  • It has been suggested that a clinical nutritional product would slow down the development of symptoms and cerebral changes and to preserve functional capacity when the treatment is started at the early stage. There is no evidence on benefit in the moderate stage.
  • In a meta-analysis involving 3 randomized trials and over 1 000 patients, no clear evidence on slowing down the disease progress was found Dietary Supplement (Souvenaid® ) for Alzheimer's Disease.
  • In a newer (2021) trial 3, the clinical nutritional product slowed down the progress of symptoms and cerebral changes in the early stage disease, and the beneficial effect lasted for 3 years.
• Other medication
  • The patients are susceptible to adverse effects of sedative drugs. To the extent possible, these drugs should be avoided or they should be used for as short periods and in as low doses as possible for the treament of difficult neuropsychiatric symptoms.
  • Low doses of intermediate-acting benzodiazepines may be used for a short time in the treatment of neuropsychiatric symptoms of a patient with AD, as necessary and after careful consideration if AChEIs or memantine do not provide adequate alleviation of such symptoms. Benzodiazepines do, however, impair cognitive information processing functions and increase the risk of confusion and falling.
  • Antidepressant medication may be indicated if AD is associated with moderate or severe depressive state. Antidepressants for Depression in Dementia
  • Antipsychotic medication may sometimes be needed, if non-pharmacological treatment methods or AChEIs do not have an effect on behavioural symptoms, but one should watch out for adverse effects Atypical Antipsychotics for Agitation and Psychosis in People with Alzheimer's Disease and Vascular Dementia.
    • Risperidone at the dose 0.25-0.5 mg twice daily has been shown to be moderately effective for the management of behavioural symptoms in a severe disease, and this is an official indication of the drug. Often risperidone causes, however, extrapyramidal symptoms already at a low dose. Continuous treatment lasting longer than 6 weeks is not recommended.
    • Quetiapine and olanzapine are usable in low doses, but neuropsychiatric symptoms of AD are not their official indication.
• For treatment of a patient with memory disease, see Treatment of a Patient with Memory Disease.