In a small percentage, difficulties with language, executive functions, perception (agnosia), or execution of movements (apraxia) are more prominent than memory problems. Alzheimers disease does not affect all memory capacities equally. Older memories of the persons life (episodic memory), facts learned (semantic memory), and implicit memory (the memory of the body on how to do things, such as using a fork to eat or how to drink from a glass) are affected to a lesser degree than new facts or memories.Language problems are mainly characterised by a shrinking vocabulary and decreased word fluency, leading to a general impoverishment of oral and written language. In this stage, the person with Alzheimers is usually capable of communicating basic ideas adequately. While performing fine motor tasks such as writing, drawing, or dressing, certain movement coordination and planning difficulties (apraxia) may be present, but they are commonly unnoticed. As the disease progresses, people with Alzheimers disease can often continue to perform many tasks independently, but may need assistance or supervision with the most cognitively demanding activities. Middle stage
Progressive deterioration eventually hinders independence, with subjects being unable to perform most common activities of daily living. Speech difficulties become evident due to an inability to recall vocabulary, which leads to frequent incorrect word substitutions (paraphasias). Reading and writing skills are also progressively lost. Complex motor sequences become less coordinated as time passes and Alzheimers disease progresses, so the risk of falling increases. During this phase, memory problems worsen, and the person may fail to recognise close relatives.
In Alzheimers disease, tau undergoes chemical changes, becoming hyperphosphorylated; it then begins to pair with other threads, creating neurofibrillary tangles and disintegrating the neurons transport system. Pathogenic tau can also cause neuronal death through transposable element dysregulation. Disease mechanism
Exactly how disturbances of production and aggregation of the beta-amyloid peptide give rise to the pathology of Alzheimers disease is not known. The amyloid hypothesis traditionally points to the accumulation of beta-amyloid peptides as the central event triggering neuron degeneration. Accumulation of aggregated amyloid fibrils, which are believed to be the toxic form of the protein responsible for disrupting the cells calcium ion homeostasis, induces programmed cell death (apoptosis). It is also known that Aβ selectively builds up in the mitochondria in the cells of Alzheimers-affected brains, and it also inhibits certain enzyme functions and the utilisation of glucose by neurons.Various inflammatory processes and cytokines may also have a role in the pathology of Alzheimers disease. Inflammation is a general marker of tissue damage in any disease, and may be either secondary to tissue damage in Alzheimers disease or a marker of an immunological response. There is increasing evidence of a strong interaction between the neurons and the immunological mechanisms in the brain. Obesity and systemic inflammation may interfere with immunological processes which promote disease progression.Alterations in the distribution of different neurotrophic factors and in the expression of their receptors such as the brain-derived neurotrophic factor (BDNF) have been described in Alzheimers disease.