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150-444: Alzheimer's disease ( AD ) is a neurodegenerative disease that usually starts slowly and progressively worsens, and is the cause of 60–70% of cases of dementia . 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

300-442: A polyglutamine (polyQ) tract . Diseases associated with such mutations are known as trinucleotide repeat disorders . Polyglutamine repeats typically cause dominant pathogenesis. Extra glutamine residues can acquire toxic properties through a variety of ways, including irregular protein folding and degradation pathways, altered subcellular localization, and abnormal interactions with other cellular proteins. PolyQ studies often use

450-404: A proteolytic process which causes APP to be divided into smaller fragments. Although commonly researched as neuronal proteins, APP and its processing enzymes are abundantly expressed by other brain cells. One of these fragments gives rise to fibrils of amyloid beta, which then form clumps that deposit outside neurons in dense formations known as amyloid plaques. Excitatory neurons are known to be

600-430: A conflation of many criteria: clinical signs and symptoms, evaluations of the eye, electroencephalograms (EEG), and brain magnetic resonance imaging (MRI) results. The diagnosis provided by these results are corroborated by genetic and biochemical testing. No effective treatments were available to prevent the disease from being widespread before the past few years. In recent years, more models have been created to expedite

750-468: A consequence of aging, the brains of people with Alzheimer's disease have a greater number of them in specific brain regions such as the temporal lobe . Lewy bodies are not rare in the brains of people with Alzheimer's disease. Alzheimer's disease has been identified as a protein misfolding disease , a proteopathy , caused by the accumulation of abnormally folded amyloid beta protein into amyloid plaques, and tau protein into neurofibrillary tangles in

900-452: A decline from a prior level of function and the diagnosis requires ruling out other common causes of neurocognitive decline. Advanced medical imaging with computed tomography (CT) or magnetic resonance imaging (MRI), and with single-photon emission computed tomography (SPECT) or positron emission tomography (PET), can be used to help exclude other cerebral pathology or subtypes of dementia. On MRI or CT, Alzheimer's disease usually shows

1050-451: A fifth of consumed oxygen, and reactive oxygen species produced by oxidative metabolism are a major source of DNA damage in the brain . Damage to a cell's DNA is particularly harmful because DNA is the blueprint for protein production and unlike other molecules it cannot simply be replaced by re-synthesis. The vulnerability of post-mitotic neurons to DNA damage (such as oxidative lesions or certain types of DNA strand breaks), coupled with

1200-465: A following in America , scientists such as Wilhelm Wundt , Herman Ebbinghaus , Mary Whiton Calkins , and William James would offer their contributions to the study of human cognition. Wilhelm Wundt (1832–1920) emphasized the notion of what he called introspection : examining the inner feelings of an individual. With introspection, the subject had to be careful with describing their feelings in

1350-425: A fragment from a larger protein called amyloid precursor protein (APP), a transmembrane protein that penetrates through the neuron's membrane. APP appears to play roles in normal neuron growth, survival and post-injury repair. APP is cleaved into smaller fragments by enzymes such as gamma secretase and beta secretase . One of these fragments gives rise to fibrils of amyloid beta which can self-assemble into

1500-440: A functional disability not from another disorder. The NIA-AA criteria are used mainly in research rather than in clinical assessments. They define AD through three major stages: preclinical, mild cognitive impairment (MCI), and Alzheimer's dementia. Diagnosis in the preclinical stage is complex and focuses on asymptomatic individuals; the latter two stages describe individuals experiencing symptoms. The core clinical criteria for MCI

1650-437: A functional disability that is not from another disorder, are present. Otherwise, possible AD can be diagnosed as the diagnosis follows an atypical route. For mild neurocognitive disorder due to AD, probable Alzheimer's disease can be diagnosed if there is genetic evidence, whereas possible AD can be met if all of the following are present: no genetic evidence, decline in both learning and memory, two or more cognitive deficits, and

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1800-403: A generalized or focal cortical atrophy, which may be asymmetric. Atrophy of the hippocampus is also commonly seen. Brain imaging commonly also shows cerebrovascular disease, most commonly previous strokes (small or large territory strokes), and this is thought to be a contributing cause of many cases of dementia (up to 46% cases of dementia also have cerebrovascular disease on imaging). FDG-PET scan

1950-939: A gradual decline in the activities of repair mechanisms , could lead to accumulation of DNA damage with age and contribute to brain aging and neurodegeneration. DNA single-strand breaks are common and are associated with the neurodegenerative disease ataxia- oculomotor apraxia . Increased oxidative DNA damage in the brain is associated with Alzheimer's disease and Parkinson's disease . Defective DNA repair has been linked to neurodegenerative disorders such as Alzheimer's disease, amyotrophic lateral sclerosis , ataxia telangiectasia , Cockayne syndrome , Parkinson's disease and xeroderma pigmentosum . Axonal swelling, and axonal spheroids have been observed in many different neurodegenerative diseases. This suggests that defective axons are not only present in diseased neurons, but also that they may cause certain pathological insult due to accumulation of organelles. Axonal transport can be disrupted by

2100-408: A large scale study conducted on 6,245,282 patients has shown an increased risk of developing Alzheimer's disease following COVID-19 infection in cognitively normal individuals over 65. Alzheimer's disease is characterised by loss of neurons and synapses in the cerebral cortex and certain subcortical regions. This loss results in gross atrophy of the affected regions, including degeneration in

2250-431: A mechanism of cell death in brain cells affected with tau tangles. Exactly how disturbances of production and aggregation of the beta-amyloid peptide give rise to the pathology of Alzheimer's 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

2400-825: A memory-related or non-memory-related cognitive dysfunction. In possible AD dementia, another causal disease such as cerebrovascular disease is present. Neuropsychological tests including cognitive tests such as the mini–mental state examination (MMSE), the Montreal Cognitive Assessment (MoCA) and the Mini-Cog are widely used to aid in diagnosis of the cognitive impairments in AD. These tests may not always be accurate, as they lack sensitivity to mild cognitive impairment, and can be biased by language or attention problems; more comprehensive test arrays are necessary for high reliability of results, particularly in

2550-463: A number of variables that may have affected his ability to learn and recall the non-words he created. One of the reasons, he concluded, was the amount of time between the presentation of the list of stimuli and the recitation or recall of the same. Ebbinghaus was the first to record and plot a " learning curve " and a " forgetting curve ". His work heavily influenced the study of serial position and its effect on memory Mary Whiton Calkins (1863–1930)

2700-442: 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 cause of Alzheimer's disease is poorly understood. There are many environmental and genetic risk factors associated with its development. The strongest genetic risk factor

2850-401: A philosophical approach to the study of cognition and the mind, with his Meditations he wanted people to meditate along with him to come to the same conclusions as he did but in their own free cognition. In psychology , the term "cognition" is usually used within an information processing view of an individual's psychological functions , and such is the same in cognitive engineering . In

3000-561: A reaction termed transamidation or crosslinking . Transglutaminase binding of these proteins and peptides make them clump together. The resulting structures are turned extremely resistant to chemical and mechanical disruption. Most relevant human neurodegenerative diseases share the property of having abnormal structures made up of proteins and peptides . Each of these neurodegenerative diseases have one (or several) specific main protein or peptide. In Alzheimer's disease , these are amyloid-beta and tau . In Parkinson's disease, it

