Neurodegenerative disease in the context of "Neurocognition"

In philosophy, the self is an individual's own being, knowledge, and values, and the relationship between these attributes.

The first-person perspective distinguishes selfhood from personal identity. Whereas "identity" is (literally) sameness and may involve categorization and labeling,selfhood implies a first-person perspective and suggests potential uniqueness. Conversely, "person" is used as a third-person reference. Personal identity can be impaired in late-stage Alzheimer's disease and in other neurodegenerative diseases. Finally, the self is distinguishable from "others". Including the distinction between sameness and otherness, the self versus other is a research topic in contemporary philosophy and contemporary phenomenology (see also psychological phenomenology), psychology, psychiatry, neurology, and neuroscience.

Alzheimer's disease (AD) is a neurodegenerative disease and is the most common form of dementia, accounting for around 60–70% of cases. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems with language, disorientation (including easily getting lost), mood swings, loss of motivation, self-neglect, and behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the average life expectancy following diagnosis is three to twelve years.

The causes of Alzheimer's disease remain poorly understood. There are many environmental and genetic risk factors associated with its development. The strongest genetic risk factor is from an allele of apolipoprotein E. Other risk factors include a history of head injury, clinical depression, and high blood pressure. The progression of the disease is largely characterised by the accumulation of malformed protein deposits in the cerebral cortex, called amyloid plaques and neurofibrillary tangles. These misfolded protein aggregates interfere with normal cell function, and over time lead to irreversible degeneration of neurons and loss of synaptic connections in the brain. A probable diagnosis is based on the history of the illness and cognitive testing, with medical imaging and blood tests to rule out other possible causes. Initial symptoms are often mistaken for normal brain aging. Examination of brain tissue is needed for a definite diagnosis, but this can only take place after death.

Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor and non-motor systems. The motor symptoms are collectively called parkinsonism and include tremors, bradykinesia (slowness in initiating movement), rigidity, and postural instability (difficulty maintaining balance). Non-motor symptoms such as dysautonomia (autonomic nervous system failures), sleep abnormalities, anosmia (decreased ability to smell), and behavioral changes or neuropsychiatric problems, such as cognitive impairment, psychosis, and anxiety, may appear at any stage of the disease. Symptoms typically develop gradually and non-motor issues become more prevalent as the disease progresses.

Most Parkinson's disease cases are idiopathic, though contributing factors have been identified. Pathophysiology involves progressive degeneration of nerve cells in the substantia nigra, a midbrain region that provides dopamine to the basal ganglia, a system involved in voluntary motor control. The cause of this cell death is poorly understood, but involves the aggregation of alpha-synuclein into Lewy bodies within neurons. Other potential factors involve genetic and environmental influences, medications, lifestyle, and prior health conditions.

Dementia is a syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform everyday activities. This typically involves problems with memory, thinking, behavior, and motor control. Aside from memory impairment and a disruption in thought patterns, the most common symptoms of dementia include emotional problems, difficulties with language, and decreased motivation. The symptoms may be described as occurring in a continuum over several stages. Dementia is a life-limiting condition, having a significant effect on the individual, their caregivers, and their social relationships in general. A diagnosis of dementia requires the observation of a change from a person's usual mental functioning and a greater cognitive decline than might be caused by the normal aging process.

Several diseases and injuries to the brain, such as a stroke, can give rise to dementia. However, the most common cause is Alzheimer's disease, a neurodegenerative disorder. Dementia is a neurocognitive disorder with varying degrees of severity (mild to major) and many forms or subtypes. Dementia is an acquired brain syndrome, marked by a decline in cognitive function, and is contrasted with neurodevelopmental disorders. It has also been described as a spectrum of disorders with subtypes of dementia based on which known disorder caused its development, such as Parkinson's disease for Parkinson's disease dementia, Huntington's disease for Huntington's disease dementia, vascular disease for vascular dementia, HIV infection causing HIV dementia, frontotemporal lobar degeneration for frontotemporal dementia, Lewy body disease for dementia with Lewy bodies, and prion diseases. Subtypes of neurodegenerative dementias may also be based on the underlying pathology of misfolded proteins, such as synucleinopathies and tauopathies. The coexistence of more than one type of dementia is known as mixed dementia.

A prion (/ˈpriːɒn/ ) is a misfolded protein that induces misfolding in normal variants of the same protein, leading to cellular death. Prions are responsible for prion diseases, known as transmissible spongiform encephalopathy (TSEs), which are fatal and transmissible neurodegenerative diseases affecting both humans and animals. These proteins can misfold sporadically, due to genetic mutations, or by exposure to an already misfolded protein, leading to an abnormal three-dimensional structure that can propagate misfolding in other proteins.

The term prion comes from "proteinaceous infectious particle". Unlike other infectious agents such as viruses, bacteria, and fungi, prions do not contain nucleic acids (DNA or RNA). Prions are mainly twisted isoforms of the major prion protein (PrP), a naturally occurring protein with an uncertain function. They are the hypothesized cause of various TSEs, including scrapie in sheep, chronic wasting disease (CWD) in deer, bovine spongiform encephalopathy (BSE) in cattle (mad cow disease), and Creutzfeldt–Jakob disease (CJD) in humans.

