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Alzheimer's disease

Background

Overview

Definition
Alzheimer's disease is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and functional impairment.
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Pathophysiology
Alzheimer's disease is characterized by two primary pathophysiological mechanisms: the accumulation of amyloid-beta plaques and the formation of neurofibrillary tangles. In addition, neuroinflammation, characterized by alterations in the functional responses of microglia and astrocytes and dysregulation of pro- and anti-inflammatory cytokines, also plays a significant role in the pathophysiology of Alzheimer's disease.
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Epidemiology
The prevalence of Alzheimer's disease worldwide is estimated at 598.97 per 100,000 population.
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Disease course
Clinically, Alzheimer's disease presents with progressive memory decline as well as cognitive deficits with executive dysfunction, language, visual perceptual difficulties, apraxia, and agnosia. Emotional and behavioral symptoms may also emerge in the moderate-to-severe stages of the disease.
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Prognosis and risk of recurrence
Alzheimer's disease is a chronic condition with no known cure. The prognosis is typically poor as the disease progressively worsens over time. The life expectancy following a diagnosis of Alzheimer's disease can vary between 3 to 10 years, with age being a significant predictor.
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Guidelines

Key sources

The following summarized guidelines for the evaluation and management of Alzheimer's disease are prepared by our editorial team based on guidelines from the European Neurological Society (ENS/EAN/EFNS 2015), the American Academy of Family Physicians (AAFP 2011), and the European Federation of Neurological Societies (EFNS 2010). ...
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Screening and diagnosis

Screening for comorbidities: as per EFNS 2010 guidelines, assess patients with Alzheimer's disease for comorbidity, both at the time of diagnosis and throughout the course of the illness
E
and always consider it as a possible cause of behavioral and psychological symptoms of dementia.
B
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Diagnostic investigations

History and physical examination: as per EFNS 2010 guidelines, elicit a clinical history supplemented by an informant.
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  • Cognitive assessment

  • Laboratory studies

  • Imaging

  • Electroencephalography

  • Genetic testing

Diagnostic procedures

CSF analysis
As per EFNS 2010 guidelines:
Obtain routine CSF analysis in the differential diagnosis of atypical clinical presentations of Alzheimer's disease.
E
Obtain CSF 14-3-3 or total tau protein measurements for the identification of Creutzfeldt-Jakob disease in patients with rapidly progressive dementia. Alterations in CSF total tau, phospho-tau and Ab42 support diagnosis of Alzheimer's disease.
B

Medical management

Cholinesterase inhibitors: as per AAFP 2011 guidelines, offer cholinesterase inhibitors for patients with mild-to-moderate Alzheimer's disease based on their modest effectiveness, although limited by their adverse effects.
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  • Memantine

  • Antipsychotics

  • Lecanemab

  • Other medications

Nonpharmacologic interventions

Cognitive stimulation: as per EFNS 2010 guidelines, consider cognitive stimulation or rehabilitation in patients with mild-to-moderate Alzheimer's disease.
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  • Occupational therapy

  • Addressing behavioral and psychological symptoms of dementia

Specific circumstances

Patients with depression: as per EFNS 2010 guidelines, offer SSRIs rather than TCAs for the treatment of depression in patients with Alzheimer's disease.
B

Patient education

Diagnosis disclosure: as per EFNS 2010 guidelines, disclose the diagnosis of Alzheimer's disease to patient (and caregivers as appropriate), which should be individually tailored and accompanied by information and counseling, as well as useful contacts such as Alzheimer's disease patient organizations.
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  • Patient and caregiver education

  • Addressing patient needs and preferences

Preventative measures

Prevention
As per EFNS 2010 guidelines:
Insufficient evidence to support the use of any drugs purely for the primary prevention of dementia.
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Insufficient evidence to support the use of anti-inflammatory drugs, nootropics (including piracetam, nicergoline), selegiline, estrogens, pentoxyphylin, statins, EGb 761 and Cerebrolysin for the prevention of Alzheimer's disease.
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Follow-up and surveillance

Discontinuation of medical therapy: as per AAFP 2011 guidelines, consider discontinuing treatment for patients with Alzheimer's disease who continue to experience decline despite maximal therapy.
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  • Follow-up