3150-535: A role in the pathology of Alzheimer's disease. Inflammation is a general marker of tissue damage in any disease, and may be either secondary to tissue damage in Alzheimer's 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

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3300-469: A role in this disease mechanism. Impaired axonal transport of alpha-synuclein may also lead to its accumulation in Lewy bodies. Experiments have revealed reduced transport rates of both wild-type and two familial Parkinson's disease-associated mutant alpha-synucleins through axons of cultured neurons. Membrane damage by alpha-synuclein could be another Parkinson's disease mechanism. The main known risk factor

3450-399: A spectrum based on the degree of inflammation, a majority of patients experience early relapsing and remitting episodes of neuronal deterioration following a period of recovery. Some of these individuals may transition to a more linear progression of the disease, while about 15% of others begin with a progressive course on the onset of multiple sclerosis. The inflammatory response contributes to

3600-516: A subset of patients with familial ALS. More recently, TAR DNA-binding protein 43 (TDP-43) and Fused in Sarcoma (FUS) protein aggregates have been implicated in some cases of the disease, and a mutation in chromosome 9 ( C9orf72 ) is thought to be the most common known cause of sporadic ALS. Early diagnosis of ALS is harder than with other neurodegenerative diseases as there are no highly effective means of determining its early onset. Currently, there

3750-591: A variety of animal models because there is such a clearly defined trigger – repeat expansion. Extensive research has been done using the models of nematode ( C. elegans ), and fruit fly ( Drosophila ), mice, and non-human primates. Nine inherited neurodegenerative diseases are caused by the expansion of the CAG trinucleotide and polyQ tract, including Huntington's disease and the spinocerebellar ataxias . The presence of epigenetic modifications for certain genes has been demonstrated in this type of pathology. An example

3900-690: A variety of mechanisms including damage to: kinesin and cytoplasmic dynein , microtubules , cargoes, and mitochondria . When axonal transport is severely disrupted a degenerative pathway known as Wallerian-like degeneration is often triggered. Programmed cell death (PCD) is death of a cell in any form, mediated by an intracellular program. This process can be activated in neurodegenerative diseases including Parkinson's disease, amytrophic lateral sclerosis, Alzheimer's disease and Huntington's disease. PCD observed in neurodegenerative diseases may be directly pathogenic; alternatively, PCD may occur in response to other injury or disease processes. Apoptosis

4050-557: Is APOEε4 . APOEε4 is one of four alleles of apolipoprotein E (APOE). APOE plays a major role in lipid-binding proteins in lipoprotein particles and the ε4 allele disrupts this function. Between 40% and 80% of people with Alzheimer's disease possess at least one APOEε4 allele. The APOEε4 allele increases the risk of the disease by three times in heterozygotes and by 15 times in homozygotes . Like many human diseases, environmental effects and genetic modifiers result in incomplete penetrance . For example, Nigerian Yoruba people do not show

4200-491: Is FKBP5 gene, which progressively increases its expression with age and has been related to Braak staging and increased tau pathology both in vitro and in mouse models of AD. Several neurodegenerative diseases are classified as proteopathies as they are associated with the aggregation of misfolded proteins . Protein toxicity is one of the key mechanisms of many neurodegenrative diseases. Parkinson's disease and Huntington's disease are both late-onset and associated with

4350-777: Is aging . Mitochondrial DNA mutations as well as oxidative stress both contribute to aging. Many of these diseases are late-onset, meaning there is some factor that changes as a person ages for each disease. One constant factor is that in each disease, neurons gradually lose function as the disease progresses with age. It has been proposed that DNA damage accumulation provides the underlying causative link between aging and neurodegenerative disease. About 20–40% of healthy people between 60 and 78 years old experience discernable decrements in cognitive performance in several domains including working, spatial, and episodic memory, and processing speed. A study using electronic health records indicates that 45 (with 22 of these being replicated with

4500-573: Is alpha-synuclein . In Huntington's disease, it is huntingtin . Transglutaminase substrates : Amyloid-beta , tau , alpha-synuclein and huntingtin have been proved to be substrates of transglutaminases in vitro or in vivo, that is, they can be bonded by trasglutaminases by covalent bonds to each other and potentially to any other transglutaminase substrate in the brain. Transglutaminase augmented expression: It has been proved that in these neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, and Huntington's disease)

4650-456: Is a form of programmed cell death in multicellular organisms. It is one of the main types of programmed cell death (PCD) and involves a series of biochemical events leading to a characteristic cell morphology and death. Caspases (cysteine-aspartic acid proteases) cleave at very specific amino acid residues. There are two types of caspases: initiators and effectors . Initiator caspases cleave inactive forms of effector caspases. This activates

Alzheimer's disease - Misplaced Pages Continue

4800-438: Is a rare neurodegenerative disorder characterized by the gradual loss of both upper motor neurons (UMNs) and lower motor neurons (LMNs). Although initial symptoms may vary, most patients develop skeletal muscle weakness that progresses to involve the entire body. The precise etiology of ALS remains unknown. In 1993, missense mutations in the gene encoding the antioxidant enzyme superoxide dismutase 1 (SOD1) were discovered in

4950-479: Is a source of controversy among medical professionals. The gut microbiome might play a role in the diagnosis of PD, and research suggests various ways that could revolutionize the future of PD treatment. Huntington's disease (HD) is a rare autosomal dominant neurodegenerative disorder caused by mutations in the huntingtin gene (HTT) . HD is characterized by loss of medium spiny neurons and astrogliosis . The first brain region to be substantially affected

5100-490: Is about 90% heritable. Familial Alzheimer's disease usually implies two or more persons affected in one or more generations. Early onset familial Alzheimer's disease can be attributed to mutations in one of three genes: those encoding amyloid-beta precursor protein (APP) and presenilins PSEN1 and PSEN2 . Most mutations in the APP and presenilin genes increase the production of a small protein called amyloid beta (Aβ)42, which

5250-461: Is age. Mutations in genes such as α-synuclein (SNCA), leucine-rich repeat kinase 2 (LRRK2), glucocerebrosidase (GBA), and tau protein (MAPT) can also cause hereditary PD or increase PD risk. While PD is the second most common neurodegenerative disorder, problems with diagnoses still persist. Problems with the sense of smell is a widespread symptom of Parkinson's disease (PD), however, some neurologists question its efficacy. This assessment method

5400-676: Is an important aspect of metacognition. Aerobic and anaerobic exercise have been studied concerning cognitive improvement. There appear to be short-term increases in attention span, verbal and visual memory in some studies. However, the effects are transient and diminish over time, after cessation of the physical activity. People with Parkinson's disease has also seen improved cognition while cycling, while pairing it with other cognitive tasks. Studies evaluating phytoestrogen , blueberry supplementation and antioxidants showed minor increases in cognitive function after supplementation but no significant effects compared to placebo . Another study on

5550-527: Is available and can be examined histologically for senile plaques and neurofibrillary tangles. There are three sets of criteria for the clinical diagnoses of the spectrum of Alzheimer's disease: the 2013 fifth edition of the Diagnostic and Statistical Manual of Mental Disorders ( DSM-5 ); the National Institute on Aging - Alzheimer's Association (NIA-AA) definition as revised in 2011; and

