Alzheimer's disease Classification and external resources
Histopathologic image of senile plaques seen in the cerebral cortex in a patient with Alzheimer disease of presenile onset. Histopathology (from the Greek histos (tissue and pathos (suffering refers to the microscopic examination of tissue in order to study the manifestations Silver impregnation.
ICD-10	G30., F00.
ICD-9	331.0, 290.1
OMIM	104300
DiseasesDB	490
MedlinePlus	000760
eMedicine	neuro/13
MeSH	D000544

Alzheimer's disease (AD), also called Alzheimer disease or simply Alzheimer's, is the the most common cause of dementia. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings G00-G99 - Diseases of the Nervous system (G00-G09 Inflammatory diseases of the Central nervous system ( Bacterial meningitis The 2007 version of the ICD is available online at http//wwwwho The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. MedlinePlus, with the MedlinePlus Medical Encyclopedia, is a website network containing Health information from the world's largest medical Library eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books Dementia (from Latin de- "apart away" + Mens ( genitive mentis) "mind" is the progressive decline A Delphi study formed an expert consensus estimate that 24 million people worldwide had dementia in 2006, and projected a doubling every twenty years. The Delphi method is a systematic interactive Forecasting method which relies on a panel of independent experts ^[1] Alzheimer's is a degenerative and terminal disease for which there is no known cure. A degenerative disease is a disease in which the function or structure of the affected tissues or organs will progressively deteriorate over time whether due to normal Terminal illness is a medical term popularized in the 20th century to describe an active and Malignant Disease that cannot be cured or adequately treated In its most common form, it afflicts individuals over 65 years old, although a less prevalent early-onset form also exists. The disease can develop many years before it is eventually diagnosed. In its early stages, memory loss, shown as a difficulty to remember recently learned facts, is the most common symptom, although it is often thought to be caused by aging or stress by the sufferer at first. ^[2] Later symptoms include confusion, anger, mood swings, language breakdown, long-term memory loss, and the general withdrawal of the sufferer as his or her senses decline. Confusion, of a Pathological degree usually refers to loss of orientation (ability to place oneself correctly in the world by time location and personal identity and Anger is an emotional state that may range from minor irritation to intense rage A mood swing is an extreme or rapid change in mood. They are commonly associated with Mood disorders of which the classic example is Bipolar disorder (also Long-term memory ( LTM) is Memory that can last as little as a few days or as long as decades ^[2][3] The sufferer gradually loses minor and major bodily functions leading to death. ^[4] Each individual experiences the symptoms of AD in unique ways. ^[5] The duration of the disease is between 5 and 20 years. ^[6][7]

The symptoms of Alzheimer's disease are generally reported to a physician when memory loss becomes apparent. A physician, medical practitioner or medical doctor who practices Medicine, and is concerned with maintaining or restoring human Health If AD is suspected as the cause, the physician or healthcare specialist will confirm the diagnosis with behavioral assessments and cognitive tests, often followed by a brain scan, if it is available. Cognitive tests are Assessments of the Cognitive capabilities of Humans and Animals Tests administered to Humans include various forms Neuroimaging includes the use of various techniques to either directly or indirectly image the structure, function/ Pharmacology of the Brain ^[8]

The cause and progression of Alzheimer's disease is not well understood. Current research indicates that the disease is associated with plaques and tangles in the brain. Senile plaques (syn neuritic plaques senile druse braindruse are extracellular deposits of Amyloid in the Gray matter of the brain Neurofibrillary tangles were first described by Alois Alzheimer in one of his patients suffering from the disorder now referred to as Alzheimer's disease The brain is the center of the Nervous system in animals All Vertebrates and the majority of Invertebrates have a brain ^[9] No treatment has been found to stop or reverse the disease, and it is not known whether current treatments slow the progression, or simply manage the symptoms. Many preventive measures have been suggested for Alzheimer's disease, but their value is unproven in reducing the course and severity of the disease. Mental stimulation, exercise and a balanced diet are often recommended, both as a possible prevention and as a sensible way of managing the disease. Mental exercise is to perform an intellectual stimulating task such as solving a Puzzle (for examples Crosswords or Suduku) or engaging in a game of A healthy diet is one that is arrived at with the intent of improving or maintaining optimal Health. ^[10]

Due to the incurable and degenerative nature of the disease, management of Alzheimer's patient is essential. The role of the main caregiver is often taken by the spouse or a close relative. See also Caregiver See also Carers rights movement As populations age, caregiving and dementia become more common aspects of life ^[11] Caregivers may themselves suffer from stress, over-work, depression, and being physically hit or struck. Major depressive disorder, also known as major depression, unipolar depression, unipolar disorder, clinical depression, or simply depression ^[12]

Characteristics

The disease course is divided into four stages, with a different pattern of cognitive and functional impairment expressed during each stage.

Predementia

Detailed neuropsychological testing can reveal mild cognitive difficulties up to eight years before a person fulfills the clinical criteria of diagnosis. Neuropsychology is the applied scientific discipline that studies the structure and function of the Brain related to specific psychological processes and overt behaviors Diagnosis is the identification by Process of elimination, of the nature of anything ^[13] These early symptoms can have an effect on daily living activities of patients . Activities of daily living ( ADLs) are "the things we normally do in daily living including any daily activity we perform for self-care (such as feeding ourselves bathing Recent studies show impairments in the most complex activities of AD patients. ^[14] The most noticeable deficit is memory loss , shown as a difficulty to remember recently learned facts and an inability to acquire new information. ^[15][16] In addition, subtle executive function problems or semantic memory impairments can also occur. Semantic memory refers to the Memory of meanings Understandings and other concept-based Knowledge unrelated to specific experiences ^[17][18] Apathy can be observed at this stage, and is the most common and persistent neuropsychiatric symptom throughout the course of the disease. Neuropsychiatry is the branch of Medicine dealing with Mental disorders attributable to diseases of the Nervous system. ^[19][20][21] This stage of the disease has also been termed mild cognitive impairment,^[22] but there is still a debate on whether this term corresponds to a different diagnostic entity by itself or just a first step of the disease. Mild cognitive impairment (MCI also known as incipient dementia, or isolated memory impairment) is a Diagnosis given to individuals who have cognitive ^[23]

Early dementia

In 1994 the former United States president R. Reagan informed the country of his AD diagnosis via a hand-written letter. Ronald Reagan 's Alzheimer's letter was a hand-written letter authored by former United States President Ronald Reagan in November 1994 disclosing the fact he had Writing is usually affected in the first stages of the disease.

In most people with the disease the increasing impairments in learning and memory will lead to diagnosis, while in a small proportion of them language, executive or visuoconstructional difficulties will be more salient. ^[24] Nevertheless, memory problems do not affect all memory subcapacities equally. Older memories of the patient'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) are affected to a much lesser degree than the capacities needed to learn new facts or make new memories. Long-term memory ( LTM) is Memory that can last as little as a few days or as long as decades Episodic memory is the Memory of unique personal experiences ( Events Times Places associated Emotions and other conception-based Semantic memory refers to the Memory of meanings Understandings and other concept-based Knowledge unrelated to specific experiences Implicit memory is a type of memory in which previous experiences aid in the performance of a task without conscious awareness of these previous experiences ^[25][26] Language problems are mainly characterised by a shrinking vocabulary and a decreased word fluency which leads to a general impoverishment of oral and written language. Semantic memory refers to the Memory of meanings Understandings and other concept-based Knowledge unrelated to specific experiences The vocabulary of a person is defined either as the set of all Words that are understood by that person or the set of all words likely to be used by that person when constructing Fluency (also called volubility and loquaciousness) is the property of a Person or of a System that delivers Information quickly and The Alzheimer's patient is usually capable of adequately communicating basic ideas. ^[27][28][29] While performing fine motor tasks such as writing, drawing or dressing, certain visoconstructional difficulties, or apraxia, may be present, which may appear as clumsiness. Fine motor skills can be defined as coordination of small Muscle movements which occur e Apraxia is a Neurological disorder characterized by loss of the ability to execute or carry out learned purposeful movements despite having the desire and the physical ability ^[30] As the disease progresses to the middle stage, patients might still be able to live and perform tasks independently for most of the time, but may need assistance or supervision with the most complicated activities. ^[24]

