Alzheimer’S Disease

Alzheimer’s disease

Alzheimer’s disease causes progressive cognitive deterioration and is characterized by beta-amyloid deposits and neurofibrillary tangles in the cortex and in the subcortical gray matter.

Alzheimer’s disease is a neuro cognitive disorder is the most common dementia cause, it makes in the elderly 60 to 80% of the dementias of. In the US, an estimated 13% of ? 65 years and ? 45% of 85 year olds suffer from Alzheimer’s disease. (Editor’s note: According to the Alzheimer Europe (Luxembourg) determined current prevalence rates, suffering in Europe in the age group of 65- to 69-year-olds 1.6% for 80- to 84-year-olds 15.7% and among the over 90-year-olds 41% of Alzheimer’s disease.) The disease occurs in women twice as often as in men, partly because women have a longer life expectancy. In industrialized countries, an increasing prevalence to the extent expected, in which the proportion of older people increases.

Alzheimer’s disease causes progressive cognitive deterioration and is characterized by beta-amyloid deposits and neurofibrillary tangles in the cortex and in the subcortical gray matter. Alzheimer’s disease is a neuro cognitive disorder is the most common dementia cause, it makes in the elderly 60 to 80% of the dementias of. In the US, an estimated 13% of ? 65 years and ? 45% of 85 year olds suffer from Alzheimer’s disease. (Editor’s note: According to the Alzheimer Europe (Luxembourg) determined current prevalence rates, suffering in Europe in the age group of 65- to 69-year-olds 1.6% for 80- to 84-year-olds 15.7% and among the over 90-year-olds 41% of Alzheimer’s disease.) The disease occurs in women twice as often as in men, partly because women have a longer life expectancy. In industrialized countries, an increasing prevalence to the extent expected, in which the proportion of older people increases. Etiology Most cases are sporadic, late-onset (? 65 years) and of unknown etiology. to develop the disease, the risk is best predicted based on age. However, 5-15% of cases have a family history; half of these cases show an early onset (<65 years) and are associated with specific mutations in general. At least 5 different loci, which are located on chromosomes 1, 12, 14, 19 and 21, influence the onset and progression of Alzheimer's dementia. Mutations in genes for the amyloid precursor protein, presenilin I and presenilin II for can cause autosomal dominant forms of Alzheimer's disease, which typically have a presenile onset. In affected patients, the processing of the amyloid precursor protein is altered, which leads to the deposition and fibrillar aggregation of beta amyloid. Beta amyloid is the main component of senile plaques; these consist entirely of degenerate axonal or dendritic projections, astrocytes and glial cells by an amyloid core. Beta-amyloid may also alter kinase and phosphatase activities in a way that will eventually lead to hyperphosphorylation of Tauon and the formation of neurofibrillary tangles. Other genetic determinants affecting the apolipoprotein (Apo) E alleles (?). Apo-E proteins influence the beta-amyloid deposition, the cytoskeletal integrity and the efficiency of neuronal repair mechanisms. In institutions of two ?4 alleles, the risk of Alzheimer's disease is significantly increased in carriers of the ?2 allele may be reduced. For carriers of two ?4 alleles, the risk to develop Alzheimer's disease at the age of 75 years, about 10 to 30 times higher than in people without the allele. Changes in the gene SORL1 may also be involved; they are common in patients with late-onset Alzheimer's disease. These changes may cause the malfunction of the gene, possibly leading to an increased production of beta-amyloid. The relationship between other factors (eg. As low hormone levels, exposure to metals), and Alzheimer's dementia is currently being explored, but no causal references were backed up. Pathophysiology are the 2 pathological hallmarks of Alzheimer's disease The extracellular beta-amyloid deposits (in senile plaques), the intracellular neurofibrillary tangles (paired helical filaments) The beta-amyloid deposits and neurofibrillary tangles lead to the loss of synapses and neurons to performs a coarse atrophy of the affected regions of the brain, which typically begins at the mesial temporal lobe. It has not fully understood by which beta-amyloid peptide and neurofibrillary tangles cause