5700-486: Is believed to occur when abnormal amounts of amyloid beta (Aβ), accumulating extracellularly as amyloid plaques and tau proteins , or intracellularly as neurofibrillary tangles , form in the brain, affecting neuronal functioning and connectivity, resulting in a progressive loss of brain function. This altered protein clearance ability is age-related, regulated by brain cholesterol, and associated with other neurodegenerative diseases. The cause for most Alzheimer's cases

5850-425: Is characterized by motor impairment, epilepsy , dementia , vision loss, and shortened lifespan. A loss of vision is common first sign of Batten disease. Loss of vision is typically preceded by cognitive and behavioral changes, seizures, and loss of the ability to walk. It is common for people to establish cardiac arrhythmias and difficulties eating food as the disease progresses. Batten disease diagnosis depends on

6000-419: Is closely related to the aforementioned study and conclusion of the memory experiments conducted by Hermann Ebbinghaus. William James (1842–1910) is another pivotal figure in the history of cognitive science. James was quite discontent with Wundt's emphasis on introspection and Ebbinghaus' use of nonsense stimuli. He instead chose to focus on the human learning experience in everyday life and its importance to

6150-671: Is commonly unaware of their deficits . Many times, families have difficulties in the detection of initial dementia symptoms and may not communicate accurate information to a physician. Supplemental testing can rule out other potentially treatable diagnoses and help avoid misdiagnoses. Common supplemental tests include blood tests , thyroid function tests , as well as tests to assess vitamin B12 levels, rule out neurosyphilis and rule out metabolic problems (including tests for kidney function , electrolyte levels and for diabetes ). MRI or CT scans might also be used to rule out other potential causes of

Alzheimer's disease - Misplaced Pages Continue

6300-400: Is deleterious to the cell and would eventually lead to cell death. Apart from tubular structures, alpha-synuclein can also form lipoprotein nanoparticles similar to apolipoproteins. The most common form of cell death in neurodegeneration is through the intrinsic mitochondrial apoptotic pathway. This pathway controls the activation of caspase-9 by regulating the release of cytochrome c from

6450-544: Is frequently seen as a prodromal stage of Alzheimer's disease. Amnesic MCI has a greater than 90% likelihood of being associated with Alzheimer's. In people with Alzheimer's disease, the increasing impairment of learning and memory eventually leads to a definitive diagnosis. In a small percentage, difficulties with language, executive functions, perception ( agnosia ), or execution of movements ( apraxia ) are more prominent than memory problems. Alzheimer's disease does not affect all memory capacities equally. Older memories of

6600-510: 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 characterized 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

6750-518: Is gathered through observation and conscientious experimentation. Two millennia later, the groundwork for modern concepts of cognition was laid during the Enlightenment by thinkers such as John Locke and Dugald Stewart who sought to develop a model of the mind in which ideas were acquired, remembered and manipulated. During the early nineteenth century cognitive models were developed both in philosophy —particularly by authors writing about

6900-456: Is hypothesized that defects in autophagy could be a common mechanism of neurodegeneration. PCD can also occur via non-apoptotic processes, also known as Type III or cytoplasmic cell death. For example, type III PCD might be caused by trophotoxicity, or hyperactivation of trophic factor receptors. Cytotoxins that induce PCD can cause necrosis at low concentrations, or aponecrosis (combination of apoptosis and necrosis) at higher concentrations. It

7050-404: Is known to target the hippocampus which is associated with memory , and this is responsible for the first symptoms of memory impairment. As the disease progresses so does the degree of memory impairment. The first symptoms are often mistakenly attributed to aging or stress . Detailed neuropsychological testing can reveal mild cognitive difficulties up to eight years before a person fulfills

7200-415: Is learned first still has to go through a retrieval process. This experiment focuses on human memory processes. The word superiority effect experiment presents a subject with a word, or a letter by itself, for a brief period of time, i.e. 40 ms, and they are then asked to recall the letter that was in a particular location in the word. In theory, the subject should be better able to correctly recall

7350-450: Is named after German psychiatrist and pathologist Alois Alzheimer , who first described it in 1906. Alzheimer's financial burden on society is large, with an estimated global annual cost of US$ 1   trillion. It is ranked as the seventh leading cause of death worldwide. Given the widespread impacts of Alzheimer's disease, both basic-science and health funders in many countries support Alzheimer's research at large scales. For example,

7500-558: Is not required for the diagnosis but it is sometimes used when standard testing is unclear. FDG-PET shows a bilateral, asymetric, temporal and parietal reduced activity. Advanced imaging may predict conversion from prodromal stages (mild cognitive impairment) to Alzheimer's disease. FDA-approved radiopharmaceutical diagnostic agents used in PET for Alzheimer's disease are florbetapir (2012), flutemetamol (2013), florbetaben (2014), and flortaucipir (2020). Because many insurance companies in

7650-449: Is primarily characterized by death of dopaminergic neurons in the substantia nigra , a region of the midbrain . The cause of this selective cell death is unknown. Notably, alpha-synuclein - ubiquitin complexes and aggregates are observed to accumulate in Lewy bodies within affected neurons. It is thought that defects in protein transport machinery and regulation, such as RAB1 , may play

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7800-478: Is produced by or causes the changes in proteins. Smoking is a significant Alzheimer's disease risk factor. Systemic markers of the innate immune system are risk factors for late-onset Alzheimer's disease. Exposure to air pollution may be a contributing factor to the development of Alzheimer's disease. Retrogenesis is a medical hypothesis that just as the fetus goes through a process of neurodevelopment beginning with neurulation and ending with myelination ,

7950-502: Is proposed to be due to the release of antigens such as myelin oligodendrocyte glycoprotein , myelin basic protein , and proteolipid protein , causing an autoimmune response. This sets off a cascade of signaling molecules that result in T cells, B cells, and macrophages to cross the blood-brain barrier and attack myelin on neuronal axons leading to inflammation. Further release of antigens drives subsequent degeneration causing increased inflammation. Multiple sclerosis presents itself as

8100-448: Is research being done regarding the diagnosis of ALS through upper motor neuron tests. The Penn Upper Motor Neuron Score (PUMNS) consists of 28 criteria with a score range of 0–32. A higher score indicates a higher level of burden present on the upper motor neurons. The PUMNS has proven quite effective in determining the burden that exists on upper motor neurons in affected patients. Independent research provided in vitro evidence that

8250-424: Is still mostly unknown, except for 1–2% of cases where deterministic genetic differences have been identified. Several competing hypotheses attempt to explain the underlying cause; the most predominant hypothesis is the amyloid beta (Aβ) hypothesis. The oldest hypothesis, on which most drug therapies are based, is the cholinergic hypothesis , which proposes that Alzheimer's disease is caused by reduced synthesis of

8400-401: Is still unclear exactly what combination of apoptosis, non-apoptosis, and necrosis causes different kinds of aponecrosis. Transglutaminases are human enzymes ubiquitously present in the human body and in the brain in particular. The main function of transglutaminases is bind proteins and peptides intra- and intermolecularly, by a type of covalent bonds termed isopeptide bonds , in