Moderate dementia

In the early stage, people with Alzheimer's can usually care for themselves. At the moderate stage, progressive deterioration seriously hinders the possibility of independence. ^[24]

Speech difficulties become clearly noticeable: the person makes frequent paraphasias due to difficulties in finding words, and content is poor. Paraphasia is a notable feature of Aphasia (also known as Dysphasia) in which one loses the ability of speaking correctly substitutes one word for another and changes Reading and writing are also progressively forgotten. ^[27][31] As time passes, complex motor sequences become less coordinated, costing the patient most of their daily-living abilities. ^[32] Memory problems worsen, and the person may not recognize close relatives. ^[33] Long-term memory, which was previously left intact, is now also impaired. ^[34] At this stage, behavior changes are the norm. Common neuropsychiatric manifestations in this stage are irritability and labile affect, leading to crying or outbursts of unpremeditated aggression and physical violence, even in patients whose life-long behavior has been peaceful. Neuropsychiatry is the branch of Medicine dealing with Mental disorders attributable to diseases of the Nervous system. Irritability is an excessive response to stimuli. Irritability takes many forms from the Contraction of a Unicellular organism when touched to complex Labile affect or pseudobulbar affect refers to the pathological expression of Laughter, Crying or smiling. In Psychology and other social and Behavioral sciences aggression refers to behavior that is intended to cause harm Approximately 30% of the patients also develop illusionary misidentifications and other delusional symptoms. Delusional misidentification syndrome is an umbrella term for a group of Delusional disorders that occur in the context of mental or Neurological illness A delusion is commonly defined as a fixed False Belief and is used in everyday language to describe a belief that is either false fanciful or derived from Deception ^[19][35] Often urinary incontinence develops. ^[36] Because of the communication deficit along with delusions, patients often resist when caregivers attempt to provide care. ^[37] It is important to prevent escalation of resistiveness to care into combativeness when patient might strike out. All these symptoms create stress for relatives and caretakers, increasing the likelihood of moving the patient from home care to other long-term care facilities. Home care, (commonly referred to as domiciliary care) is Health care or supportive care provided in the patient's Home by Healthcare ^[24][38]

Advanced

In the last stage of Alzheimer's disease the subject with the disease is fully dependent. Language is reduced to simple phrases or even single words before being lost altogether. ^[27] Nevertheless many patients can receive and return emotional signals long after the loss of verbal language. ^[39] Although aggressiveness can still be present, extreme apathy and exhaustion are much more common. ^[24] Patients will ultimately not be able to perform even the most simple tasks independently. Finally, deterioration of muscle and mobility will develop, leading the patient to become bedridden,^[40] and to lose the ability to feed oneself,^[41] if death from some external cause, such as infection due to pressure ulcers or pneumonia, does not occur first. Muscle (from Latin musculus, diminutive of mus "mouse" is contractile tissue of the body and is derived from the Bedsores, more properly known as pressure ulcers or decubitus ulcers, are Lesions caused by many factors such as unrelieved Pressure; friction Pneumonia is an inflammatory illness of the Lung. Frequently it is described as lung Parenchyma / alveolar inflammation and abnormal ^[42][43]

Causes

Three major competing hypotheses exist to explain the cause of the disease. The oldest, on which most currently available drug therapies are based, is known as the cholinergic hypothesis and suggests that AD is due to reduced biosynthesis of the neurotransmitter acetylcholine. A receptor is cholinergic if it uses Acetylcholine as its Neurotransmitter. See Chemical synapse for an introduction to concepts and terminology used in this article The Chemical compound acetylcholine (often abbreviated ACh) is a Neurotransmitter in both the Peripheral nervous system (PNS and Central However, the medications that treat acetylcholine deficiency only affect symptoms of the disease and neither halt nor reverse it. ^[44] The cholinergic hypothesis has not maintained widespread support in the face of this evidence, although cholinergic effects have been proposed to initiate large-scale aggregation,^[45] leading to generalised neuroinflammation. ^[46]

In 1991 the amyloid hypothesis was proposed,^[47] while research after 2000 is also centered on tau proteins. Tau proteins are Microtubule-associated proteins that are abundant in Neurons in the Central nervous system and are less common elsewhere The two positions differ with one stating that the tau protein abnormalities initiate the disease cascade, while the other states that amyloid beta (Aβ) deposits are the causative factor in the disease. ^[48]

The tau hypothesis is supported by the long-standing observation that deposition of amyloid plaques does not correlate well with neuron loss. ^[49] In this model, hyperphosphorylated tau begins to pair with other threads of tau and they become tangled up together inside nerve cell bodies in masses known as neurofibrillary tangles. Neurofibrillary tangles were first described by Alois Alzheimer in one of his patients suffering from the disorder now referred to as Alzheimer's disease ^[50] When this happens, the microtubules disintegrate, collapsing the neuron's transport system. This may result first in malfunctions in communication between neurons and later in the death of the cells. ^[51]

A majority of researchers support the alternative hypothesis that Aβ is the primary causative agent. ^[48] The amyloid hypothesis is compelling because the gene for the amyloid beta precursor (APP) is located on chromosome 21, and patients with trisomy 21 (Down Syndrome) who thus have an extra gene copy almost universally exhibit AD-like disorders by 40 years of age. Chromosome 21 is one of the 23 pairs of Chromosomes in Humans People normally have two copies of this chromosome Down syndrome, Down's syndrome, or trisomy 21 is a Chromosomal disorder caused by the presence of all or part of an extra 21st chromosome. Gene dosage is the number of copies of a Gene present in a cell or nucleus. ^[52][53] It should be noted further that ApoE4, the major genetic risk factor for AD, leads to excess amyloid build-up in the brain before AD symptoms arise. Thus, Aβ deposition precedes clinical AD. ^[54] It is known that some types of inherited AD involve only mutations in the APP gene (although this is not the most common type—others involve genes for "pre-senilin" proteins which process APP and may also have still-unknown functions). ^[55] However, another strong support for the amyloid hypothesis, which looks at Aβ as the common initiating factor for Alzheimer's disease, is that transgenic mice solely expressing a mutant human APP gene develop fibrillar amyloid plaques. This article is about organisms which have been genetically modified ^[56]

Pathophysiology

Main article: Biochemistry of Alzheimer's disease

Neuropathology

MRI images of a normal aged brain (right) and an Alzheimer's patient's brain (left). The biochemistry of Alzheimer's disease (AD one of the most common causes of adult Dementia, is as yet not well understood at the molecular level In the Alzheimer brain, atrophy is clearly seen.