In excitotoxicity, nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamate become pathologically high, resulting in excessive stimulation of receptors. For example, when glutamate receptors such as NMDA receptors or AMPA receptors encounter excessive levels of the excitatory neurotransmitter, glutamate, significant neuronal damage might ensue. Different mechanisms might lead to increased extracellular glutamate concentrations, e.g. reduced uptake by glutamate transporters (EAATs), synaptic hyperactivity, or abnormal release from different neural cell types. Excess glutamate allows high levels of calcium ions (Ca) to enter the cell. Ca influx into cells activates a number of enzymes, including phospholipases, endonucleases, and proteases such as calpain. These enzymes go on to damage cell structures such as components of the cytoskeleton, membrane, and DNA. In evolved, complex adaptive systems such as biological life it must be understood that mechanisms are rarely, if ever, simplistically direct. For example, NMDA, in subtoxic amounts, can block glutamate toxicity and induce neuronal survival. In addition to abnormally high neurotransmitter concentrations, also elevation of the extracellular potassium concentration, acidification and other mechanisms may contribute to excitotoxicity.

Excitotoxicity may be involved in cancers, spinal cord injury, stroke, traumatic brain injury, hearing loss (through noise overexposure or ototoxicity), and in neurodegenerative diseases of the central nervous system such as multiple sclerosis, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), Parkinson's disease, alcoholism, alcohol withdrawal or hyperammonemia and especially over-rapid benzodiazepine withdrawal, and also Huntington's disease. Other common conditions that cause excessive glutamate concentrations around neurons are hypoglycemia. Blood sugars are the primary energy source for glutamate removal from inter-synaptic spaces at the NMDA and AMPA receptor site. Persons in excitotoxic shock must never fall into hypoglycemia. Patients should be given 5% glucose (dextrose) IV drip during excitotoxic shock to avoid a dangerous build up of glutamate. When 5% glucose (dextrose) IV drip is not available high levels of fructose are given orally. Treatment is administered during the acute stages of excitotoxic shock along with glutamate receptor antagonists. Dehydration should be avoided as this also contributes to the concentrations of glutamate in the inter-synaptic cleft and "status epilepticus can also be triggered by a build up of glutamate around inter-synaptic neurons."

Aphasia, also known as dysphasia, is an impairment in a person's ability to comprehend or formulate language because of dysfunction in specific brain regions. The major causes are stroke and head trauma; prevalence is hard to determine, but aphasia due to stroke is estimated to be 0.1–0.4% in developed countries. Aphasia can also be the result of brain tumors, epilepsy, autoimmune neurological diseases, brain infections, or neurodegenerative diseases (such as dementias).

To be diagnosed with aphasia, a person's language must be significantly impaired in one or more of the four aspects of communication. In the case of progressive aphasia, a noticeable decline in language abilities over a short period of time is required. The four aspects of communication include spoken language production, spoken language comprehension, written language production, and written language comprehension. Impairments in any of these aspects can impact functional communication.

Disorders of diminished motivation (DDM) are a group of disorders involving diminished motivation and associated emotions. Many different terms have been used to refer to diminished motivation. Often however, a spectrum is defined encompassing apathy, abulia, and akinetic mutism, with apathy the least severe and akinetic mutism the most extreme.

DDM can be caused by psychiatric disorders like depression and schizophrenia, brain injuries, strokes, and neurodegenerative diseases. Damage to the anterior cingulate cortex and to the striatum, which includes the nucleus accumbens and caudate nucleus and is part of the mesolimbic dopamine reward pathway, have been especially associated with DDM. Diminished motivation can also be induced by certain drugs, including antidopaminergic agents like antipsychotics, selective serotonin reuptake inhibitors (SSRIs), and cannabis, among others.

Neurofibrillary tangles (NFTs) are intracellular aggregates of hyperphosphorylated tau protein that are most commonly known as a primary biomarker of Alzheimer's disease. NFTs also are present in numerous other diseases known collectively as tauopathies. Little is known about their exact relationship to the different pathologies, but it is typically recognized that tauopathy is an important factor in the pathogenesis of several neurodegenerative diseases.

NFTs consist primarily of a misfolded, hyperphosphorylated microtubule-associated protein known as tau, which abnormally polymerizes into insoluble filaments within cells. Under the electron microscope, these polymers of tau are seen to take two basic forms: paired helical filaments (PHFs) and straight filaments. These basic types of tau filaments can vary structurally, especially in different tauopathies. The filaments bundle together to form the neurofibrillary tangles that are evident under the light microscope. Classical NFTs are located within the neuronal cell body, although it is now recognized that abnormal, filamentous tau occurs also in neuronal dendrites and axons (referred to as neuropil threads) and the dystrophic (abnormal) neurites that surround neuritic Abeta plaques. Mature NFTs in cell bodies can have a torch-like or globose appearance, depending on the type of neuron involved. When tangle-containing neurons die, the tangles can remain in the neuropil as extracellular "ghost tangles".