8550-400: Is subpar, and better methods need to be utilized for various aspects of clinical diagnoses. Alzheimer's has a 20% misdiagnosis rate. AD pathology is primarily characterized by the presence of amyloid plaques and neurofibrillary tangles . Plaques are made up of small peptides , typically 39–43 amino acids in length, called amyloid beta (also written as A-beta or Aβ). Amyloid beta is

8700-449: Is the striatum , followed by degeneration of the frontal and temporal cortices. The striatum's subthalamic nuclei send control signals to the globus pallidus , which initiates and modulates motion. The weaker signals from subthalamic nuclei thus cause reduced initiation and modulation of movement, resulting in the characteristic movements of the disorder, notably chorea . Huntington's disease presents itself later in life even though

8850-510: Is the Aβ oligomerization rather than the fibrils that may be the cause of this disease. Mice expressing this mutation have all the usual pathologies of Alzheimer's disease. The tau hypothesis proposes that tau protein abnormalities initiate the disease cascade. In this model, hyperphosphorylated tau begins to pair with other threads of tau as paired helical filaments . Eventually, they form neurofibrillary tangles inside neurons. When this occurs,

9000-400: Is the common name for a group of lysosomal storage disorders known as neuronal ceroid lipofuscinoses (NCLs) – each caused by a specific gene mutation, of which there are thirteen. Since Batten disease is quite rare, its worldwide prevalence is about 1 in every 100,000 live births. In North America, NCL3 disease (juvenile NCL) typically manifests between the ages of 4 and 7. Batten disease

9150-518: Is the main component of amyloid plaques . Some of the mutations merely alter the ratio between Aβ42 and the other major forms—particularly Aβ40—without increasing Aβ42 levels in the brain. Two other genes associated with autosomal dominant Alzheimer's disease are ABCA7 and SORL1 . Alleles in the TREM2 gene have been associated with a three to five times higher risk of developing Alzheimer's disease. A Japanese pedigree of familial Alzheimer's disease

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9300-466: Is the most common neurodegenerative disease. Even with billions of dollars being used to find a treatment for Alzheimer's disease, no effective treatments have been found. Within clinical trials stable and effective AD therapeutic strategies have a 99.5% failure rate. Reasons for this failure rate include inappropriate drug doses, invalid target and participant selection, and inadequate knowledge of pathophysiology of AD. Currently, diagnoses of Alzheimer's

9450-426: Is the time it takes for a participant to identify whether a green circle is present or not, should not change as the number of distractors increases. Conjunctive searches where the target is absent should have a longer reaction time than the conjunctive searches where the target is present. The theory is that in feature searches, it is easy to spot the target, or if it is absent, because of the difference in color between

9600-402: Is used along with identification of biomarkers, predominantly those for neuronal injury (mainly tau-related) and amyloid beta deposition. The core clinical criteria itself rests on the presence of cognitive impairment without the presence of comorbidities. The third stage is divided into probable and possible AD dementia. In probable AD dementia there is steady impairment of cognition over time and

9750-536: Is usually clinically diagnosed based on a person's medical history , observations from friends or relatives, and behavioral changes. The presence of characteristic neuropsychological changes with impairments in at least two cognitive domains that are severe enough to affect a person's functional abilities are required for the diagnosis. Domains that may be impaired include memory (most commonly impaired), language, executive function , visuospatial functioning, or other areas of cognition. The neurocognitive changes must be

9900-484: The Shared intentionality approach, the mother shares the essential sensory stimulus of the actual cognitive problem with the child. By sharing this stimulus, the mother provides a template for developing the young organism's nervous system. Recent findings in research on child cognitive development and advances in inter-brain neuroscience experiments have made the above proposition plausible. Based on them,

10050-506: The UK Biobank ) viral exposures can significantly elevate risks of neurodegenerative disease, including up to 15 years after infection. Many neurodegenerative diseases are caused by genetic mutations , most of which are located in completely unrelated genes. In many of the different diseases, the mutated gene has a common feature: a repeat of the CAG nucleotide triplet. CAG codes for the amino acid glutamine . A repeat of CAG results in

10200-563: 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 . No treatments can stop or reverse its progression, though some may temporarily improve symptoms. A healthy diet, physical activity, and social engagement are generally beneficial in aging, and may help in reducing

10350-454: The expression of the transglutaminase enzyme is increased. Presence of isopeptide bonds in these structures: The presence of isopeptide bonds (the result of the transglutaminase reaction) have been detected in the abnormal structures that are characteristic of these neurodegenerative diseases . Co-localization: Co-localization of transglutaminase mediated isopeptide bonds with these abnormal structures has been detected in

10500-466: The hippocampus . However, Alzheimer's disease may occur without neurofibrillary tangles in the neocortex . Plaques are dense, mostly insoluble deposits of beta-amyloid peptide and cellular material outside and around neurons . Neurofibrillary tangles are aggregates of the microtubule-associated protein tau which has become hyperphosphorylated and accumulate inside the cells themselves. Although many older individuals develop some plaques and tangles as

10650-606: The microtubules disintegrate, destroying the structure of the cell's cytoskeleton which collapses the neuron's transport system. A number of studies connect the misfolded amyloid beta and tau proteins associated with the pathology of Alzheimer's disease, as bringing about oxidative stress that leads to neuroinflammation . This chronic inflammation is also a feature of other neurodegenerative diseases including Parkinson's disease , and ALS . Spirochete infections have also been linked to dementia. DNA damages accumulate in Alzheimer's diseased brains; reactive oxygen species may be

10800-573: The mitochondrial intermembrane space . Reactive oxygen species (ROS) are normal byproducts of mitochondrial respiratory chain activity. ROS concentration is mediated by mitochondrial antioxidants such as manganese superoxide dismutase (SOD2) and glutathione peroxidase . Over production of ROS ( oxidative stress ) is a central feature of all neurodegenerative disorders. In addition to the generation of ROS, mitochondria are also involved with life-sustaining functions including calcium homeostasis, PCD, mitochondrial fission and fusion , lipid concentration of

10950-509: The philosophy of mind —and within medicine , especially by physicians seeking to understand how to cure madness. In Britain , these models were studied in the academy by scholars such as James Sully at University College London , and they were even used by politicians when considering the national Elementary Education Act 1870 ( 33 & 34 Vict. c. 75). As psychology emerged as a burgeoning field of study in Europe , whilst also gaining

11100-418: The psychological construct of Shared intentionality , highlighting its contribution to cognitive development from birth. This primary interaction provides unaware collaboration in mother-child dyads for environmental learning. Later, Igor Val Danilov developed this notion, expanding it to the intrauterine period and clarifying the neurophysiological processes underlying Shared intentionality . According to

11250-712: The shared intentionality hypothesis introduced the notion of pre-perceptual communication in the mother-fetus communication model due to nonlocal neuronal coupling. This nonlocal coupling model refers to communication between two organisms through the copying of the adequate ecological dynamics by biological systems indwelling one environmental context, where a naive actor (Fetus) replicates information from an experienced actor (Mother) due to intrinsic processes of these dynamic systems ( embodied information ) but without interacting through sensory signals. The Mother's heartbeats (a low-frequency oscillator) modulate relevant local neuronal networks in specific subsystems of both her and

