Major neurocognitive diseases
Alzheimer's disease is accounted for 50-70 percent of major neurocognitive diseases. Symptoms typically appear around the age of 65, in the form of episodic (recalling or remembering time and places) memory impairment and orientation problems. Toxic accumulation of tau and amyloid proteins in the deep structure of temporal lobe called hippocampus is responsible for the impairment. Accumulation of the pathological proteins is mainly in the direction of the frontal lobe, alas later on frontal lobe dysfunction also ensues, and the memory disorder extends to other cognitive elements (learned movement patterns, actions, recalling facts, etc.), as a result a significant change in personality and mood emerges.
The second most common type of dementia (about 30 percent) is diffuse Lewy body disease (DLTB). In such cases, accumulation of the protein α-synuclein is detected in the midbrain, hypothalamus and brain areas called substantia innominata. Involvement of these areas results in impairment such as difficulty in initiating movement and stiffness of the muscles (parkinsonism), visual hallucinations and cognitive decline of varying degrees.The explanation for the movement disorder is that the connection of midbrain and the basal ganglia system is crucial in initiating movement. In many cases, the disease is accompanied by manifestation of severe autonomic dysregulation, such as blood pressure fluctuations and sweating disorders. The underlying reason is the early involvement of the main center of autonomic regulation, the hypothalamus. Occasionally, for a while the disease manifests itself only in the form of a movement disorder, and years later cognitive symptoms symptoms appear in milder forms than previously discussed. The latter group is known as dementia associated with Parkinson's disease, which is less common than DLTB. Rarer synuclein diseases presenting with movement disorders are corticobasal degeneration and progressive supranuclear palsy.
Frontotemporal dementia (FTD), which accounts for 10-15 percent of cases, in addition to abnormal tau, also presents with other proteins, such as TDP-43, FUS or progranulin, alas it is much more of a diagnostic challenge to differentiate and more subcategories exist.The characteristic pathological proteins show a different spreading pattern from Alzheimer's disease, they first appear in the frontal lobe. As a result primary symptoms are pronounced behavior and personality changes (behavioral variant) or disorder of speech formation due to involvement of the motor speech field (primary progressive aphasia). Later, due to damage to the temporal lobe, memory and speech comprehension disorders also develop.
It can be concluded, that majority of the neurocognitive diseases mentioned is caused by taupathy originated cell death. In addition, it should be emphasized that varying disease forms can significantly overlap in terms of pathological protein and the affected brain areas (for example,presence of Lewy bodies does not exclude possibility of a taupopathy). Differentiating cognitive disorders is often a serious challenge, but our diagnostic knowledge has grown enormously in recent decades.