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Table of Contents
Origin and Background
In 1906, a German psychiatrist and neuropathologist by the name of Alois Alzheimer was drawn to the case of a woman showing unusual symptoms. Post mortem analysis of the brain tissue of the woman, started the journey of Dr. Alzheimer’s description of the neurodegenerative disease (Hippius, 2013). Alzheimer disease is an incurable disorder of cognitive and behavioural impairment with a long and progressive timeline. 75% of patients with dementia are thought to have genetically based Alzheimer’s, however the incidence can also be sporadic (Chapman et al, 2006). In Alzheimer’s, misfolded amino acid aggregates known as plaques develop in brain areas and impact and impede neuronal communication causing brain cell atrophy. This neurodegeneration begins in the hippocampus, then spreads to the rest of the brain over time and increasing severity of the disease. The affected region of the brain is the reduction of the memory encoding hippocampus, along with associated regions of the cerebral cortex involved in thinking, decision making, and planning (Purohit et al, 1998)
Symptoms
At first, language, strength, reflexes, sensory capacities and motor skills are spared. Memory loss increases as the disease progresses, often leading to confusion. Cognitive abilities such as problem solving, language, calculation and visuospatial skills are compromised with progression of the disease (Kandel et al, 2013). Due to the loss of cognitive abilities, experiencing psychotic symptoms are common such as hallucinations and delusions. Mental functions and the ability to carry out usual daily activities become impaired (Kandel et al, 2013). The late stages of Alzheimer's are related to becoming mute, loss of autonomic functions and eventually becoming bedridden, relying completely on a caregiver (Kandel et al, 2013). Because shrinkage of the amygdala is also a hallmark of Alzheimer’s, it is associated with mood changes.
Disease Progression
Mild: Patients with Alzheimer's may show physiological changes in the brain 10- 20 years prior to showing any symptoms. Shrinkage of the amygdala brings about symptoms of emotional outbursts and mood changes (Purohit et al, 1998)
Moderate: Memory loss at this stage advances to confusion of location in familiar places and poor judgement, mood changes, increased anxiety and language impairment (Hippius, 2013).
Severe: Plaques and tangles become widespread, memory loss advances to severe dementia and atrophy of other brain regions leads to progressive loss of autonomic functions (Hippius, 2013).
Neuropathology
Figure 3:This figure shows a comparison of a normal brain and one with Alzheimer's disease. The atrophy and degeneration of brain tissue in the brain on the right is visible. (Alz, 2011).
Disease Mechanism
Amyloid Hypothesis
Figure 4:This figure shows a simplification of the cascade of events that occur in Alzheimer's disease as predicted by the Amyloid Hypothesis. (Karran, 2011).
Cholinergic Hypothesis
Tau Hypothesis
Intervention Strategies
Treatment
Figure 5: This figure shows two promising approaches of utilizing anti-Aβ plaque antibodies to limit the progression of Alzheimer's Disease (Schenk, 2002).