11400-614: The temporal lobe and parietal lobe , and parts of the frontal cortex and cingulate gyrus . Degeneration is also present in brainstem nuclei particularly the locus coeruleus in the pons . Studies using MRI and PET have documented reductions in the size of specific brain regions in people with Alzheimer's disease as they progressed from mild cognitive impairment to Alzheimer's disease, and in comparison with similar images from healthy older adults. Both Aβ plaques and neurofibrillary tangles are clearly visible by microscopy in brains of those with Alzheimer's disease, especially in

11550-468: The 15th century, where it meant " thinking and awareness". The term comes from the Latin noun cognitio ('examination', 'learning', or 'knowledge'), derived from the verb cognosco , a compound of con ('with') and gnōscō ('know'). The latter half, gnōscō , itself is a cognate of a Greek verb, gi(g)nósko ( γι(γ)νώσκω , 'I know,' or 'perceive'). Despite

11700-611: The International Working Group criteria as revised in 2010. Three broad time periods, which can span decades, define the progression of Alzheimer's disease from the preclinical phase, to mild cognitive impairment (MCI), followed by Alzheimer's disease dementia. Eight intellectual domains are most commonly impaired in AD— memory , language , perceptual skills , attention , motor skills , orientation , problem solving and executive functional abilities, as listed in

11850-746: The US National Institutes of Health program for Alzheimer's research, the National Plan to Address Alzheimer’s Disease, has a budget of US$ 3.98 billion for fiscal year 2026. In the European Union , the 2020 Horizon Europe research programme awarded over €570 million for dementia-related projects. The course of Alzheimer's is generally described in three stages, with a progressive pattern of cognitive and functional impairment . The three stages are described as early or mild, middle or moderate, and late or severe. The disease

12000-530: The United States do not cover this procedure, its use in clinical practice is largely limited to clinical trials as of 2018. Assessment of intellectual functioning including memory testing can further characterise the state of the disease. Medical organizations have created diagnostic criteria to ease and standardise the diagnostic process for practising physicians. Definitive diagnosis can only be confirmed with post-mortem evaluations when brain material

12150-723: The accumulation of intracellular toxic proteins. Diseases caused by the aggregation of proteins are known as proteopathies , and they are primarily caused by aggregates in the following structures: There are two main avenues eukaryotic cells use to remove troublesome proteins or organelles: Damage to the membranes of organelles by monomeric or oligomeric proteins could also contribute to these diseases. Alpha-synuclein can damage membranes by inducing membrane curvature, and cause extensive tubulation and vesiculation when incubated with artificial phospholipid vesicles. The tubes formed from these lipid vesicles consist of both micellar as well as bilayer tubes. Extensive induction of membrane curvature

12300-455: The acquisition and development of cognitive capabilities. Human cognition is conscious and unconscious , concrete or abstract , as well as intuitive (like knowledge of a language) and conceptual (like a model of a language). It encompasses processes such as memory , association , concept formation , pattern recognition , language , attention , perception , action , problem solving , and mental imagery . Traditionally, emotion

12450-502: The autopsy of brains of patients with these diseases. The process of neurodegeneration is not well understood, so the diseases that stem from it have, as yet, no cures. In the search for effective treatments (as opposed to palliative care ), investigators employ animal models of disease to test potential therapeutic agents. Model organisms provide an inexpensive and relatively quick means to perform two main functions: target identification and target validation. Together, these help show

12600-420: The beginning of cognition is memory storage about the relevant ecological dynamics by the naive nervous system (i.e., memorizing the ecological condition of relevant sensory stimulus) at the molecular level – an engram . Evidence derived using optical imaging , molecular-genetic and optogenetic techniques in conjunction with appropriate behavioural analyses continues to offer support for the idea that changing

12750-451: The beginning of the sequence, called the primacy effect , and information at the end of the sequence, called the recency effect . Consequently, information given in the middle of the sequence is typically forgotten, or not recalled as easily. This study predicts that the recency effect is stronger than the primacy effect, because the information that is most recently learned is still in working memory when asked to be recalled. Information that

12900-431: The brain. Late-onset Alzheimer's is about 70% heritable . Genetic models in 2020 predict Alzheimer's disease with 90% accuracy. Most cases of Alzheimer's are not familial , and so they are termed sporadic Alzheimer's disease. Of the cases of sporadic Alzheimer's disease, most are classified as late onset where they are developed after the age of 65 years. The strongest genetic risk factor for sporadic Alzheimer's disease

13050-402: The brain. Plaques are made up of small peptides , 39–43  amino acids in length, called amyloid beta. Amyloid beta is a fragment from the larger amyloid-beta precursor protein (APP) a transmembrane protein that penetrates the cell's membrane . APP is critical to neuron growth, survival, and post-injury repair. In Alzheimer's disease, gamma secretase and beta secretase act together in

13200-924: The brains of people with Alzheimer's disease go through a reverse neurodegeneration process starting with demyelination and death of axons (white matter) and ending with the death of grey matter. Likewise the hypothesis is, that as infants go through states of cognitive development , people with Alzheimer's disease go through the reverse process of progressive cognitive impairment . According to one theory, dysfunction of oligodendrocytes and their associated myelin during aging contributes to axon damage, which in turn generates in amyloid production and tau hyperphosphorylation . An in vivo study employing genetic mouse models to simulate myelin dysfunction and amyloidosis further reveal that age-related myelin degradation increases sites of Aβ production and distracts microglia from Aβ plaques, with both mechanisms dually exacerbating amyloidosis. Additionally, comorbidities between

13350-521: The cell to the ends of the axon and back. A protein called tau stabilises the microtubules when phosphorylated , and is therefore called a microtubule-associated protein . In Alzheimer's disease, tau undergoes chemical changes, becoming hyperphosphorylated; it then begins to pair with other threads, creating neurofibrillary tangles and disintegrating the neuron's transport system. Pathogenic tau can also cause neuronal death through transposable element dysregulation. Necroptosis has also been reported as

13500-536: The clinical criteria for diagnosis of Alzheimer's disease. These early symptoms can affect the most complex activities of daily living . The most noticeable deficit is short term memory loss, which shows up as difficulty in remembering recently learned facts and inability to acquire new information. Subtle problems with the executive functions of attentiveness , planning , flexibility, and abstract thinking , or impairments in semantic memory (memory of meanings, and concept relationships) can also be symptomatic of

13650-410: The construction of human thought or mental processes. Jean Piaget was one of the most important and influential people in the field of developmental psychology . He believed that humans are unique in comparison to animals because we have the capacity to do "abstract symbolic reasoning". His work can be compared to Lev Vygotsky , Sigmund Freud , and Erik Erikson who were also great contributors in

13800-407: The construction of human thought or mental processes. Research shows the intentional engagement of fetuses with the environment, demonstrating cognitive achievements. However, organisms with simple reflexes cannot cognize the environment alone because the environment is the cacophony of stimuli (electromagnetic waves, chemical interactions, and pressure fluctuations). Their sensation is too limited by

13950-473: The demyelinating disease, multiple sclerosis , and Alzheimer's disease have been reported. The association with celiac disease is unclear, with a 2019 study finding no increase in dementia overall in those with celiac disease while a 2018 review found an association with several types of dementia including Alzheimer's disease. Studies have shown a potential link between infection with certain viruses and developing Alzheimer's disease later in life. Notably,