At a macroscopic level, AD is characterised by loss of neurons and synapses in the cerebral cortex and certain subcortical regions. Macroscopic is commonly used to describe physical objects that are measurable and observable by the Naked eye. Neurons (ˈnjuːɹɒn also known as neurones and nerve cells) are responsive cells in the Nervous system that process and transmit information Chemical synapses are specialized junctions through which Neurons signal to each other and to non-neuronal cells such as those in Muscles or Glands The cerebral cortex is a structure within the Brain that plays a key role in Memory, Attention, perceptual Awareness, Thought, This results in gross atrophy of the affected regions, including degeneration in the temporal lobe and parietal lobe, and parts of the frontal cortex and cingulate gyrus. Atrophy is the partial or complete Wasting away of a part of the Body. The temporal lobes are parts of the cerebrum that are involved in speech, Memory, and Hearing. The parietal lobe is a lobe in the Brain. It is positioned above (superior to the Occipital lobe and behind (posterior to the Frontal lobe. The frontal lobe is an area in the Brain of Mammals It is located at the front of each Cerebral hemisphere and positioned anterior to (in front of the Cingulate gyrus (belt ridge in eng is a Gyrus in the medial part of the Brain. ^[46]

Both amyloid plaques and neurofibrillary tangles are clearly visible by microscopy in AD brains. Amyloids are insoluble fibrous Protein aggregates sharing specific structural traits Neurofibrillary tangles were first described by Alois Alzheimer in one of his patients suffering from the disorder now referred to as Alzheimer's disease Microscopy is the technical field of using microscopes to view samples or objects ^[9] Plaques are dense, mostly insoluble deposits of amyloid-beta protein and cellular material outside and around neurons. Solubility is the characteristic Physical property referring to the ability of a given substance the Solute, to dissolve in a Solvent. Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl Tangles are insoluble twisted fibers that build up inside the nerve cell. Though many older people develop some plaques and tangles, the brains of AD patients have them to a much greater extent and in different brain locations. ^[57]

Biochemical characteristics

Alzheimer's disease has been identified as a protein misfolding disease, or proteopathy, due to the accumulation of abnormally folded A-beta and tau proteins in the brains of AD patients. Protein folding is the physical process by which a Polypeptide folds into its characteristic and functional three-dimensional structure. Proteopathy (Proteo- protein -pathy disease proteopathies pl. ^[58] Plaques are made of a small peptide (39 to 43 amino acid residues) called beta-amyloid (also A-beta or Aβ), a protein fragment snipped from a larger protein called amyloid precursor protein (APP). Peptides (from the Greek πεπτίδια, "small digestibles" are short Polymers formed from the linking in a defined order of α- Amino Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl Amyloid precursor protein (APP is an Integral membrane protein APP is a transmembrane protein; which means that it sticks through the neuron's membrane; and is believed to help neurons grow, survive and repair themselves after injury. A transmembrane protein is a Protein that spans the entire Biological membrane. ^[59][60] In AD, something causes APP to be divided by enzymes through a mechanism called proteolysis. Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins Proteolysis is the directed degradation ( digestion) of Proteins by cellular Enzymes called Proteases or by intramolecular digestion ^[61] One of these fragments is beta-amyloid. Beta-amyloid fragments (amyloid fibrils) outside the cell form clumps that deposit outside neurons in dense formations known as senile plaques. Senile plaques (syn neuritic plaques senile druse braindruse are extracellular deposits of Amyloid in the Gray matter of the brain ^[62][9]

AD is also considered a tauopathy due to abnormal aggregation of the tau protein. Tauopathies are a class of Neurodegenerative diseases resulting from the pathological aggregation of Tau protein in so-called neurofibrillary tangles (NFT in the human Tau proteins are Microtubule-associated proteins that are abundant in Neurons in the Central nervous system and are less common elsewhere Healthy neurons have an internal support structure, or cytoskeleton, partly made up of structures called microtubules. cytoskeleton (also CSK is a cellular " Scaffolding " or " Skeleton " contained within the Cytoplasm. Microtubules are one of the components of the Cytoskeleton. They have a diameter of 25 nm and length varying from 200 nanometers to 25 micrometers These microtubules act like tracks, guiding nutrients and molecules from the body of the cell down to the ends of the axon and back. An axon or nerve fiber is a long slender projectionof a nerve cell or Neuron, that conducts electrical impulses away from the neuron's Cell A special kind of protein, tau, makes the microtubules stable through a process named phosphorylation and is therefore called a microtubule-associated protein. Phosphorylation is the addition of a Phosphate (PO4 group to a Protein molecule or a small molecule In Cell biology, microtubule-associated proteins (MAPs are proteins that interact with the Microtubules of the cellular Cytoskeleton. ^[63] In AD, tau is changed chemically, becoming hyperphosphorylated. Hyperphosphorylation occurs when a biochemical with multiple Phosphorylation sites is fully saturated

Disease mechanism

If damage from Aβ is the primary initiating cause of AD, the exact mechanism has not been elucidated. The traditional formulation of the amyloid hypothesis points to the cytotoxicity of mature aggregated amyloid fibrils, which are believed to be the toxic form of the protein responsible for disrupting the cell's calcium ion homeostasis and thus inducing apoptosis. ^[64] It is also known that Aβ selectively builds up in the mitochondria of samples from the brains of humans with AD, and in mitochondria from transgenic mice with APP genes, and in both cases inhibits certain mitochondrial enzyme functions, and a similar decrease in glucose utilization in neurons to the one which is a known characteristic of AD. This process may also lead to the formation of damaging reactive oxygen species, calcium influx, and apoptosis. Mechanisms which involve direct damage from Aβ before it forms fibrils and plaques also address the issue that neuronal damage is not correlated as well with plaques, since in this model it is not the plaques themselves which cause the major damage, but rather the precursor Aβ protein directly, via another mechanism. ^[65]

Various inflammatory processes and inflammatory cytokines may also have a role in the pathology of Alzheimer's disease. However, these are general markers of tissue damage in any disease, and may also be either secondary causes of tissue damage in AD, or else bystander "marker" effects. ^[66]

Genetic

While earlier disease familial onset is mainly explained by three genes, later age of disease onset representing most cases of AD has yet to be explained by a purely genetic model. History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance In the second case the APOE gene is the strongest genetic risk factor discovered but it is far from explaining all occurrences of the disease. A risk factor is a variable associated with an increased risk of Disease or Infection. ^[67]

Only 10% of AD cases occurring before 60 years of age are due to autosomal dominant (familial) mutations, which represents less than 0,01 of all patients. ^[67][68] These mutations have been discovered in three different genes: amyloid precursor protein or APP,^[69] and presenilins 1,^[70] and 2^[71]. Amyloid precursor protein (APP is an Integral membrane protein Presenilins are a family of related multi-pass transmembrane proteins that function as a part of the Gamma-secretase protease complex Most mutations in the APP and presenilin genes increase the production of a small protein called Abeta42, which is the main component of senile plaques in brains of AD patients. Senile plaques (syn neuritic plaques senile druse braindruse are extracellular deposits of Amyloid in the Gray matter of the brain ^[72]

Most cases of Alzheimer's disease do not exhibit familial inheritance. In this case genes may act as risk factors. The best known genetic risk factor is the inheritance of the ε4 allele of the apolipoprotein E (ApoE). An allele (ˈæliːl (UK /əˈliːl/ (US (from the Greek αλληλος allelos, meaning each other) is one member of a pair or series of different forms This gene is regarded as a risk factor for development of up to 50% of late-onset sporadic Alzheimer's. ^[73] Genetic experts agree that there are other risk and protective factor genes that influence the development of late onset Alzheimer's disease. ^[67] Over 400 genes have been tested for association with late-onset sporadic AD. ^[74]

Diagnosis

Dementia is by definition a clinical condition but not an exact diagnosis. Dementia (from Latin de- "apart away" + Mens ( genitive mentis) "mind" is the progressive decline Alzheimer's disease is usually diagnosed clinically from the patient history, collateral history from relatives, and clinical observations, based on the presence of characteristic neurological and neuropsychological features and the absence of alternative conditions. Neuropsychology is the applied scientific discipline that studies the structure and function of the Brain related to specific psychological processes and overt behaviors The term diagnosis of exclusion ( per exclusionem) refers to a medical condition whose presence cannot be established with complete confidence from examination or testing ^[75][76] Advanced medical imaging with CT or MRI, and with SPECT or PET are generally used to help to diagnose the subtype of dementia and exclude other cerebral pathology. Medical imaging refers to the techniques and processes used to create Images of the human body (or parts thereof for clinical purposes ( Medical procedures seeking to Computed tomography (CT is a Medical imaging method employing Tomography. Single photon emission computed tomography (SPECT or less commonly SPET is a Nuclear medicine tomographic imaging technique using Gamma rays. A pet is an Animal kept for companionship and enjoyment or a househeld animal as opposed to Livestock, Laboratory animals Working animals ^[77] Neuropsychological evaluation including memory testing and assessment of intellectual functioning can further characterize the dementia. ^[78] Medical organizations have created diagnostic criteria to ease and standardize the process for practicing physicians. Sometimes the diagnosis can be confirmed or made at postmortem when brain material is available and can be examined histologically and histochemically. ^[79]

