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84-500: Boston Legal follows the exploits of former Practice character Alan Shore, and his passionate co-workers, at the fictional offices of Crane, Poole & Schmidt. The high-end litigation firm, based in Boston, handles both civil and criminal law cases. The series plays on the chemistry between smarmy Shore and loose cannon Denny Crane. Middle-aged Shore is wry and wily, while mid-70s Crane (suffering from early onset Alzheimer's disease )

168-406: 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

252-470: 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

336-456: 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

420-609: A dozen subtle expressions or inflections." Other Crimson critics described his performances in Shakespeare plays as "a tour de force of sheer talent and intelligence" (in The Winter's Tale ) and "a very fine and subtle performance" (in Measure for Measure ). He displayed early on his remarkable range when he undertook with inimitable flair and hilarious effect the hugely solemn role of Erde "the green-faced torso", goddess of

504-404: 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

588-409: 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

672-435: 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

756-485: A passenger revolt . He also had a recurring role on Veronica Mars as Abel Koontz. In total, Clemenson appeared in three episodes of the show: " Like a Virgin ", " Mars vs. Mars ", and " Rat Saw God ". Clemenson also has appeared in a season 6 episode of NCIS , "Dead Reckoning". He also appeared in two season 2 episodes of The Mentalist . He also played Jimmy Masterson on the 3rd episode of Memphis Beat , "Love Me Tender". In 2009, Clemenson joined CSI: Miami as

840-537: 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

924-524: A series regular, having joined the cast of My Own Worst Enemy . The final season consisted of 13 episodes to reach the "100" episode mark, which facilitated successful syndication. There was speculation that Boston Legal might receive an additional episode order, if the show had another strong showing in the Emmy Awards and produced solid ratings in its new fall time slot. The season began airing on September 22, 2008. On June 18 and June 20, 2008, it

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1008-462: A working title of Fleet Street , an allusion to the real street in Boston where the fictitious Crane, Poole & Schmidt had its offices. The working title was later modified to The Practice: Fleet Street , but this title was dropped in favor of Boston Legal . The real building shown as the law office is located at 500 Boylston Street , 1.4 miles away from Fleet Street. The American producers of

1092-561: 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

1176-488: Is a medical hypothesis that just as the fetus goes through a process of neurodevelopment beginning with neurulation and ending with myelination , 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

1260-496: 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

1344-529: 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

1428-491: 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

1512-435: Is complex and focuses on asymptomatic individuals; the latter two stages describe individuals experiencing symptoms. The core clinical criteria for MCI 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

1596-405: Is disrupted in Alzheimer's disease, though it remains unclear whether this 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

1680-526: Is divided into probable and possible AD dementia. In probable AD dementia there is steady impairment of cognition over time and 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

1764-409: Is flamboyant and eccentric. Shore often uses questionable methods to win cases. Crane is obsessed with the reputation of his name, which he frequently repeats. Though political opposites, Shore and Crane are best friends. Episodes more often than not end with the two relaxing and musing together on the firm's balcony (while they smoke cigars and sip scotch whisky ). Prior to the show's premiere, it had

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1848-547: 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

1932-406: 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

2016-453: 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,

2100-561: 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

2184-427: 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

2268-513: 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,

2352-484: 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 a person's condition declines, they often withdraw from family and society . Gradually, bodily functions are lost, ultimately leading to death. Although

2436-522: 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

2520-536: 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

2604-770: The Pittsburgh Post-Gazette on December 7, 2008 that it was ABC's decision to end Boston Legal , and that he "had to fight to bring it back for a short season of 13 episodes". The show was noted for frequently breaking the fourth wall throughout its run. According to Nielsen Media Research , Boston Legal drew the richest viewing audience on television, based on the concentration of high-income viewers in its young adult audience (Adult 18–49 index w/$ 100k+ annual income). Seasonal rankings (based on average total viewers per episode) of Boston Legal on ABC . Note: Each U.S. network television season starts in late September and ends in late May, which coincides with