14100-496: The dense extracellular amyloid plaques. Parkinson's disease (PD) is the second most common neurodegenerative disorder. It typically manifests as bradykinesia , rigidity, resting tremor and posture instability. The crude prevalence rate of PD has been reported to range from 15 per 100,000 to 12,500 per 100,000, and the incidence of PD from 15 per 100,000 to 328 per 100,000, with the disease being less common in Asian countries. PD

14250-716: The disciplines of cognitive science . Metacognition is an awareness of one's thought processes and an understanding of the patterns behind them. The term comes from the root word meta , meaning "beyond", or "on top of". Metacognition can take many forms, such as reflecting on one's ways of thinking, and knowing when and how oneself and others use particular strategies for problem-solving . There are generally two components of metacognition: (1) cognitive conceptions and (2) cognitive regulation system. Research has shown that both components of metacognition play key roles in metaconceptual knowledge and learning. Metamemory , defined as knowing about memory and mnemonic strategies,

14400-489: The disease. Multiple sclerosis (MS) is a chronic debilitating demyelinating disease of the central nervous system , caused by an autoimmune attack resulting in the progressive loss of myelin sheath on neuronal axons. The resultant decrease in the speed of signal transduction leads to a loss of functionality that includes both cognitive and motor impairment depending on the location of the lesion. The progression of MS occurs due to episodes of increasing inflammation, which

14550-498: The distractor task, they are asked to recall the trigram from before the distractor task. In theory, the longer the distractor task, the harder it will be for participants to correctly recall the trigram. This experiment focuses on human short-term memory . During the memory span experiment , each subject is presented with a sequence of stimuli of the same kind; words depicting objects, numbers, letters that sound similar, and letters that sound dissimilar. After being presented with

14700-550: 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 Alzheimer's disease. Alzheimer's disease (AD) can only be definitively diagnosed with autopsy findings; in the absence of autopsy, clinical diagnoses of AD are "possible" or "probable", based on other findings. Up to 23% of those clinically diagnosed with AD may be misdiagnosed and may have pathology suggestive of another condition with symptoms that mimic those of AD. AD

14850-429: The earliest stages of the disease. Further neurological examinations are crucial in the differential diagnosis of Alzheimer's disease and other diseases. Interviews with family members are used in assessment; caregivers can supply important information on daily living abilities and on the decrease in the person's mental function . A caregiver's viewpoint is particularly important, since a person with Alzheimer's disease

15000-420: The early stages of Alzheimer's disease. Apathy and depression can be seen at this stage, with apathy remaining as the most persistent symptom throughout the course of the disease. Mild cognitive impairment (MCI) is often found to be a transitional stage between normal aging and dementia . MCI can present with a variety of symptoms, and when memory loss is the predominant symptom, it is termed amnestic MCI and

15150-410: The effectors that in turn cleave other proteins resulting in apoptotic initiation. Autophagy is a form of intracellular phagocytosis in which a cell actively consumes damaged organelles or misfolded proteins by encapsulating them into an autophagosome , which fuses with a lysosome to destroy the contents of the autophagosome. Because many neurodegenerative diseases show unusual protein aggregates, it

15300-402: The effects of herbal and dietary supplements on cognition in menopause show that soy and Ginkgo biloba supplementation could improve women's cognition. Exposing individuals with cognitive impairment (i.e. dementia ) to daily activities designed to stimulate thinking and memory in a social setting, seems to improve cognition. Although study materials are small, and larger studies need to confirm

15450-460: The fact that people with trisomy 21 (Down syndrome) who have an extra gene copy almost universally exhibit at least the earliest symptoms of Alzheimer's disease by 40 years of age. A specific isoform of apolipoprotein, APOE4 , is a major genetic risk factor for Alzheimer's disease. While apolipoproteins enhance the breakdown of beta amyloid, some isoforms are not very effective at this task (such as APOE4), leading to excess amyloid buildup in

15600-488: The field of developmental psychology. Piaget is known for studying the cognitive development in children, having studied his own three children and their intellectual development, from which he would come to a theory of cognitive development that describes the developmental stages of childhood. Studies on cognitive development have also been conducted in children beginning from the embryonal period to understand when cognition appears and what environmental attributes stimulate

15750-439: The fields of linguistics , musicology , anesthesia , neuroscience , psychiatry , psychology , education , philosophy , anthropology , biology , systemics , logic , and computer science . These and other approaches to the analysis of cognition (such as embodied cognition ) are synthesized in the developing field of cognitive science , a progressively autonomous academic discipline . The word cognition dates back to

15900-539: The fourth text revision of the DSM (DSM-IV-TR). The DSM-5 defines criteria for probable or possible AD for both major and mild neurocognitive disorder. Major or mild neurocognitive disorder must be present along with at least one cognitive deficit for a diagnosis of either probable or possible AD. For major neurocognitive disorder due to AD, probable Alzheimer's disease can be diagnosed if the individual has genetic evidence of AD or if two or more acquired cognitive deficits, and

16050-475: The function and capacity of human memory. Ebbinghaus developed his own experiment in which he constructed over 2,000 syllables made out of nonexistent words (for instance, 'EAS'). He then examined his own personal ability to learn these non-words. He purposely chose non-words as opposed to real words to control for the influence of pre-existing experience on what the words might symbolize, thus enabling easier recollection of them. Ebbinghaus observed and hypothesized

16200-506: The letter when it was presented in a word than when it was presented in isolation. This experiment focuses on human speech and language. In the Brown–Peterson cohomology experiment , participants are briefly presented with a trigram and in one particular version of the experiment, they are then given a distractor task, asking them to identify whether a sequence of words is in fact words, or non-words (due to being misspelled, etc.). After

16350-526: The loss of the grey matter, and as a result current literature devotes itself to combatting the auto-inflammatory aspect of the disease. While there are several proposed causal links between EBV and the HLA-DRB1*15:01 allele to the onset of MS – they may contribute to the degree of autoimmune attack and the resultant inflammation – they do not determine the onset of MS. Amyotrophic lateral sclerosis (ALS), commonly referred to Lou Gehrig's disease,

16500-400: The major producers of amyloid beta that contribute to major extracellular plaque deposition. Alzheimer's disease is also considered a tauopathy due to abnormal aggregation of the tau protein . Every neuron has a cytoskeleton , an internal support structure partly made up of structures called microtubules . These microtubules act like tracks, guiding nutrients and molecules from the body of

16650-471: The major source of this DNA damage. Sleep disturbances are seen as a possible risk factor for inflammation in Alzheimer's disease. Sleep disruption was previously only seen as a consequence of Alzheimer's disease, but as of 2020, accumulating evidence suggests that this relationship may be bidirectional . The cellular homeostasis of biometals such as ionic copper, iron, and zinc is disrupted in Alzheimer's disease, though it remains unclear whether this

16800-404: The mind. The development of Cognitive psychology arose as psychology from different theories, and so began exploring these dynamics concerning mind and environment, starting a movement from these prior dualist paradigms that prioritized cognition as systematic computation or exclusively behavior. For years, sociologists and psychologists have conducted studies on cognitive development , i.e.

