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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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Risk factors
Risk factors for Alzheimer's disease include advancing age, a family history of the disease, and a genetic predisposition, particularly the presence of the apolipoprotein E ε4 allele.
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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 American Academy of Family Physicians (AAFP 2024,2017,2011), the European Neurological Society (ENS/EAN/EFNS 2015), and the European Federation of Neurological Societies (EFNS 2010).
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Screening and diagnosis
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.
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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.
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Medical management
Cholinesterase inhibitors: as per AAFP 2017 guidelines, consider offering cholinesterase inhibitors, including donepezil (5-10 mg/day), galantamine (at least 16 mg/day), or rivastigmine (6-12 mg/day PO or 9.5 mg/day transdermally) for the treatment of cognitive and functional decline in patients with mild-to-moderate Alzheimer's disease.
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Memantine
Antipsychotics
Lecanemab
Other medications
Nonpharmacologic interventions
Physical activity: as per AAFP 2017 guidelines, offer a structured physical exercise program inp atients with Alzheimer's disease of any severity.
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Cognitive stimulation
Occupational therapy
Vitamin E
Specific circumstances
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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