Alzheimer's disease

Alzheimer's disease
Name	Alzheimer's disease
Synonyms	Alzheimer disease, AD
Caption	Alois Alzheimer, who first described the condition.
Field	Neurology, Psychiatry
Symptoms	Memory loss, disorientation, mood swings
Complications	Pneumonia, Malnutrition
Onset	Typically over 65 years old
Duration	Long-term
Types	Early-onset, Late-onset
Causes	Poorly understood, involves plaques and tangles
Risks	Aging, APOE ε4 allele, Down syndrome
Diagnosis	Based on symptoms and cognitive testing
Differential	Normal aging, Vascular dementia, Lewy body dementia
Prevention	Possibly Mediterranean diet, exercise
Treatment	Cholinesterase inhibitors, Memantine
Medication	Donepezil, Rivastigmine, Galantamine
Prognosis	Life expectancy 3–9 years after diagnosis
Frequency	~50 million worldwide (2020)
Deaths	Major cause of disability and death in the elderly

Alzheimer's disease is a progressive neurodegenerative disorder and the most common cause of dementia. It is characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain, leading to the death of nerve cells and loss of brain tissue. The disease typically begins with mild memory loss and can advance to severe impairment in cognition, behavior, and the ability to carry out daily activities. While age is the greatest known risk factor, the exact cause remains unclear and there is no known cure, with current treatments focusing on managing symptoms.

Signs and symptoms

The earliest symptom is often difficulty remembering recent events, known as short-term memory loss. As it progresses, symptoms expand to include impairments in language, visuospatial abilities, and executive function, often leading to disorientation in familiar places like one's own neighborhood. Behavioral and psychological symptoms, such as apathy, depression, agitation, and psychosis, are common and can be particularly distressing. In advanced stages, individuals become fully dependent on caregivers, with basic functions like swallowing impaired, increasing risk for complications like aspiration pneumonia.

Causes and pathophysiology

The disease process is strongly associated with the abnormal accumulation of proteins in and around brain cells. A central hypothesis, the amyloid hypothesis, posits that the deposition of amyloid-beta peptides into plaques is a key initiating event. Inside neurons, the tau protein becomes hyperphosphorylated, forming insoluble neurofibrillary tangles that disrupt cellular transport. Major genetic risk factors include alleles of the apolipoprotein E (APOE) gene, particularly the ε4 allele. Rare autosomal dominant forms are linked to mutations in genes like APP, PSEN1, and PSEN2. Other implicated risk factors include a history of traumatic brain injury, cardiovascular disease, and hypertension.

Diagnosis

Diagnosis is primarily clinical, based on medical history, observation of behavior, and cognitive tests from the patient and close associates. Standardized assessment tools like the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment (MoCA) are commonly used. To rule out other causes, physicians may employ neuroimaging techniques such as MRI or PET scans, which can show brain atrophy or detect amyloid plaques. Cerebrospinal fluid analysis for amyloid and tau proteins, available at specialized centers like the Mayo Clinic or Massachusetts General Hospital, can support the diagnosis. A definitive diagnosis historically requires post-mortem examination of brain tissue.

Management

No treatment halts or reverses the underlying progression. Pharmacological management focuses on symptom modulation using cholinesterase inhibitors such as donepezil, rivastigmine, and galantamine, or the NMDA receptor antagonist memantine. Non-pharmacological approaches are critical and include cognitive stimulation, structured routines, and modifications to the living environment. Caregiver support and education are essential, with organizations like the Alzheimer's Association and Alzheimer's Society providing resources. Managing co-existing conditions, such as those treated by the NIH, and addressing safety concerns like wandering are central to care plans.

Epidemiology

It is a global health concern and a leading cause of disability among older adults. According to Alzheimer's Disease International, an estimated 50 million people worldwide were living with dementia in 2020, a figure projected to nearly triple by 2050. Advancing age is the strongest risk factor, with prevalence roughly doubling every five years after age 65. The incidence and prevalence vary by region, with higher rates reported in North America and Western Europe compared to Africa and South Asia, though this may reflect differences in diagnosis and life expectancy. The economic burden is immense, with costs in the United States alone estimated in the hundreds of billions of dollars annually.

History and society

The condition was first described by the German psychiatrist and neuropathologist Alois Alzheimer in 1906, following his examination of patient Auguste Deter at the Frankfurt Asylum. The term "Alzheimer's disease" was coined by his colleague Emil Kraepelin in the eighth edition of his textbook *Psychiatrie*. Significant research milestones include the identification of the amyloid protein by George Glenner in 1984 and the establishment of major research frameworks by the National Institute on Aging and the Alzheimer's Association. Cultural depictions, such as in the film *Iris*, and advocacy by figures like former First Lady Nancy Reagan have raised public awareness. The global response includes initiatives like the WHO's Global Dementia Observatory and ongoing clinical trials at institutions like the University of California, San Diego.

Category:Alzheimer's disease Category:Neurodegenerative disorders Category:Geriatrics