16950-714: The mitochondrial membranes, and the mitochondrial permeability transition. Mitochondrial disease leading to neurodegeneration is likely, at least on some level, to involve all of these functions. There is strong evidence that mitochondrial dysfunction and oxidative stress play a causal role in neurodegenerative disease pathogenesis, including in four of the more well known diseases Alzheimer's , Parkinson's , Huntington's , and amyotrophic lateral sclerosis . Neurons are particularly vulnerable to oxidative damage due to their strong metabolic activity associated with high transcription levels, high oxygen consumption, and weak antioxidant defense. The brain metabolizes as much as

17100-488: The most cognitively demanding activities. 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 Alzheimer's disease progresses, so

17250-411: The most objective manner possible in order for Wundt to find the information scientific. Though Wundt's contributions are by no means minimal, modern psychologists find his methods to be too subjective and choose to rely on more objective procedures of experimentation to make conclusions about the human cognitive process. Hermann Ebbinghaus (1850–1909) conducted cognitive studies that mainly examined

17400-514: The nervous system of the fetus due to the effect of the interference of the low-frequency oscillator (Mother heartbeats) and already exhibited gamma activity in these neuronal networks (interference in physics is the combination of two or more electromagnetic waveforms to form a resultant wave). Therefore, the subliminal perception in a fetus emerges due to Shared intentionality with the mother that stimulates cognition in this organism even before birth. Another crucial question in understanding

17550-766: The neuronal death that is responsible for the symptoms of Alzheimer's disease. Cognitive Cognition is the "mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception , attention , thought , imagination , intelligence , the formation of knowledge , memory and working memory , judgment and evaluation , reasoning and computation , problem-solving and decision-making , comprehension and production of language . Cognitive processes use existing knowledge to discover new knowledge. Cognitive processes are analyzed from different perspectives within different contexts, notably in

17700-441: The neurotransmitter acetylcholine . The loss of cholinergic neurons noted in the limbic system and cerebral cortex, is a key feature in the progression of Alzheimer's. The 1991 amyloid hypothesis postulated that extracellular amyloid beta (Aβ) deposits are the fundamental cause of the disease. Support for this postulate comes from the location of the gene for the amyloid precursor protein (APP) on chromosome 21 , together with

17850-456: The noise to solve the cue problem–the relevant stimulus cannot overcome the noise magnitude if it passes through the senses (see the binding problem ). Fetuses need external help to stimulate their nervous system in choosing the relevant sensory stimulus for grasping the perception of objects. The Shared intentionality approach proposes a plausible explanation of perception development in this earlier stage. Initially, Michael Tomasello introduced

18000-783: The oldest paradigms is the leveling and sharpening of stories as they are repeated from memory studied by Bartlett . The semantic differential used factor analysis to determine the main meanings of words, finding that the ethical value of words is the first factor. More controlled experiments examine the categorical relationships of words in free recall . The hierarchical structure of words has been explicitly mapped in George Miller 's WordNet . More dynamic models of semantic networks have been created and tested with computational systems such as neural networks , latent semantic analysis (LSA), Bayesian analysis , and multidimensional factor analysis. The meanings of words are studied by all

18150-575: The person from home care to other long-term care facilities . During the final stage, known as the late-stage or severe stage, there is complete dependence on caregivers. Language is reduced to simple phrases or even single words, eventually leading to complete loss of speech. Despite the loss of verbal language abilities, people can often understand and return emotional signals. Although aggressiveness can still be present, extreme apathy and exhaustion are much more common symptoms. People with Alzheimer's disease will ultimately not be able to perform even

18300-453: The person with Alzheimer's 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; however, they are commonly unnoticed. As the disease progresses, people with Alzheimer's disease can often continue to perform many tasks independently; however, they may need assistance or supervision with

18450-446: The person's 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,

18600-653: The pivotal CONNECTION trial of patients with mild-to-moderate disease. With CONCERT, the remaining Pfizer and Medivation Phase III trial for Dimebon (latrepirdine) in Alzheimer's disease failed in 2012, effectively ending the development in this indication. In another experiment using a rat model of Alzheimer's disease, it was demonstrated that systemic administration of hypothalamic proline-rich peptide (PRP)-1 offers neuroprotective effects and can prevent neurodegeneration in hippocampus amyloid-beta 25–35. This suggests that there could be therapeutic value to PRP-1. Protein degradation offers therapeutic options both in preventing

18750-441: The primary cellular sites where SOD1 mutations act are located on astrocytes . Astrocytes then cause the toxic effects on the motor neurons . The specific mechanism of toxicity still needs to be investigated, but the findings are significant because they implicate cells other than neuron cells in neurodegeneration. Batten disease is a rare and fatal recessive neurodegenerative disorder that begins in childhood. Batten disease

18900-686: The proteins that cause the disease works towards manifestation from their early stages in the humans affected by the proteins. Along with being a neurodegenerative disorder, HD has links to problems with neurodevelopment. HD is caused by polyglutamine tract expansion in the huntingtin gene, resulting in the mutant huntingtin. Aggregates of mutant huntingtin form as inclusion bodies in neurons, and may be directly toxic. Additionally, they may damage molecular motors and microtubules to interfere with normal axonal transport , leading to impaired transport of important cargoes such as BDNF . Huntington's disease currently has no effective treatments that would modify

19050-515: The relationship between dose of APOEε4 and incidence or age-of-onset for Alzheimer's disease seen in other human populations. Only 1–2% of Alzheimer's cases are inherited due to autosomal dominant effects, as Alzheimer's is highly polygenic. When the disease is caused by autosomal dominant variants, it is known as early onset familial Alzheimer's disease , which is rarer and has a faster rate of progression. Less than 5% of sporadic Alzheimer's disease have an earlier onset, and early-onset Alzheimer's

19200-507: The research process for methods to treat Batten disease. Creutzfeldt–Jakob disease (CJD) is a prion disease that is characterized by rapidly progressive dementia. Misfolded proteins called prions aggregate in brain tissue leading to nerve cell death. Variant Creutzfeldt–Jakob disease (vCJD) is the infectious form that comes from the meat of a cow that was infected with bovine spongiform encephalopathy , also called mad cow disease. The greatest risk factor for neurodegenerative diseases

19350-484: The results, the effect of social cognitive stimulation seems to be larger than the effects of some drug treatments. Transcranial magnetic stimulation (TMS) has been shown to improve cognition in individuals without dementia 1 month after treatment session compared to before treatment. The effect was not significantly larger compared to placebo. Computerized cognitive training, utilizing a computer based training regime for different cognitive functions has been examined in

19500-832: The risk of cognitive decline and Alzheimer's. Affected people become increasingly reliant on others for assistance, often placing a burden on caregivers . The pressures can include social, psychological, physical, and economic elements. Exercise programs may be beneficial with respect to activities of daily living and can potentially improve outcomes. Behavioral problems or psychosis due to dementia are sometimes treated with antipsychotics , but this has an increased risk of early death. As of 2020, there were approximately 50 million people worldwide with Alzheimer's disease. It most often begins in people over 65 years of age, although up to 10% of cases are early-onset impacting those in their 30s to mid-60s. It affects about 6% of people 65 years and older, and women more often than men. The disease