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2688-428: 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 is commonly unaware of their deficits . Many times, families have difficulties in

2772-468: 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

2856-610: 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

2940-619: 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

3024-550: The 2006 Emmy Award for Outstanding Guest Actor in a Drama Series . He has appeared in a number of highly acclaimed films, including Hannah and Her Sisters , Broadcast News , Apollo 13 and The Big Lebowski , and portrayed Tom Burnett in Paul Greengrass ' United 93 . He starred in American Crime Story: The People vs. O.J. Simpson as prosecutor William Hodgman . Clemenson

3108-623: The Earth, in Peter Sellars 's Loeb Drama Center puppet production of Wagner's Ring cycle (1979). During many summers he would return to Humboldt to star in, and later direct, local community theater plays at Humboldt's Castle Theatre. After graduating from Harvard College in 1980 and the Yale School of Drama in 1984, he moved to Los Angeles. Clemenson began his career in a number of character roles in film and television. He

3192-614: 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

3276-521: 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 the earliest stages of the disease. Further neurological examinations are crucial in

3360-751: 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

3444-533: 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

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3528-437: 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

3612-404: 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

3696-523: 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

3780-539: 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

3864-485: The completion of May sweeps . All times mentioned in this section were in the Eastern and Pacific time zones. Primetime Emmy Awards : Golden Globe Awards : Peabody Awards As a former ABC series, the show is available for streaming on Disney platform Hulu . Alzheimer%27s disease Alzheimer's disease ( AD ) is a neurodegenerative disease that usually starts slowly and progressively worsens, and

3948-478: 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,

4032-591: 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

4116-405: 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 the brain . A probable diagnosis is based on the history of

4200-556: 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

4284-423: 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

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4368-462: 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

4452-413: The following are present: no genetic evidence, decline in both learning and memory, two or more cognitive deficits, and 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

4536-452: 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

4620-508: 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

4704-412: The individual has genetic evidence of AD or if two or more acquired cognitive deficits, and 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

4788-401: 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

4872-399: 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

4956-492: 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

5040-808: The movie And the Band Played On . He had a regular role as Socrates Poole, a lawyer in the Old West, in the Fox series The Adventures of Brisco County, Jr. In 1999, Clemenson appeared in the Buffy the Vampire Slayer episode " Bad Girls " as a grotesquely obese demon named Balthazar. He wore a large padded suit and extensive make-up for the role, and the character's repulsive, villainous nature contradicted many of his earlier roles. Clemenson became well-known for his role as Jerry "Hands" Espenson on

5124-445: 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

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5208-582: 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

5292-457: 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

5376-450: 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,

5460-519: 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

5544-594: 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

5628-843: 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

5712-809: 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

5796-708: The series also hired the British writer and barrister John Mortimer (creator of the UK legal series Rumpole of the Bailey ) as a consultant for Boston Legal . The show's pilot was originally produced with former The Practice stars James Spader and Rhona Mitra , guest stars William Shatner and Lake Bell . It featured an expanded storyline with Larry Miller as Edwin Poole, Mark Valley as Brad Chase and John Michael Higgins as senior partner Jerry Austin. Monica Potter

5880-633: The series during the hiatus, while Julie Bowen was cast as Denise Bauer. Ryan Michelle Bathe and Justin Mentell were later cast as junior associates Sara Holt and Garrett Wells. The second episode of season 3 introduced Craig Bierko as Jeffrey Coho and Constance Zimmer as Claire Simms. In episode 11, guest star Gary Anthony Williams joined the cast, with Craig Bierko leaving in episode 15. On June 4, 2007, TV Guide announced that René Auberjonois , Julie Bowen , Mark Valley and Constance Zimmer would not return for season 4. On June 13, 2007, it

5964-427: 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

6048-462: 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 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

6132-410: The symptoms – including tumors or strokes. Delirium and depression can be common among individuals and are important to rule out. Christian Clemenson Christian Dayton Clemenson (born March 17, 1958) is an American actor. He is well known for his portrayal of Jerry "Hands" Espenson in the television series Boston Legal , for which he was nominated for three Emmy Awards and won