Diagnostic criteria

The diagnostic criteria for Alzheimer of the NINCDS-ADRDA (NINCDS and the ADRDA) are among the most used. The NINCDS-ADRDA Alzheimer's Criteria were proposed in 1984 by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease The National Institute of Neurological Disorders and Stroke is a part of the U ^[80] These criteria require that the presence of cognitive impairment and a suspected dementia syndrome be confirmed by neuropsychological testing for a clinical diagnosis of possible or probable AD while they need histopathologic confirmation (microscopic examination of brain tissue) for the definitive diagnosis. Neuropsychological assessment was traditionally carried out to assess the extent of impairment to a particular skill and to attempt to locate an area of the brain which may have been damaged Histopathology (from the Greek histos (tissue and pathos (suffering refers to the microscopic examination of tissue in order to study the manifestations Microscopic is a term used to describe objects smaller than those that can easily be seen by the naked Eye and which require a lens or Microscope to see The human brain controls the Central nervous system (CNS by way of the Cranial nerves and Spinal cord, the Peripheral nervous system (PNS They have shown good reliability and validity. In Statistics, reliability is the consistency of a set of measurements or measuring instrument often used to describe a test. In Psychology, validity has two distinct fields of application ^[81] They specify as well eight cognitive domains that may be impaired in AD (i. e. , memory, language, perceptual skills, attention, constructive abilities, orientation, problem solving and functional abilities). In Psychology, memory is an organism's ability to store retain and subsequently retrieve information A language is a dynamic set of visual auditory or tactile Symbols of Communication and the elements used to manipulate them In Psychology and the Cognitive sciences perception is the process of attaining awareness or understanding of sensory Information. Attention is the Cognitive process of selectively concentrating on one aspect of the environment while ignoring other things Orientation is a function of the Mind involving awareness of three dimensions Time, Place and Person. Problem solving forms part of thinking. Considered the most complex of all intellectual functions problem solving has been defined as higher-order Cognitive Similar to the NINCDS-ADRDA Alzheimer's Criteria are the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria published by the American Psychiatric Association. The Diagnostic and Statistical Manual of Mental Disorders' ( DSM) is published by the American Psychiatric Association The American Psychiatric Association (APA is the main Professional organization of Psychiatrists and trainee psychiatrists in the United States, and the ^[82][83]

Diagnostic tools

Neuropsychological screening tests can help in the diagnosis of AD. In them patients have to copy drawings similar to the one shown in the picture, remember words, read or sum.

Neuropsychological screening tests as the Mini mental state examination (MMSE) are widely used to evaluate the cognitive impairments needed for diagnosis, but more comprehensive batteries are necessary for high reliability by this method, especially in the earliest stages of the disease. Screening, in medicine is a strategy used in a Population to detect a Disease in individuals without signs or Symptoms of that disease The mini-mental state examination ( MMSE) or Folstein test is a brief 30-point questionnaire test that is used to assess Cognition. ^[84][85] Neurological examination in early AD will usually be normal, independent of cognitive impairment; but for many of the other dementing disorders is key for diagnosis. Therefore, neurological examination is crucial in the differential diagnosis of Alzheimer and other diseases. A differential diagnosis (sometimes abbreviated DDx, ddx ^[78] In addition, interviews with family members are also utilised in the assessment of the disease. Caregivers can supply important information on the daily living abilities, as well as on the decrease over time of the patient's mental function. ^[86] This is especially important since a patient with AD is commonly unaware of his or her own deficits (anosognosia). Anosognosia is a condition in which a person who suffers Disability due to Brain injury seems unaware of or denies the existence of his or her handicap ^[87] Many times families also have difficulties in the detection of initial dementia symptoms and in adequately communicating them to a physician. ^[88] Finally, supplemental testing provides extra information on some features of the disease or are used to rule out other diagnoses. Examples are blood tests, which can identify other causes for dementia different than AD,^[78] which rarely may even be reversible;^[89] or psychological tests for depression, as depression can both co-occur with AD or, on the contrary, be at the origin of the patient's cognitive impairment. A blood test is a laboratory analysis performed on a Blood sample that is usually extracted from a Vein in the arm using a needle, or via Psychological testing is a field characterized by the use of samples of behavior in order to infer generalizations about a given individual Major depressive disorder, also known as major depression, unipolar depression, unipolar disorder, clinical depression, or simply depression ^[90][91]

Increasingly, the functional neuroimaging modalities of single photon emission computed tomography (SPECT) and positron emission tomography (PET) are being used to diagnose Alzheimer's, as they have shown similar ability to diagnose Alzheimer's disease as methods involving mental status examination. Functional neuroimaging is the use of Neuroimaging technology to measure an aspect of brain function often with a view to understanding the relationship between activity in Single photon emission computed tomography (SPECT or less commonly SPET is a Nuclear medicine tomographic imaging technique using Gamma rays. Positron emission tomography ( PET) is a Nuclear medicine imaging technique which produces a three-dimensional image or map of functional processes in the The mental status examination (or mental state examination in the UK and Australia abbreviated MSE, is an important part of the clinical assessment process ^[92] Furthermore, the ability of SPECT to differentiate Alzheimer's disease from other possible causes, in a patient already known to be suffering from dementia, appears to be superior to attempts to differentiate the cause of dementia cause by mental testing and history. ^[93] A new technique known as "PiB PET" has been developed for directly and clearly imaging beta-amyloid deposits in vivo using a contrasting tracer that binds selectively to the Abeta deposits. Positron emission tomography ( PET) is a Nuclear medicine imaging technique which produces a three-dimensional image or map of functional processes in the In vivo ( Latin: within the living means that which takes place inside an organism. RadiocontrastIn a medical setting a contrast medium is any Substance that is used to enhance the visibility of structures or fluids within the body A radioactive tracer, also called a radioactive label, is a substance containing a Radioisotope (which is an isotope that has an unstable nucleus and that stabalizes Molecular binding is an attractive interaction between two Molecules which results in a stable association in which the two molecules are in close proximity to each other ^[94][95][96] Another recent objective marker of the disease is the analysis of cerebrospinal fluid for amyloid beta or tau proteins. Cerebrospinal fluid ( CSF) Liquor cerebrospinalis, is a clear Bodily fluid that occupies the Subarachnoid space and the Ventricular system Tau proteins are Microtubule-associated proteins that are abundant in Neurons in the Central nervous system and are less common elsewhere ^[97] Both advances (neuroimaging and cerebrospinal fluid analysis) have led to the proposal of new diagnostic criteria. ^[80][78]

Prevention

Intellectual activities such as playing chess or regular social interaction have been linked to a reduced risk of AD in epidemiological studies, although no causal relationship has been found.