such damage the mechanism. There are several theories. The amyloid hypothesis postulated that progressive accumulation of beta-amyloid in the brain is a complex cascade of events that ends in neuronal cell death, loss of neuronal synapses and neurotransmitters deficits progressive triggers; All these effects contribute to the clinical symptoms of dementia. Prion mechanisms have been identified in Alzheimer's disease. In prion diseases, is a normal brain protein the cell surface, called prion protein misfolded into a pathogenic form, called prion. The prion then causes other prion proteins fold similarly flawed, resulting in a significant increase in abnormal proteins and thus to brain damage. In Alzheimer's disease is believed that beta-amyloid have prion-like, self-replicating properties in cerebral amyloid deposits and tau in neurofibrillary tangles. Symptoms and complaints The patients have symptoms and signs of dementia. The most common first manifestation is loss of short term memory (. Eg face repetitive questions often misplace items or forget appointments) Other cognitive deficits often affect several functions, including the following: impaired reasoning, difficulty in dealing with complex tasks and bad (for example, not being able to manage his bank account to make bad financial decisions) judgment speech disorders (eg. as difficult to remember frequently used words, errors in speaking and / or writing) visuospatial dysfunction (eg to recognize. B. inability faces or common objects) The disease progresses gradually, but may stagnate at a certain level for a certain time. Behavioral disorders (eg. As wandering, agitation, crying, persecutory delusions) are common. Diagnosis As with other dementias Formal survey of mental status history and physical examination laboratory tests Neuroimaging A diagnosis of Alzheimer's disease is generally similar to other forms of dementia (Dementia: Diagnosis). The investigation includes a thorough medical history and a neurological examination standard. With 85% accuracy on the basis of clinical criteria, the diagnosis may be made and an Alzheimer's disease be distinguished from other forms of dementia such as vascular dementia and dementia with Lewy bodies. The traditional diagnostic criteria for Alzheimer's disease all the following include. Clinically properly identified and a formal review of mental status dementia documented deficits in ? 2 areas of cognition Gradual onset (eg for months or years, rather than days or weeks) and progressive deterioration of memory and other cognitive functions no disturbance of consciousness beginning after age 40, most often after the age of 65. No systemic diseases (eg., tumor, stroke) or brain disorders, the progressive deficits could explain in memory and cognition, but not close deviations from these criteria, the diagnosis of Alzheimer's disease in particular because patients may also have a mixed dementia. The latest guidelines from the National Institute on Aging-Alzheimer's Association also include biomarkers in the pathophysiology of Alzheimer's disease model: Low beta amyloid levels in cerebrospinal fluid using a radiotracer, which specifically binds to beta amyloid plaques (eg Pittsburgh Compund B [. PiB] Florbetapir), by means of PET proven ?-amyloid deposits in the brain Other biomarkers show a downstream neuronal degeneration of injury: Increased concentration of tau protein in cerebrospinal fluid Reduced cerebral metabolism in the temporoparietal cortex, determined by FDG-PET, d. H. PET with fluorine-18 (18F) -labeled deoxyglucose (fluorodeoxyglucose or FDG) Local atrophy in the medial basal and lateral temporal lobe and the medial parietal cortex, determined by MRI These results increase the likelihood that the dementia resulting from Alzheimer's disease. However, the guidelines give no recommendation for the routine use of these biomarkers for diagnosis, since both standardization and availability are currently limited. They also do not recommend routine testing for the Apo-?4 allele. (Editor's note: In Germany, the recommendations of the guidelines of the additional diagnostics are as follows: The liquorbasierte neurochemical dementia diagnostics supported under the initial diagnosis to differentiate between primary neurodegenerative dementias and other causes of dementia syndromes, the combined determination of the parameters beta amyloid-1. 