Alzheimer disease (AD) is a chronic neurodegenerative disease and the leading cause of dementia. Several causative gene defects (e.g., amyloid precursor protein gene mutations) and risk factors (e.g., old age) have been identified, although the exact mechanism that causes Alzheimer disease is still unknown. The main histopathological features of AD are senile plaques caused by the extracellular deposition of beta-amyloid protein (Aβ protein) in the grey matter of the brain and neurofibrillary tangles due to intracellular accumulation of tau protein. The most common symptom of AD is short-term memory loss. Many cognitive functions, including attention control, reasoning, orientation, and language, are affected during the course of the disease. Individuals with AD are typically capable of maintaining a social façade as the disease progresses. The diagnosis is primarily based on clinical examination, but neuropsychological tests, cerebrospinal fluid (CSF) analysis, and imaging are sometimes used as well. To date, there is no curative therapy. Symptomatic therapy can be attempted with cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) antagonists (e.g., memantine). AD has a highly variable progression. The mean survival time following diagnosis is usually between 3 and 10 years.
- AD is the leading cause of dementia and the sixth most common cause of death in the US. 
Incidence and prevalence increase with age.
- ∼ 400:100,000 in individuals between 65 and 74 years of age
- ∼ 3200:100,000 in individuals 75–84 years of age
- ∼ 7600:100,000 in individuals ≥ 85 years of age
Prevalence: A total number of ∼ 5.8 million individuals in the US have Alzheimer disease.
- 65–74 years of age: 1 million individuals (17%)
- 75–84 years of age: 2.7 million individuals (47%)
- ≥ 85 years of age: 2.1 million individuals (36%)
- Sex: ♀ > ♂
- Early-onset (before the age of 65) familial AD represents ∼ 10% of all AD cases
Epidemiological data refers to the US, unless otherwise specified.
Genetic factors 
|Overview of genetic factors in Alzheimer disease|
|Amyloid precursor protein (APP) gene|
|Presenilin-2 || || |
Other risk factors 
- Age (strongest predisposing factor for regular AD)
- Family history of dementia (strongest predisposing factor for early-onset AD)
- Low socioeconomic and/or educational status
- Diabetes, obesity, dyslipidemia
- Hypertension, peripheral atherosclerosis, and cerebrovascular disease
- African American or Hispanic descent (compared to White individuals)
- Lack of physical activity (independent risk factor)
- Traumatic brain injuries
- Environmental factors (e.g., secondhand smoke)
- Sleep deprivation
The following pathophysiological mechanisms contribute to AD: 
- Senile plaques (neuritic plaques)
- Neurofibrillary tangles
- Reduced cholinergic function
- Common symptoms of cognitive impairment
- Less common symptoms
- Agitation, aggression, irritability
- Mood disorders (e.g., symptoms of depression)
- Urinary incontinence
- Anxiety and mutism
- Hallucinations and paranoia
Patients with mild to moderate AD are often able to maintain a social facade and preserve certain skills (e.g., dressing, hygiene routines).
- Use neuropsychological testing (e.g., , ) to diagnose dementia in patients with memory loss, cognitive and/or functional decline.
- Rule out reversible causes of dementia.
- AD can only be confirmed via neurohistopathological examination, which can only be conducted post mortem.
Synopsis of diagnostic criteria
- Insidious onset (symptoms are often first noticed by the patient's relatives)
- Objectively confirmed progressive loss of function in at least two cognitive domains; (usually including memory impairment)
- Impaired activities of daily living (e.g., difficulties at the workplace)
- No other plausible explanation (e.g., delirium)
- Cognitive testing: Repeated performance measurement is used to track disease progression.
- Functional Assessment Questionnaire (FAQ)
- Physical Self-Maintenance Scale (PSMS)
- Global testing: Global Deterioration Scale (GDS)
- Caregiver-based testing: Neuropsychiatric Inventory (NPI)
- Slower basic rhythm
- Evoked potentials: long latency
- Cerebral atrophy
- Amyloid beta (Aβ): stains with Congo red under polarization
- Tau protein: intracellular neurofibrillary tangles that stain with Gallyas silver
- Hirano bodies
The differential diagnoses listed here are not exhaustive.
There is currently no curative therapy available.
Pharmacological treatment of dementia
- Mild–moderate (determined by neuropsychological testing): acetylcholinesterase inhibitors
- Moderate–severe (may be given in addition to acetylcholinesterase inhibitors): NMDA-receptor antagonist (memantine)
- Aggression and psychosis: low dose antipsychotics
Supportive care (nonpharmacological treatment)
- Adhering to a regular sleep schedule
- Maintaining a familiar environment
- Removing ambient noise
- Cognitive rehabilitation: memory training (e.g., puzzles, interactive games) to support memory retention and strategies to compensate for cognitive and functional decline
- Physical activity: improves physical strength, which slows functional decline
Pharmacological treatment of associated symptoms
In patients who have not adequately responded to supportive care, the following classes of drugs may be considered:
- Atypical antipsychotics (e.g., risperidone): in individuals showing signs of agitation, hallucinations, insomnia
- SSRIs (e.g., citalopram): in individuals with depression
- Infections: Aspiration pneumonia is the most common contributing factor to AD-related mortality.
- Intracerebral hemorrhage (↑ risk due to cerebral amyloid angiopathy)
We list the most important complications. The selection is not exhaustive.
The mean survival time is ∼ 3 to 10 years after diagnosis.