At present contradictory results in global studies, incapacity to prove causal relationships between risk factors and the disease, and possible secondary effects indicate a lack of specific measures to prevent or delay the onset of AD. ^[98] Different epidemiological studies have proposed relationships between certain modifiable factors, such as diet, cardiovascular risk, pharmaceutical products, or intellectual activities among others, and a population's likelihood of developing AD. Only further research, including clinical trials, will reveal whether, in fact, these factors can help to prevent AD. ^[99]

The components of a Mediterranean diet, which include fruit and vegetables, bread, wheat and other cereals, olive oil, fish, and red wine, may all individually or together reduce the risk and course of Alzheimer's disease. The Mediterranean diet is a modern nutritional recommendation inspired by the traditional dietary patterns of some of the countries of the Mediterranean Basin. Bread is a Staple food prepared by Baking a Dough of Flour and Water. Wheat ( Triticum spp is a worldwide cultivated grass from the Levant area of the Middle East. Olive oil is a fruit oil obtained from the olive ( Olea europaea; family Oleaceae along with Lilacs Jasmine and ash trees Fish are aquatic Vertebrate animals that are typically ectothermic (previously Cold-blooded) covered with scales, and equipped with two Wine is an Alcoholic beverage made from the fermentation of Grape juice There is evidence that frequent and moderate consumption of alcohol (beer, wine or distilled spirits) reduces the risk of the disease,^{[100] [101]} but it is still considered premature to make dietary recommendations on this basis. ^[102][103] Vitamins B and C, or folic acid have appeared to be related to a reduced risk of AD,^[104] but other studies indicate that they do not have any significant effect on the onset or course of the disease, but may have important secondary effects in conjunction with other therapies. The B vitamins are eight water-soluble Vitamins that play important roles in cell Metabolism. Vitamin C or L-ascorbate is an Essential nutrient for a large number of higher primate species a small number of other Mammalian Folic acid (also known as Vitamin M and Folacin) and Folate (the Anionic form are forms of the water-soluble Vitamin B9 ^[105] Curcumin in curry has shown some effectiveness in preventing brain damage in mouse models. Curcumin is the principal curcuminoid of the popular Indian curry spice Turmeric, the other two Curcuminoids being desmethoxycurcumin and bis-desmethoxycurcumin Curry is the English description of any of a general variety of spicy dishes best known in Indian, Pakistani, Bangladeshi, Sri Lankan See also Animal testing Rodents are commonly used in animal testing, particularly guinea pigs hamsters gerbils rats and mice ^[106]

Although cardiovascular risk factors, such as hypercholesterolemia, hypertension, diabetes, and smoking, are associated with a higher risk of onset and course of AD,^[107][108] statins, which are cholesterol lowering drugs, have not been effective in preventing or improving the course of the disease. Hypercholesterolemia (literally high blood cholesterol is the presence of high levels of Cholesterol in the blood. Hypertension, also referred to as high blood pressure, HTN or HPN, is a medical condition in which the Blood pressure is chronically elevated Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc The statins (or HMG-CoA reductase inhibitors) form a class of hypolipidemic drugs used to lower Cholesterol levels in people with or at risk of Cardiovascular Cholesterol is a Lipid found in the Cell membranes and transported in the Blood plasma of all Animals It is an essential component of mammalian ^[109][110] However long-term usage of non-steroidal anti-inflammatory drug (NSAIDs), is associated with a reduced likelihood of developing AD in some individuals. Non-steroidal anti-inflammatory drugs, usually abbreviated to NSAID s or NAID s, are drugs with Analgesic, Antipyretic and in higher ^[111]

Other pharmaceutical therapies such as female hormone replacement therapy are no longer thought to prevent dementia,^[112][113] and a 2007 systematic review concluded that there was inconsistent and unconvincing evidence that ginkgo has any positive effect on dementia or cognitive impairment. Hormone replacement therapy may refer to Hormone replacement therapy (menopause Hormone replacement therapy (female-to-male A systematic review is a Literature review focused on a single question which tries to identify appraise select and synthesize all high quality research evidence relevant to Ginkgo ( Ginkgo biloba; in Chinese 銀杏 Pinyin romanization yín xìng) frequently misspelled as "Gingko" and also known ^[114]

Intellectual activities such as playing chess, completing crossword puzzles or regular social interaction, may also delay the onset or reduce the severity of Alzheimer's disease. Chess is a recreational and competitive Game played between two players. A puzzle is a Problem or Enigma that challenges Ingenuity. In a basic puzzle one is intended to piece together objects in a logical way in order to Social interaction is a dynamic changing sequence of Social actions between individuals (or groups who modify their actions and reactions according to the actions by their ^[115][116] Bilingualism is also related to a later onset of Alzheimer. ^[117]

Management

There is no known cure for Alzheimer's disease. Available treatments offer relatively small symptomatic benefit but remain palliative in nature. Palliative care (from Latin palliare to cloak is any form of medical care or treatment that concentrates on reducing the severity of Disease Symptoms Current treatments can be divided into pharmaceutical, psychosocial and caregiving.

Pharmaceutical

3d molecular spacefill of donepezil, an acetylcholinesterase inhibitor used in the treatment of AD symptoms

Molecular structure of memantine, a medication approved for advanced AD symptoms

Four medications, to treat the cognitive manifestations of AD, are currently approved by regulatory agencies, including the U. Donepezil (also used incorrectly as Donezepil marketed under the trade name Aricept ( Eisai) ( Pfizer) is a centrally acting reversible Acetylcholinesterase An acetylcholinesterase inhibitor or anti-cholinesterase is a chemical that inhibits the Cholinesterase enzyme from breaking down Acetylcholine Memantine is the first in a novel class of Alzheimer's disease medications acting on the Glutamatergic system by blocking NMDA glutamate receptors S. Food and Drug Administration (FDA) and the European Medicines Agency (EMEA). The European Medicines Agency ( EMEA) is a European agency for the evaluation of medicinal products. Three are acetylcholinesterase inhibitors and the other is memantine, an NMDA receptor antagonist. An acetylcholinesterase inhibitor or anti-cholinesterase is a chemical that inhibits the Cholinesterase enzyme from breaking down Acetylcholine Memantine is the first in a novel class of Alzheimer's disease medications acting on the Glutamatergic system by blocking NMDA glutamate receptors The NMDA receptor ( NMDAR) is an Ionotropic receptor for Glutamate ( NMDA ( N -methyl D -aspartate is a name of its selective A receptor antagonist is a type of receptor ligand or Drug that does not provoke a biological response itself upon binding to a receptor, but blocks No drug has an indication for delaying or halting the progression of the disease.

Because reduction in the activity of the cholinergic neurons in the disease is well known,^[118] acetylcholinesterase inhibitors are employed to reduce the rate at which acetylcholine (ACh) is broken down and so to increase the concentration of ACh in the brain, thereby combatting the loss of ACh caused by the death of the cholinergin neurons. A receptor is cholinergic if it uses Acetylcholine as its Neurotransmitter. An acetylcholinesterase inhibitor or anti-cholinesterase is a chemical that inhibits the Cholinesterase enzyme from breaking down Acetylcholine The Chemical compound acetylcholine (often abbreviated ACh) is a Neurotransmitter in both the Peripheral nervous system (PNS and Central ^[119] Cholinesterase inhibitors currently approved include donepezil (brand name Aricept),^[120] galantamine (Razadyne),^[121] and rivastigmine (branded as Exelon,^[122] and Exelon Patch^[123]). Donepezil (also used incorrectly as Donezepil marketed under the trade name Aricept ( Eisai) ( Pfizer) is a centrally acting reversible Acetylcholinesterase Galantamine (trade names Razadyne, Razadyne ER, Reminyl, Memeron) is a drug used for the treatment of mild to moderate Alzheimer’s disease Rivastigmine (sold under the trade name Exelon) is a parasympathomimetic or Cholinergic agent that was developed by Novartis for the treatment There is also evidence for the efficacy of these medications in mild to moderate Alzheimer’s disease,^[124] and some evidence for their use in the advanced stage. Only donepezil is approved for treatment of advanced AD dementia. ^[125] The use of these drugs in mild cognitive impairment has not shown any effect in a delay of the onset of AD. Mild cognitive impairment (MCI also known as incipient dementia, or isolated memory impairment) is a Diagnosis given to individuals who have cognitive ^[126] Most common side effects include nausea and vomiting, both of which are linked to cholinergic excess. Side Effect were an influential Disco band that recorded between 1972 and 1995 Nausea ( Latin: Nausea, Greek:, " Sea-sickness " also called wamble) is the sensation of unease and discomfort Vomiting (also called throwing up, emesis) is the forceful expulsion of the contents of one's Stomach through the Mouth and sometimes the These side effects arise in approximately ten to twenty percent of users and are mild to moderate in severity. Less common secondary effects include muscle cramps; decreased heart rate (bradycardia), decreased appetite and weight, and increased gastric acid. Cramps, sometimes called Charley horses are unpleasant often painful sensations caused by contraction or over shortening of Muscles Cramps can be caused by cold Measuring heart rate The Pulse rate (which in most people is identical to the heart rate can be measured at any point on the body where an Artery 's pulsation Bradycardia, as applied to adult medicine is defined as a resting Heart rate of under 60 beats per minute though it is seldom symptomatic until the rate drops below 50 beat/min Gastric acid is one of the main Secretions of the Stomach, together with several Enzymes and Intrinsic factor. ^{[127][128][129][130]}

