Alzheimer's Disease

Epidemiological data

Alzheimer's disease (Morbus Alzheimer) is a progressive neurodegenerative disorder that affects higher cognitive functions and often behavior. It was first described by Alois Alzheimer in 1906 and is the most common cause of dementia in old age. As life expectancy increases worldwide, the disease is becoming a major public health problem. It is estimated that around 50 million people worldwide (of all sexes and ages) now suffer from Alzheimer's disease. The most recent figures indicate that the total number of people with Alzheimer's disease in Europe will double by 2050.

Pathophysiology

The pathophysiology of Alzheimer's disease involves the accumulation of beta-amyloid plaques and neurofibrillary tangles of hyperphosphorylated tau protein in the brain. The abnormal accumulation of these factors causes dysfunction of neuronal synapses, neuronal loss and brain atrophy, particularly in the hippocampus and cortex, areas critical for memory and other higher cognitive functions.

Risk factors

Alzheimer's disease is a multifactorial disease, and its onset involves the interaction of genetic and environmental factors. A distinction is made between hereditary (familial) and sporadic forms of the disease. The sporadic form of the disease accounts for 98-99% of cases and occurs in people over the age of 65. The familial form of the disease, with age of onset < 65 years, accounts for the remaining 1-2% of cases.

Although the exact cause of the disease remains unknown, several risk factors have been identified. The most important is age, with the incidence of the disease in the general population increasing significantly in people over the age of 65. Inherited factors include mutations in the APP, PSEN1 and PSEN2 genes in the early-onset (familial) form of the disease, and the presence of the ε4 allele of apolipoprotein E (ApoE4) in the late-onset or sporadic form of the disease. Other aggravating factors include a history of head injury, the coexistence of poorly controlled cardiovascular factors (arterial hypertension, hyperlipidemia, obesity, diabetes mellitus), mental and intellectual inactivity, abuse (smoking, alcohol), the use of psychotropic substances and drugs and, in general, a low level of education and standard of living.

Clinical picture

The disease usually begins with mild memory impairment, mainly with difficulty recalling recent events (immediate or recent memory). As the disease progresses, there is an impairment of oral language with difficulty in finding the appropriate words (naming objects) and a significant limitation of the vocabulary used, spatio-temporal disorientation, limitation of critical faculties, difficulty in solving problems, mood disorders (anxiety, sadness), psychomotor slowing, episodes of confusion, behavioral changes (apathy, irritability, obsessions, paranoid ideation), functional impairment and gradual loss of autonomy. In advanced stages, the patient may lose the ability to communicate, recognize faces and perform basic self-care.

Diagnosis

Diagnosis is mainly clinical and is based on an individual and family history, a detailed clinical examination, cognitive assessment with appropriate tests (MMSE, MoCA, ACE-R, etc.) and imaging with MRI or CT of the brain. Functional imaging (e.g. amyloid PET/CT), genetic testing and lumbar puncture to look for biomarkers (amyloid Ab 1-42, total/phosphorylated tau protein) in the cerebrospinal fluid are increasingly used, especially in a research context or in specialized centers.

Treatment options

Unfortunately, there is currently no cure for Alzheimer's disease. Treatment focuses on managing symptoms and slowing the progression of the disease. Acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine) and the NMDA receptor antagonist memantine are used with limited benefit. Newer drugs such as anti-amyloid monoclonal antibodies (lecanemab, donanemab) have been approved by the US Food and Drug Administration (FDA) for patients with mild disease, with satisfactory results in slowing cognitive decline.

Non-pharmacological interventions such as cognitive enhancement, physical exercise, social contact, healthy diet (such as the Mediterranean diet), regular hydration, behavioral therapy and physiotherapy, occupational therapy and speech therapy approaches contribute significantly to the functionality and quality of life of the patient. At the same time, caregiver support and counselling and planning for the patient's future care are needed.