Alzheimer's disease
" I have lost my self " Auguste D, 1901.
General Overview :
Alzheimer's disease [69, 196, 197] is a neurodegenerative pathology [138, 198] that affects various regions of the brain. It is the primary [140, 199] cause of dementia [197] (an acquired, progressive, profound, and irreversible decline in cognitive functions) in the elderly.
This disease is named after Dr. Alois Alzheimer who, in 1907 [196], first described the anatomical alterations observed in the brain of a 51-year-old patient, Auguste D. [201].
In 1901 [200], Dr. Alzheimer asked the patient to state her name; Auguste tried to remember it but could not, then she looked up at the doctor and said, "I have lost myself" [202].
Pathophysiology :
The neurodegenerative process responsible for the disease involves the formation of amyloid plaques [113] (senile plaques) between neurons and, inside the neurons, aggregates of tau proteins that form neurofibrillary tangles [196].
These two phenomena cause massive neuronal destruction, which manifests macroscopically as cortical atrophy [185, 196]. In patients with Alzheimer's disease, the brain can lose 8 to 10% of its weight every ten years, compared to 2% in a healthy subject [203]. Cortical atrophy is accompanied by a dilation of the cerebral ventricles and cortical sulci.
Neuronal loss particularly affects cholinergic systems [80] (neocortex, entorhinal cortex, amygdala, hippocampus, nucleus basalis of Meynert [50, 119, 172]), noradrenergic systems (locus coeruleus), and serotonergic systems (raphe nuclei) [63].
Risk factors :
The exact causes of Alzheimer's disease remain unknown [39], but it is hypothesized that environmental factors (aluminum and heavy metals, including mercury [204]) and genetic factors [196, 197] contribute to it. Mutations in at least four genes predisposing to Alzheimer's disease have been identified.
Risk factors for developing Alzheimer's disease include:
- Age is the most significant risk factor [196]. As we age, the body's natural repair mechanisms become less effective.
- Cardiovascular disease : All risk factors for cardiovascular disease [204] (such as hypertension and hypercholesterolemia) are also risk factors for Alzheimer's disease.
- Family and genetic history [196, 197].
- The ApoE4 gene [197].
- Female sex [196].
- Diabetes [205].
- Head trauma [196, 197, 204] ...
Clinical Presentation :
The first symptom of Alzheimer's disease is the loss of memory of recent events (amnesia) [201]; this initially manifests as minor lapses that progressively worsen as the disease advances, while long-term memories are relatively preserved.
Subsequently, cognitive deficits extend to the fields of language (aphasia) [198], the organization of movements (apraxia) [205], visual recognition (visual agnosia) [197], and executive functions (such as decision-making and planning) [206]. These latter symptoms specifically reflect the pathological degenerative process affecting the frontal lobes of the brain.
These psychological changes affect essential human qualities, and for this reason, Alzheimer's is sometimes described as a disease in which victims suffer the loss of the qualities that form the essence of human existence.
Treatment :
There is currently no treatment that can cure Alzheimer's disease [206] or even stop its progression. However, some medications slow its advancement by alleviating the loss of memory, language, and reasoning.
Specific treatments :
These are medications prescribed specifically for Alzheimer's disease [207]:
- Acetylcholinesterase inhibitors: They inhibit the breakdown of acetylcholine, aiming to correct the acetylcholine deficit observed in the brains of those affected by this disease.
- NMDA antagonists: N-methyl-D-aspartate (NMDA) neuronal receptors play an important role in memorization processes.
Non-specific treatments :
These modify the patient's behavior without addressing the disease itself [206].
- Psychotropic drugs reduce anxiety, aggression, or states of agitation. Anticholinergics should be avoided as they worsen the disease.
- Medications targeting the risk factors of the disease: certain statins, antioxidants (such as vitamin E or melatonin), and anti-inflammatories.
In all cases, addressing the disruptions caused by cognitive impairment in the personal and relational lives of patients is essential, as is providing support to their families. Cognitive rehabilitation techniques and certain psychotherapies are often helpful.