Glutamate is a useful excitatory neurotransmitter of the nervous system, although excessive amounts in the brain can lead to cell death through a process called excitotoxicity which consists of the overstimulation of glutamate receptors. Glutamic acid (abbreviated as Glu or E) is one of the 20 Alpha Amino acids It is not among the human Essential amino acids Its See Chemical synapse for an introduction to concepts and terminology used in this article The brain is the center of the Nervous system in animals All Vertebrates and the majority of Invertebrates have a brain Excitotoxicity is the pathological process by which nerve cells are damaged and killed by glutamate and similar substances In Biochemistry, a receptor is a Protein molecule embedded in either the Plasma membrane or Cytoplasm of a cell to which a mobile signaling Excitotoxicity occurs not only in Alzheimer's disease, but also in other neurological diseases such as Parkinson's disease and multiple sclerosis. Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the Central nervous system that often impairs the sufferer's Multiple sclerosis (abbreviated MS also known as disseminated sclerosis or encephalomyelitis disseminata) is an autoimmune condition in which the ^[131] Memantine (brand names Akatinol, Axura, Ebixa/Abixa, Memox and Namenda),^[132] is a noncompetitive NMDA receptor antagonist first used as an anti-influenza agent. Memantine is the first in a novel class of Alzheimer's disease medications acting on the Glutamatergic system by blocking NMDA glutamate receptors The NMDA receptor ( NMDAR) is an Ionotropic receptor for Glutamate ( NMDA ( N -methyl D -aspartate is a name of its selective A receptor antagonist is a type of receptor ligand or Drug that does not provoke a biological response itself upon binding to a receptor, but blocks It acts on the glutamatergic system by blocking NMDA glutamate receptors and inhibits their overstimulation by glutamate. The glutamatergic Neurotransmitter system plays a crucial role in memory formation and information processing ^[131] Memantine has been shown to be moderately efficacious in the treatment of moderate to severe Alzheimer’s disease. Its effects in the initial stages are unknown. ^[133] Reported adverse events with memantine are infrequent and mild, including hallucinations, confusion, dizziness, headache and fatigue. A hallucination, in the broadest sense is a Perception in the absence of a stimulus. Confusion, of a Pathological degree usually refers to loss of orientation (ability to place oneself correctly in the world by time location and personal identity and Many different terms are often used to describe what is collectively known as dizziness. A headache ( cephalalgia in medical terminology is a condition of pain in the Head; sometimes Neck or upper back pain may also be interpreted ^[134] Memantine used in combination with donepezil has been shown to be "of statistically significant but clinically marginal effectiveness". ^[135]

Neuroleptic anti-psychotic drugs commonly given to Alzheimer's patients with behavioural problems are modestly useful in reducing aggression and psychosis, but are associated with serious adverse effects, such as cerebrovascular events, movement difficulties or cognitive decline, that do not permit their routine use. Antipsychotics are a group of Psychoactive drugs commonly but not exclusively used to treat Psychosis, which is typified by Schizophrenia. Antipsychotics are a group of Psychoactive drugs commonly but not exclusively used to treat Psychosis, which is typified by Schizophrenia. In Psychology and other social and Behavioral sciences aggression refers to behavior that is intended to cause harm Psychosis (from the Greek ψυχή "psyche" for mind or soul and -οσις "-osis" for abnormal condition with adjective psychotic Cerebrovascular disease is a group of brain dysfunctions related to disease of blood vessels supplying the brain In Human anatomy, the extrapyramidal system is a Neural network located in the brain that is part of the Motor system involved in the coordination ^{[136][137][138]}

Psychosocial intervention

A specifically designed room for sensory integration therapy, or snoezelen; an emotion-oriented psychosocial intervention for people with dementia

Psychosocial interventions are used as an adjunct to pharmaceutical treatment and can be classified within behavior, emotion, cognition or stimulation oriented approaches. The term psychosocial refers to one in Psychological development in and interaction with a Social environment. Research on efficacy is unavailable and rarely specific to the disease, focusing instead on dementia. ^[139]

Behavioral interventions attempt to identify and reduce the antecedents and consequences of problem behaviors. Behavior modification is the use of empirically demonstrated behavior change techniques to improve behavior such as altering an individual's behaviors and reactions to stimuli through This approach has not shown success in the overall functioning of patients,^[140] but can help to reduce some specific problem behaviors, such as incontinence. Urinary incontinence ( UI) is any involuntary leakage of Urine. ^[141] There is still a lack of high quality data on the effectiveness of these techniques in other behavior problems such as wandering. ^[142][143]

Emotion-oriented interventions include reminiscence therapy, validation therapy, supportive psychotherapy, sensory integration or snoezelen, and simulated presence therapy. Reminiscence therapy is a relatively low cost therapy usually used to counsel and support older people and is a useful intervention in work with brain-injured patients Validation therapy was developed by Naomi Feil for older people with cognitive impairments and Dementia. Psychotherapy is an Interpersonal, relational intervention used by trained psychotherapists to aid clients in problems of living Snoezelen or controlled multisensory stimulation is used for people with mental disabilities and involves exposing them to a soothing and stimulating environment Simulated presence therapy is an emotion-oriented non pharmacological intervention for people with Dementia. Supportive psychotherapy has received little or no formal scientific study, but some clinicians find it useful in helping mildly impaired patients adjust to their illness. ^[139] Reminiscence therapy (RT) involves the discussion of past experiences individually or in group, many times with the aid of photographs, household items, music and sound recordings, or other familiar items from the past. Although there are few quality studies on the effectiveness of RT it may be beneficial for cognition and mood. Cognition is a concept used in different ways by different disciplines but is generally accepted to mean the process of awareness or thought A mood is a relatively long lasting affective or emotional state ^[144] Simulated presence therapy (SPT) is based on attachment theories and is normally carried out playing a recording with voices of the closest relatives of the patient. Attachment theory, originating in the work of John Bowlby, is a Psychological, evolutionary and ethological theory that provides a descriptive There is preliminary evidence indicating that SPT may reduce anxiety and challenging behaviors. Anxiety is a physiological and psychological state characterized by Cognitive, Somatic, Emotional and Behavioral components Challenging behavior is defined as "culturally abnormal Behavior (s of such intensity frequency or duration that the physical Safety of the person or others ^[145][146] Finally, validation therapy is based on acceptance of the reality and personal truth of another's experience, while sensory integration is based on exercises aimed to stimulate senses. Senses are the physiological methods of Perception. The senses and their operation classification and theory are overlapping topics studied by a variety of fields There is little evidence to support the usefulness of these therapies. ^[147][148]

The aim of cognition-oriented treatments, which include reality orientation and cognitive retraining is the restoration of cognitive deficits. Rehabilitation of sensory and Cognitive function typically involves methods for retraining Neural pathways or training new neural pathways to regain or improve neurocognitive Cognitive deficit is an inclusive term to describe any characteristic that acts as a barrier to cognitive performance Reality orientation consists in the presentation of information about time, place or person in order to ease the understanding of the person about its surroundings and his place in them. On the other hand cognitive retraining tries to improve impaired capacities by exercitation of mental abilities. Both have shown some efficacy improving cognitive capacities,^[149][150] although in some works these effects were transient and negative effects, such as frustration, have also been reported. ^[139]

