- Clinical science
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. 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 3–10 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.
- Sex: ♀ > ♂
- In the US, AD is more common in African Americans and Hispanics than in whites.
Epidemiological data refers to the US, unless otherwise specified.
|Amyloid precursor protein (APP) gene|
|Apo ε||Apolipoprotein E (ApoE)|
Other risk factors
- Family history of dementia
- Low socioeconomic and/or educational status
- Diabetes, obesity, dyslipidemia
- Hypertension, peripheral atherosclerosis, and cerebrovascular disease
- 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:
- Extracellular senile plaques (neuritic plaques) in the grey matter of the brain
- Intracellular neurofibrillary tangles
- Overall reduction of cholinergic function
- Common symptoms of cognitive impairment
- Short-term memory impairment (insidious onset, slow progress with episodic memory affected first)
- Language impairment
- Temporal and spatial disorientation (patients are usually not oriented to person, place, time, or events)
- Impairment of executive functions and judgment
- Less common symptoms
- Aggression, irritability, and agitation
- Mood disorders (e.g., symptoms of depression)
- Anxiety and mutism
- Hallucinations and paranoia
- Urinary incontinence
Patients with mild to moderate AD are often able to maintain a social facade and preserve certain skills (e.g., dressing, hygiene routines).
- To diagnose dementia in patients with memory loss, cognitive and/or functional decline: neuropsychological testing (e.g., , )
- Rule out reversible causes of dementia.
- AD can only be definitively diagnosed with neurohistopathological examination, which is only 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)
- Cerebrospinal fluid
EEG: slower basic rhythm
- Evoked potentials: long latency
- Neuropsychological testing (e.g., MMSE and MoCA): Repeated performance measurement is used to track disease progression.
- Cerebral atrophy
- Amyloid beta (Aβ): stains with Congo red under polarization
- Intracellular neurofibrillary tangles
- Stain with Gallyas silver.
The differential diagnoses listed here are not exhaustive.
There is currently no curative therapy; only symptomatic therapies are available.
Pharmacological treatment of dementia
- Mild-moderate (determined by neuropsychological testing): donepezil, galantamine, rivastigmine (acetylcholinesterase inhibitors)
- Moderate-severe (may be given in addition to acetylcholinesterase inhibitors): memantine (NMDA-receptor antagonist)
- Aggression and psychosis: low dose antipsychotics
Supportive care (nonpharmacological treatment)
- Lifestyle modifications; : e.g., 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 patients with agitation, hallucinations, insomnia
- SSRIs (e.g., citalopram): in patients with depression
The reported survival rate is approximately 3 to 10 years after diagnosis.