42 and total tau and beta-amyloid 1-42 and phospho-Tau is superior to the determination of only a single parameter and is recommended. the differential diagnostic selectivity of these markers within the group of neurodegenerative diseases and in contrast to vascular dementia is not sufficient. the results of the liquorbasierten neurochemical dementia diagnosis should be judged on the basis of the findings of routine CSF and all other available diagnostic information. FDG-PET and SPECT HMPAO can under uncertainty in the Differenzia contribute ldiagnostik of dementia [Alzheimer's disease, vascular dementia, frontotemporal dementia] for clarification. A rule of a use in the diagnosis is not recommended.) Differential Diagnosis The differentiation of Alzheimer's dementia from other dementias is difficult. Assessment aids (. Eg Hachinski ischemia score, see Table: Modified Hachinski ischemia score) can help to differentiate vascular from Alzheimer's dementia. Fluctuations in cognition, Parkinson's symptoms, structured visual hallucinations and a relatively well-preserved short-term memory rather suggest a dementia with Lewy bodies than for Alzheimer's disease (see table: differences between Alzheimer's disease and dementia with Lewy bodies). Patients with Alzheimer's disease are often better maintained and dapper than patients with other dementias. relatively obtain modified Hachinski ischemia score feature points * Sudden onset of symptoms 2 Gradual deterioration (eg. as decrease stability decline) 1 2 Fluctuating course Nocturnal confusion 1 Personality 1 Depression 1 Somatic complaints (eg. B. limb pain, chest pain) 1 1 emotional lability history or presence of hypertension 1 stroke in the Anamnes 2 detecting a concurrent arteriosclerosis (z. B. PAD, myocardial infarction) 1 focal neurological symptoms (z. B. hemiparesis, homonymous hemianopia, aphasia ) 2 Focal neurological signs (eg. B. sided weakness, sensory disturbances, asymmetric reflexes, Babinski sign) 2 * Determination of Total score: <4: Indicates a primary dementia (eg Alzheimer's disease).. 4-7: undetermined. > 7: Suspected. vascular dementia. PAOD = peripheral arterial disease differences between Alzheimer’s disease and dementia with Lewy bodies characteristic of Alzheimer’s disease dementia with Lewy body pathology senile plaques, neurofibrillary tangles and beta amyloid deposits in cerebral cortex and subcortical gray matter Lewy bodies in cortical neurons epidemiology Subject twice as vi ele women and men Subject twice as many men as women inheritance Family in 5-15% of cases rare familial Daily fluctuations Some Prominent short-term memory loss affected Rather deficits in alertness and attention than the memory acquisition Parkinson’s symptoms Very rare in the early stages of the disease Less s, occur in the late stages of the disease Normal transition Prominent, at an early stage of the disease obviously Axial rigidity and unstable transition Autonomous dysfunction Rare Widespread hallucinations occur in about 20% of patients, usually at moderately advanced disease onset at about 80% of patients , usually early in the disease most frequently visually Adverse effects of antipsychotics Spread Possible worsening of dementia symptoms Verbeitet Acute worsening of extrapyramidal symptoms that can be severe or life-threatening prognosis Although the rate of disease progression may be different, the cognitive degradation is inevitable. The average survival time from diagnosis is 7 years, but this information is discussed. The average survival time of immobile patients is approximately 6 months. Treatment generally similar to other forms of dementia may cholinesterase inhibitors and memantine safety and supportive measures are the same as with all dementias. For example, the environment should be bright, friendly and familiar, and it should be designed so that an orientation is reinforced (eg. As placement of large clocks and calendars in the room). Measures to ensure the safety of the patient (eg., Signal monitoring systems for patients who walk) should be initiated. Drugs improve cognitive function and memory in a subset of patients to some extent for the treatment of Alzheimer’s dementia cholinesterase inhibitor. There are four substances available; generally donepezil, rivastigmine and galantamine are equally effective, tacrine but rarely used because of its hepatotoxicity. (Editor’s note: In Germany tacrine is not