Stimulation-oriented treatments include art, music and pet therapies, exercise, and any other kind of recreational activities for patients. Art therapy is a form of Expressive therapy that uses art materials such as paints chalk and markers Music therapy is an interpersonal process in which the therapist uses music and all of its facets&mdashphysical emotional mental social aesthetic and spiritual&mdashto help clients to improve Animal-assisted therapy (AAT is a type of therapy that involves an Animal with specific characteristics becoming a fundamental part of a person's treatment Recreational therapy, also referred to as recreation therapy and therapeutic recreation, contributes to the broad spectrum of Health care through treatment Stimulation has modest support for improving behavior, mood, and, to a lesser extent, function. Nevertheless, as important as these effects are, the main support for the use of stimulation therapies is the improvement in the patient daily life routine they suppose. ^[139]

Caregiving

Further information: Caregiving and dementia

Since there is no cure for Alzheimer's, caregiving is an essential part of the treatment. See also Caregiver See also Carers rights movement As populations age, caregiving and dementia become more common aspects of life Due to the eventual inability for the sufferer to self-care, Alzheimer's has to be carefully care-managed. Home care in the familiar surroundings of home may delay onset of some symptoms and delay or eliminate the need for more professional and costly levels of care. ^[151] Many family members choose to look after their relative,^[12] but two-thirds of nursing home residents have dementias. ^[152]

Modifications to the living environment and lifestyle of the Alzheimer's patient can improve functional performance and ease caretaker burden. Assessment by an occupational therapist is often indicated. An occupational therapist (OT is a health professional who is trained in the practice of Occupational therapy. Adherence to simplified routines and labeling of household items to cue the patient can aid with activities of daily living, while placing safety locks on cabinets, doors, and gates and securing hazardous chemicals can prevent accidents and wandering. Activities of daily living ( ADLs) are "the things we normally do in daily living including any daily activity we perform for self-care (such as feeding ourselves bathing Changes in routine or environment can trigger or exacerbate agitation, whereas well-lit rooms, adequate rest, and avoidance of excess stimulation all help prevent such episodes. ^[153][154] Appropriate social and visual stimulation can improve function by increasing awareness and orientation. For instance, boldly colored tableware aids those with severe AD, helping people overcome a diminished sensitivity to visual contrast to increase food and beverage intake. ^[155]

Clinical research

Main article: Alzheimer's disease clinical research

As of 2008, the safety and efficacy of more than 400 pharmaceutical treatments are being investigated in clinical trials worldwide, and approximately one-fourth of these compounds are in Phase III trials, which is the last step prior to review by regulatory agencies. As of 2008 there were more than 400 Clinical trials underway to understand and treat Alzheimer's disease. In health care clinical trials are conducted to allow safety and Efficacy data to be collected for new drugs or devices In health care clinical trials are conducted to allow safety and Efficacy data to be collected for new drugs or devices ^[156] It is unknown as to whether any of these trials will ultimately prove successful in treating the disease.

A critical area of clinical research is focused on treating the underlying disease pathology. Reduction of amyloid beta levels is a common target of compounds under investigation. Immunotherapy or vaccination for the amyloid protein is one treatment modality under study. Immunotherapy in medicine refers to an array of treatment strategies based upon the concept of modulating the Immune system to achieve a prophylactic and/or Vaccination is the administration of Antigenic material (the Vaccine) to produce immunity to a disease Unlike vaccines which seek to prevent disease, this therapy would be used to treat diagnosed patients, and is based upon the concept of training the immune system to recognize, attack, and reverse deposition of amyloid, thereby altering the course of the disease. ^[157] An example of such a vaccine under investigation is ACC-001. ^[158][159] Similar agents are bapineuzumab, an antibody designed as identical to the naturally-induced anti-amyloid antibody,^[160] and MPC-7869, a selective amyloid beta-42 lowering agent. Bapineuzumab is a Humanized Monoclonal antibody that acts on the Nervous system and has potential therapeutic value for the treatment of Alzheimer's Tarenflurbil, or R -flurbiprofen, is the single Enantiomer of the racemate NSAID Flurbiprofen. ^[161] Other approaches are neuroprotective agents, such as AL-108,^[162] metal-protein interaction attenuation agents, such as PBT2,^[163] or tumor necrosis factor-alpha receptor fusion proteins, such as etanercept. Tumor necrosis factor ( TNF, cachexin or cachectin and formally known as Tumor necrosis factor-alpha) is a Cytokine involved in systemic Etanercept (Enbrel is a Recombinant -DNA drug made by combining two proteins (a fusion protein ^[164] There are also many basic investigations attempting to increase the knowledge on the origin and mechanisms of the disease that may lead to new treatments.

Prognosis

As the disease progresses, the patient will advance from mild cognitive impairment, when the suspected underlying pathology may or may not yet have been diagnosed, to mild and advanced stages of dementia, finally reaching a severe stage of dementia. ^[24] Individual variations in the presentation and development of the symptoms can make a patient's disease difficult to classify into one specific stage. Once Alzheimer's has been diagnosed, the average life expectancy is approximately seven years, while less than three percent of the patients live more than fourteen years. Life expectancy is the average number of years of life remaining at a given age ^{[165][166][167][6]}

Epidemiology

Alzheimer's disease is the most frequent type of dementia in the elderly and affects almost half of all patients with dementia. Correspondingly, advancing age is the primary risk factor for the disease. Among people aged 65, two to three percent show signs of the disease, while twenty-five to fifty percent of people aged 85 have symptoms of Alzheimer's and an even greater proportion have some of the pathological hallmarks of the disease without the characteristic symptoms. Every five years after the age of 65, the probability of having the disease doubles. ^[168] People over the age of 85 form the fastest growing segment of the Alzheimer's disease population in the US, although current estimates suggest the 75–84 population has about the same number of patients as the over 85 population. ^[169]

The World Health Organization estimates that globally the total disability adjusted life years (DALY) for AD and other dementias exceeded eleven million in 2005, with a projected 3. Disability-adjusted life years (DALY is a measure for the overall Disease burden. 4% annual increase. ^[170] A study in Denmark found that women aged 65 are at significantly higher risk (22 percent) of developing AD by age 95 than their male counterparts (nine percent), while vascular dementias were nearly equal. Multi-infarct dementia, also known as vascular dementia, is the second most common form of Dementia after Alzheimer disease (AD in older adults ^[171]

Some studies have shown a relationship between risk of developing AD and lifetime magnetic field exposure, although the mechanism is unknown. ^[172][173] Other research does not confirm this link. ^[174] The role of metals in the disease is also controversial. The M acro E xpansion T emplate A ttribute L anguage complements TAL, providing macros which allow the reuse of code across ^[175]

History

Auguste D, first described patient with AD

Although the concept of dementia goes as far back as the ancient Greek and Roman philosophers and physicians,^[176] it was in 1901 when Alöis Alzheimer, a German psychiatrist, identified the first case of what became known as Alzheimer's disease in a fifty-year-old woman he called Auguste D. Auguste D was born in May 1850 in an unknown German-speaking part of Europe. Dementia (from Latin de- "apart away" + Mens ( genitive mentis) "mind" is the progressive decline Classical antiquity (also the classical era or classical period) is a broad term for a long period of cultural History centered on the Mediterranean Philosophy is the study of general problems concerning matters such as existence knowledge truth beauty justice validity mind and language A physician, medical practitioner or medical doctor who practices Medicine, and is concerned with maintaining or restoring human Health Aloysius "Alois" Alzheimer (14 June 1864 - 19 December 1915 was a German Psychiatrist and Neuropathologist and a colleague of Emil Kraepelin Psychiatry is a medical specialty which exists to study, prevent, and treat Mental disorders in Humans Psychiatric Auguste D was born in May 1850 in an unknown German-speaking part of Europe. Alöis Alzheimer followed her until she died in 1906, when he first reported the case publicly. ^[177] In the following five years, eleven similar cases were reported in the medical literature, some of them already using the term Alzheimer's disease. Medical literature refers to articles in journals and texts in books devoted to the field of Medicine. ^[176] The official consideration of the disease as a distinctive entity is attributed to Emil Kraepelin, who included Alzheimer’s disease or presenile dementia as a subtype of senile dementia in the eighth edition of his Textbook of Psychiatry, published in 1910. Emil Kraepelin ( February 15, 1856 – October 7, 1926) was a German Psychiatrist. Dementia (from Latin de- "apart away" + Mens ( genitive mentis) "mind" is the progressive decline ^[178]