19650-801: The risk of falling increases. During this phase, memory problems worsen, and the person may fail to recognise close relatives. Long-term memory , which was previously intact, becomes impaired. Behavioral and neuropsychiatric changes become more prevalent. Common manifestations are wandering , irritability and emotional lability , leading to crying, outbursts of unpremeditated aggression , or resistance to caregiving. Sundowning can also appear. Approximately 30% of people with Alzheimer's disease develop illusionary misidentifications and other delusional symptoms. Subjects also lose insight of their disease process and limitations ( anosognosia ). Urinary incontinence can develop. These symptoms create stress for relatives and caregivers, which can be reduced by moving

19800-412: The same for letters that sound dissimilar and short words. The memory span is projected to be shorter with letters that sound similar and with longer words. In one version of the visual search experiment , a participant is presented with a window that displays circles and squares scattered across it. The participant is to identify whether there is a green circle on the window. In the featured search,

19950-425: The simplest tasks independently; muscle mass and mobility deteriorates to the point where they are bedridden and unable to feed themselves. The cause of death is usually an external factor, such as infection of pressure ulcers or pneumonia , not the disease itself. In some cases, there is a paradoxical lucidity immediately before death, where there is an unexpected recovery of mental clarity. Alzheimer's disease

20100-416: The specific region affected, ranging from issues related to movement to the development of dementia. Alzheimer's disease (AD) is a chronic neurodegenerative disease that results in the loss of neurons and synapses in the cerebral cortex and certain subcortical structures, resulting in gross atrophy of the temporal lobe , parietal lobe , and parts of the frontal cortex and cingulate gyrus . It

20250-407: The stimuli, the subject is asked to recall the sequence of stimuli that they were given in the exact order in which it was given. In one particular version of the experiment, if the subject recalled a list correctly, the list length was increased by one for that type of material, and vice versa if it was recalled incorrectly. The theory is that people have a memory span of about seven items for numbers,

20400-448: The strength of connections between neurons is one of the major mechanisms by which engrams are stored in the brain. Two (or more) possible mechanisms of cognition can involve both quantum effects and synchronization of brain structures due to electromagnetic interference. The Serial-position effect is meant to test a theory of memory that states that when information is given in a serial manner, we tend to remember information at

20550-400: The study of social cognition , a branch of social psychology , the term is used to explain attitudes , attribution , and group dynamics . However, psychological research within the field of cognitive science has also suggested an embodied approach to understanding cognition. Contrary to the traditional computationalist approach, embodied cognition emphasizes the body's significant role in

20700-410: The study of cognition. James' most significant contribution to the study and theory of cognition was his textbook Principles of Psychology which preliminarily examines aspects of cognition such as perception, memory, reasoning, and attention. René Descartes (1596–1650) was a seventeenth-century philosopher who came up with the phrase "Cogito, ergo sum", which means "I think, therefore I am." He took

20850-414: The subject is presented with several trial windows that have blue squares or circles and one green circle or no green circle in it at all. In the conjunctive search, the subject is presented with trial windows that have blue circles or green squares and a present or absent green circle whose presence the participant is asked to identify. What is expected is that in the feature searches, reaction time, that

21000-414: The symptoms – including tumors or strokes. Delirium and depression can be common among individuals and are important to rule out. Neurodegenerative disease Within neurodegenerative diseases, it is estimated that 55 million people worldwide had dementia in 2019, and that by 2050 this figure will increase to 139 million people. The consequences of neurodegeneration can vary widely depending on

21150-550: The synthesis and degradation of irregular proteins. There is also interest in upregulating autophagy to help clear protein aggregates implicated in neurodegeneration. Both of these options involve very complex pathways that we are only beginning to understand. The goal of immunotherapy is to enhance aspects of the immune system. Both active and passive vaccinations have been proposed for Alzheimer's disease and other conditions; however, more research must be done to prove safety and efficacy in humans. A current therapeutic target for

21300-536: The target and the distractors. In conjunctive searches where the target is absent, reaction time increases because the subject has to look at each shape to determine whether it is the target or not because some of the distractors if not all of them, are the same color as the target stimuli. Conjunctive searches where the target is present take less time because if the target is found, the search between each shape stops. The semantic network of knowledge representation systems have been studied in various paradigms. One of

21450-647: The toxic form of the protein responsible for disrupting the cell's calcium ion homeostasis , induces programmed cell death ( apoptosis ). It is also known that A β selectively builds up in the mitochondria in the cells of Alzheimer's-affected brains, and it also inhibits certain enzyme functions and the utilisation of glucose by neurons. Iron dyshomeostasis is linked to disease progression, an iron-dependent form of regulated cell death called ferroptosis could be involved. Products of lipid peroxidation are also elevated in AD brain compared with controls. Various inflammatory processes and cytokines may also have

21600-416: The treatment of Alzheimer's disease is the protease β-secretase , which is involved in the amyloidogenic processing pathway that leads to the pathological accumulation of proteins in the brain. When the gene that encodes for amyloid precursor protein (APP) is spliced by α-secretase rather than β-secretase, the toxic protein β amyloid is not produced. Targeted inhibition of β-secretase can potentially prevent

21750-504: The value of any specific therapeutic strategies and drugs when attempting to ameliorate disease severity. An example is the drug Dimebon by Medivation, Inc. In 2009 this drug was in phase III clinical trials for use in Alzheimer's disease, and also phase II clinical trials for use in Huntington's disease. In March 2010, the results of a clinical trial phase III were released; the investigational Alzheimer's disease drug Dimebon failed in

21900-497: The word cognitive itself dating back to the 15th century, attention to cognitive processes came about more than eighteen centuries earlier, beginning with Aristotle (384–322 BCE) and his interest in the inner workings of the mind and how they affect the human experience. Aristotle focused on cognitive areas pertaining to memory, perception, and mental imagery. He placed great importance on ensuring that his studies were based on empirical evidence, that is, scientific information that

22050-547: Was a movement known as cognitivism in the 1950s, emerging after the Behaviorist movement viewed cognition as a form of behavior. Cognitivism approached cognition as a form of computation, viewing the mind as a machine and consciousness as an executive function. However; post cognitivism began to emerge in the 1990s as the development of cognitive science presented theories that highlighted the necessity of cognitive action as embodied, extended, and producing dynamic processes in

22200-419: Was an influential American pioneer in the realm of psychology. Her work also focused on human memory capacity. A common theory, called the recency effect , can be attributed to the studies that she conducted. The recency effect, also discussed in the subsequent experiment section, is the tendency for individuals to be able to accurately recollect the final items presented in a sequence of stimuli. Calkin's theory

22350-491: Was found to be associated with a deletion mutation of codon 693 of APP. This mutation and its association with Alzheimer's disease was first reported in 2008, and is known as the Osaka mutation. Only homozygotes with this mutation have an increased risk of developing Alzheimer's disease. This mutation accelerates Aβ oligomerization but the proteins do not form the amyloid fibrils that aggregate into amyloid plaques, suggesting that it

22500-482: Was not thought of as a cognitive process, but now much research is being undertaken to examine the cognitive psychology of emotion; research is also focused on one's awareness of one's own strategies and methods of cognition, which is called metacognition . The concept of cognition has gone through several revisions through the development of disciplines within psychology. Psychologists initially understood cognition governing human action as information processing. This

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