approved for treatment of Alzheimer’s disease!) Donepezil is the drug of choice because it is given only once a day and well tolerated. (Editor’s note: German Guidelines text: The acetylcholinesterase inhibitors donepezil, galantamine and rivastigmine are approved for the treatment of mild to moderately severe Alzheimer’s dementia and in use.) The recommended dose is 5 mg once daily for 4-6 weeks is then increased to 10 mg / day. Donepezil 23 mg as a single daily dose may be more effective than the traditional 10-mg daily dose of moderate to severe Alzheimer’s disease. (Editor’s note: German dosage recommendations: The effect of acetylcholinesterase inhibitors is dose-dependent, depending on the compatibility of the titration should be carried out to the approved maximum dose (10 mg / day donepezil, 12 mg / day rivastigmine [as a tablet], 9.5. mg rivastigmine [as paving application], 24 mg / day galantamine). All substances must be slowly metered to improve compatibility.) treatment should be continued when a functional improvement after a few months is visible, otherwise they should be stopped. Most common are gastrointestinal side effects (eg. As nausea, diarrhea). Dizziness and cardiac arrhythmias are rare. Adverse effects can be minimized by a slower increase in dose (see table: drugs for Alzheimer’s disease). Memantine, a N-methyl-d-aspartate receptor antagonist appears to improve the performance and functional capacity of patients with moderate to severe Alzheimer’s disease. The dose is 5 mg p.o. once a day and is about 4 weeks to 10 mg p.o. 2 times increased daily. In patients with renal insufficiency, the dose should be reduced or the drug can be avoided. Memantine may be used along with a cholinesterase inhibitor. The efficacy of high-dose vitamin E (1000 IU po 1 or 2 times a day), selegiline, NSAIDs, Ginkgo biloba extracts, and statins is unclear. (Editor’s Note: German guidelines for Neurology: There is no convincing evidence of efficacy ginkgohaltiger preparations They are therefore not recommended The same is true for vitamin E…) Estrogen therapy does not make sense for the prevention or the treatment and can be harmful. Drugs for Alzheimer’s disease Name Initial dose maximum dose Comments donepezil 5 mg 1 times daily 23 mg once a day (with moderate to severe Alzheimer’s dementia). (Editor’s note:. S comment above) General well tolerated but may cause nausea or diarrhea cause galantamine (Editor’s Note: According to Red List in Germany there galantamine nutrals release preparation [8, 16, 24 mg] or as a solution [4 mg / ml]) 4 mg 2 times daily (solution) a sustained-release 8 mg once daily in the morning 12 mg two times daily (solution) Retardkapseln: 24 mg once daily in the morning Influenced behavioral problems may be better than other drugs Modulates the nicotine receptors seems the release to stimulate acetylcholine and increases its effect memantine 5 mg 2 times daily 10 mg 2 times a day used in patients with moderate to severe Alzheimer’s disease. (Editor’s note:. S comment above) rivastigmine solution or capsule: 1.5 mg 2 times daily TTS: 4.6 mg / 24 h or capsule solution: 6 mg 2 times daily TTS: 13.3 mg / 24 h Available Preliminary as a solution and TTS prevention evidence through observation suggests that the risk for Alzheimer’s disease like this can be reduced: Until the ripe old age continuation of challenging mental activities (such as learning new skills, solving. Sporting crossword) type control Hypert onie lower cholesterol diet rich in omega-3 fatty acids and with few saturated fats Moderate alcohol consumption However, there is no convincing evidence that people who take no alcohol at all should begin to drink, to prevent Alzheimer’s disease. Conclusion Although genetic factors may be involved, most cases of Alzheimer’s disease are sporadic, where the risk can best be predicted based on the patient’s age. The differentiation of Alzheimer’s disease from other causes of dementia (. Eg vascular dementia, dementia with Lewy bodies) can be difficult; often it is done best with clinical criteria that provide a 85% accuracy for diagnosis. Alzheimer’s dementia is similar to be treated like other dementias. More information Alzheimer’s Association: New diagnostic criteria and guidelines for Alzheimer’s disease Alzheimer’s Association: The diagnosis of dementia due to Alzheimer’s disease

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