6216-400: The television series Boston Legal . For playing Espenson, he won an Emmy Award for Best Guest Actor in a Drama Series in 2006 and was nominated for the same award in 2007. He remained with the series through to its finale in 2008. Clemenson starred in the film United 93 as Tom Burnett , one of the victims of the 9/11 hijacking of the flight that crashed in rural Pennsylvania after

6300-650: 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

6384-615: Was a law student in the television version of The Paper Chase , Alex Keaton 's English teacher in the television show Family Ties , a security salesman on The Golden Girls , a suspect in season 10, episode 14 of NYPD Blue , a bailiff in the Ivan Reitman movie Legal Eagles , a flight surgeon in the movie Apollo 13 , a cop in The Big Lebowski , a killer in The Fisher King , and Dr. Dale Lawrence in

6468-620: Was announced that actor John Larroquette (former The Practice guest star) would join the cast as a senior partner transferred from the New York offices of Crane, Poole & Schmidt, with actress Tara Summers joining as a young associate. Christian Clemenson (former The Practice guest star), who had guest-starred occasionally as Jerry Espenson (a brilliant but socially inept lawyer), was promoted to main cast. Production also stated that René Auberjonois, Mark Valley, Julie Bowen, and Constance Zimmer may return in guest roles. On July 2, 2007, it

6552-709: Was born and raised in Humboldt, Iowa , the son of drug store owners Ruth Alzora (Dayton) and Ernest Arnold Clemenson. In his early teens, he delivered the Des Moines Register , which had a long tradition of awarding scholarships to top East Coast preparatory schools to a select few " paper boys ." Clemenson, a straight-A junior high school student, won a Register scholarship to Phillips Academy in Andover, Massachusetts. He participated in many theatrical productions at Phillips Academy. In 1973, while Clemenson

6636-400: Was enrolled at Phillips, his father died at age 58. Upon graduation from Phillips in 1976, he entered Harvard College . From his freshman year onward he received important roles in campus stage productions. When Clemenson starred in a Harvard Lampoon sketch comedy show, a Harvard Crimson theater critic described Clemenson as "hugely talented actor who can trigger hysteria with any of

6720-493: 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

6804-432: Was later cast as junior partner Lori Colson and René Auberjonois as senior partner Paul Lewiston , replacing John Michael Higgins. The pilot premiered on ABC on October 3, 2004. On November 30, 2004, it was announced that Candice Bergen would join the cast as senior partner Shirley Schmidt, a character the producers had planned to introduce for several months. Lake Bell left the series mid-season, and René Auberjonois

6888-480: Was promoted to main cast member. Anthony Heald and Betty White also made regular guest appearances, having both appeared as the same characters on The Practice . On April 5, 2005, the series was renewed for a second season, although ABC put the show on hiatus in favor of Grey's Anatomy The success of Grey's Anatomy placed Boston Legal on hold until autumn 2005, when it returned for an extended season of 27 episodes. Both Rhona Mitra and Monica Potter left

6972-527: Was reported that Gary Anthony Williams and Taraji P. Henson would not return for season 5 as Clarence Bell and Whitney Rome, respectively. On July 17, 2008, Boston Legal was nominated for a series-high seven Emmy nominations, including for Best Drama Series for the second consecutive year. Spader, Bergen and Shatner were each nominated for their respective roles. Boston Legal' s two-hour-long series finale aired on Monday, December 8, 2008 at 9:00PM Eastern/8:00PM Central. David E. Kelley stated in an interview with

7056-409: Was reported that both René Auberjonois and Mark Valley would return in recurring roles; It was also announced that Taraji P. Henson would join the cast in season 4, with Saffron Burrows appearing in a recurring role. Burrows later became a full-time cast member. On May 13, 2008, ABC announced that Boston Legal would return for a fifth and final season in the fall. Saffron Burrows did not return as

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