For most of the twentieth century, the diagnosis of Alzheimer's disease was reserved for individuals between the ages of 45 and 65 who developed symptoms of dementia. The terminology changed after 1977 when a conference concluded that the clinical and pathological manifestations of presenile and senile dementia were almost identical, although the authors also added that this did not rule out the possibility of different etiologies. Etiology (alternatively aetiology, aitiology) is the study of causation. This eventually led to the use of Alzheimer's disease independently of onset age of the disease. ^[179][180] The term senile dementia of the Alzheimer type (SDAT) was used for a time to describe the condition in those over 65, with classical Alzheimer's disease being used for those younger. Eventually, the term Alzheimer's disease was formally adopted in medical nomenclature to describe individuals of all ages with a characteristic common symptom pattern, disease course, and neuropathology. Neuropathology is the study of Disease of nervous system tissue usually in the form of either small surgical biopsies or whole autopsy brains ^[181]

Society and culture

Social costs

Because the median age of the industrialised world's population is gradually increasing, AD is a public health challenge. The solvency of governmental social safety nets will be impacted by the increased aged population which may develop Alzheimer's in the same proportions as earlier generations. ^[182]

Caregiving burden

Further information: Caregiving and dementia

The role of family caregivers has become more prominent in both reducing the social cost of care and improving the quality of life of the patient. See also Caregiver See also Carers rights movement As populations age, caregiving and dementia become more common aspects of life See also Carers rights movement, Caregiving and dementia Carer (UK NZ Australian usage and caregiver (US Canadian usage are words normally Home-based care also can have economic, emotional, and psychological costs to the patient's family. ---- Elderly care or simply eldercare is the fulfillment of the special needs and requirements that are unique to senior citizens Although family members in particular often express the desire to care for the sufferer to the end,^[11] Alzheimer's disease is known for effecting a high burden on caregivers. ^[12]

Alzheimer's disease can incur a variety of stresses on the caregivers: typical complaints are stress, depression, and an inability to cope. Reasons for these complaints can include: high-demands on the caregiver's concentration, as Alzheimer's sufferers have an ever-decreasing regard for their own safety (and can wander when unattended, for example); the lack of gratitude received when the sufferer is unaware of the help being given; and the lack of satisfaction when the sufferer's condition does not abate. Alzheimer's sufferers can be verbally and physically aggressive, and can stubbornly refuse to be helped. Aggression in particular can lead to a temptation to retaliate, which can put both the sufferer and carer at risk. It is additionally stressful for caregivers who are friends and family to witness a sufferer lose his or her identity, and eventually be unable to recognise them. ^[12]

Family caregivers often give up time from work and forego pay to spend 47 hours per week on average with the person with AD. From a 2006 survey of US patients with long term care insurance, direct and indirect costs of caring for an Alzheimer's patient average $77,500 per year. Long-term care insurance ( LTC or LTCI) an Insurance product sold in the United States and United Kingdom, helps provide for ^[183]

Notable cases

Further information: Alzheimer's in the media

As a result of the prevalence of the disease, many notable people have contracted it. This article provides a list of media documents portraying Alzheimer's disease as a critical feature of the main plot Away From Her is Well-known examples are former United States President Ronald Reagan and Irish writer Iris Murdoch, both of whom have scientific articles on how their cognitive capacities deteriorated with the disease. The President of the United States is the Head of state and Head of government of the United States and is the highest political official in United States by Dame Jean Iris Murdoch DBE ( 15 July 1919 &ndash 8 February 1999) was a Dublin -born writer and philosopher ^[184][185] Other cases include the retired footballer Ferenc Puskas,^[186] the former British Prime Minister Harold Wilson,^[187] the actress Rita Hayworth,^[188] the actor Charlton Heston,^[189] and the novelist Terry Pratchett. A footballer is a person who plays in various games known as " Football " &ndash especially Association football, although the term is also used to refer Ferenc Purczeld Biró ( 2 April 1927 &ndash 17 November 2006) or "Ferenc Puskás", was a legendary Hungarian This article is about the government position For other uses see Prime Minister (disambiguation. James Harold Wilson Baron Wilson of Rievaulx, KG, OBE, FRS, PC (11 March 1916 &ndash 24 May 1995 was one of the most prominent British politicians Rita Hayworth (October 17 1918 &ndash May 14 1987 born Margarita Carmen Cansino was a Spanish-American actress who rose to stardom in the 1940s as the era's leading Sex symbol Charlton Heston (born John Charles Carter; October 4 1923 &ndash April 5 2008) was an American Actor of Terence David John Pratchett, OBE (born 28 April 1948 is an English fantasy, Science fiction, and children's author. ^[190]

Alzheimers has also been portrayed in films such as Iris (2001),^[191] (based on John Bayley's memoir of his wife Iris Murdoch),^[192] The Notebook (2004),^[193] (based on Nicholas Sparks' 1996 novel of the same name)^[194] Thanmathra (2005),^[195] Memories of tomorrow (Ashita no Kioku) (2006),^[196] (based on Hiroshi Ogiwara's novel of the same name),^[197] and Away From Her (2006), (based on Alice Munro's short story The Bear Came Over the Mountain),^[198] in documentaries, such as Malcolm and Barbara: A Love Story (1999) and Malcolm and Barbara: Love’s Farewell (2007) both featuring Malcolm Pointon,^[199] and in television series. Iris is a 2001 Film that tells the story of Irish novelist Iris Murdoch and her relationship with John Bayley. The Notebook is a 1996 American Romantic novel by Nicholas Sparks that was later adapted into a popular Romance film Thanmathra ( Molecule) ( 2005) is a Malayalam film directed by Blessy which portrays the effects of Alzheimer's disease on Away from Her is a English- Canadian film directed by Sarah Polley which debuted at the 2006 Toronto International Film Festival Malcolm Pointon (b Unknown - d February 2007 was a Pianist and lecturer from Thriplow, England, and the subject the film Malcolm and Barbara - In The Cider House Rules the affliction of a character with Alzheimer's is mistaken as Alcoholism. The Cider House Rules is a 1985 novel by John Irving. It has been adapted into a film of the same name and a stage play by Peter Parnell. Alcoholism is a term with multiple and sometimes conflicting definitions

References

Further reading

• Cummings JL, Frank JC, Cherry D, Kohatsu ND, Kemp B, Hewett L, Mittman B (2002). "Guidelines for managing Alzheimer's disease: Part I. Assessment". American Family Physician 65 (11): 2263–2272. PMID 12074525.  
• Cummings JL, Frank JC, Cherry D, Kohatsu ND, Kemp B, Hewett L, Mittman B (2002). "Guidelines for managing Alzheimer's disease: Part II. Treatment". American Family Physician 65 (12): 2525–2534. PMID 12086242.  
• Genes, lifestyles, and crossword puzzles: Can Alzheimer's disease be prevented (PDF). US Department of Health and Human Services, National Institute of Aging. Retrieved on 2008-02-29. 2008 ( MMVIII) is the current year in accordance with the Gregorian calendar, a Leap year that started on Tuesday of the Common Leap years Although the modern calendar counts a year as 365 days a complete revolution around the sun takes approximately 365 days and 6 hours
• Russell D, Barston S, White M (2007-12-19). Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 324 - Licinius abdicates his position as Roman Emperor. Alzheimer’s Behavior Management: Learn to manage common behavior problems. helpguide. org. Retrieved on 2008-02-29. 2008 ( MMVIII) is the current year in accordance with the Gregorian calendar, a Leap year that started on Tuesday of the Common Leap years Although the modern calendar counts a year as 365 days a complete revolution around the sun takes approximately 365 days and 6 hours