Monday, November 11, 2019
Etiology and Pathogenesis of Alzheimerââ¬â¢s disease
Alzheimerââ¬â¢s disease is a degenerative brain disorder and is the main cause of dementia. The major clinical manifestations of Alzheimerââ¬â¢s disease include gradual loss of memory and language. Other major symptoms and signs of this disease are psychiatric and behavioral abnormalities and disabilities in the routine or daily living activities.The etiology and Pathogenesis of Alzheimerââ¬â¢s disease include various factors. Biological Factors Even though the etiology and pathogenesis of Alzheimerââ¬â¢s disease is still not known fully, it is discovered to involve a complex mix of genetic as well as environmental factors.Among genetic and environmental factors, genetic factor is proved to be playing a major role in the etiology and pathogenesis of Alzheimerââ¬â¢s disease. The most important cause of Alzheimerââ¬â¢s disease is found to be the mutations in chromosomes 21, 14 and 1 which are spread or moved in a typical autosomal dominant mode. These mutations make p rotein overproduction in neuritic plaques, B amyloid. Even though the beginning of the familial form is often early, the nature and route of the disorder is found to be influenced by few environmental factors.But it is found out that familial form is responsible for only a negligible proportion of cases of Alzheimerââ¬â¢s disease (even less than five percent) (Cummings et al. , 1998b). Nearly fifty percent of the people who are having ancestors with Alzheimerââ¬â¢s disease are found to be getting this disorder once they enter their 80s and 90s (Mohs et al. , 1987). Few genotypes (the model of genetic inheritance in a personââ¬â¢s body) are found to give risk for the late-onset Alzheimerââ¬â¢s disease (which is very common).Taking an example, the ApoE-e4 allele on chromosome 19, that encourages the deposition of B amyloid, is proved to increase the risk for developing Alzheimerââ¬â¢s disease (Corder et al. , 1993). All other genes that are doubted to be responsible for the development of Alzheimerââ¬â¢s disorder are being studied (Kang et al. , 1997). Apart from this particular reason, there are various other biological risk factors that contribute to the development of Alzheimerââ¬â¢s disorder Cummings et al. , 1998b).Cognitive capabilities and aging are among the biological factors. The manner in which these traits contribute to the increased risk is not still proved, however, it is proved in the medical field that the numerous neurobiologic changes that are associated with the normal aging of the brain of a person also contribute to the major risk factors of Alzheimerââ¬â¢s disorder. As people get into the later part of their life, this age related neurobiologic changes make then more liable for Alzheimerââ¬â¢s disorder.These neurobiologic changes include neuron and synaptic loss, lessened dendritic span, reduced size and density of neurons present in the nucleus basalis of Meynert, and poor cortical acetylcholine levels (Cummings et al. , 1998b). Based on these factors and the frequency and occurrence curve of this disorder, medical researchers have come to the conclusion that people are very much liable to Alzheimerââ¬â¢s disorder if their life span is extended (beyond the normal age) beyond eighties and nineties (up to 100 and 150). People above 90 years are highly susceptible to Alzheimerââ¬â¢s disorder.Among this, those who have Alzheimerââ¬â¢s history in their family are 90 % prone to this disorder. Protective Factors Apart from the biological factors there are various other factors that influence the onset of Alzheimerââ¬â¢s disease. Various protective factors that are powerful enough to delay the commencement of Alzheimerââ¬â¢s disorder have been discovered. For example, Genetic endowment with the ApoE-e2 allele is capable of reducing the risk of Alzheimerââ¬â¢s disorder (Duara et al. , 1996). The exact role and the original mechanism of action of ApoE-e2 allele, however, are not com pletely understood.Deep thinking, higher educational level and wisdom are also proved to be associated with the delay in the commencement of Alzheimerââ¬â¢s disease (Stern et al. , 1994; Callahan et al. , 1996a). Few medication and drugs are also found to be good for delaying the onset of Alzheimerââ¬â¢s disorder. For example, medications, like nonsteroidal anti-inflammatory drugs (Andersen et al. , 1995; McGeer et al. , 1996) and estrogen replacement therapy (Paganini-Hill & Henderson, 1994), are found to be effectively delaying the commencement of Alzheimerââ¬â¢s disease.Apart from this, Vitamin E and the drug selegiline (otherwise known as deprenyl) are also proved to holdup the crucial stages of the course of Alzheimerââ¬â¢s disorder, for example the nursing home placement, serious functional impairments or disorders as the disease progresses and lead to death (Sano et al. , 1997). According to Behl et al. , 1995, the course of action of the protective agents in a pe rson is not completely known; however, these agents are proved to check the toxic action of oxidative stress (through antioxidants like vitamin E or estrogen).These agents also counter the work of inflammatory mediators related to plaque formation (through anti-inflammatories) (Mark et al. , 1995). Histopathology The pathophysiology of Alzheimerââ¬â¢s disorder is also proved to be associated with the histopathologic variations in Alzheimerââ¬â¢s disease. These histopathologic changes include neuritic plaques, synaptic loss, neurofibrillary tangles, hippocampal granulovacuolar degeneration, and B amyloid angiopathy (Cummings et al. , 1998b).Majority of the genetic and epigenetic risk factors are some or the other way linked with B amyloid. This has helped the medical researchers to conclude that the formation of B amyloid peptide is the most crucial pathological event or step in the course of spread of Alzheimerââ¬â¢s disorder in a person (Cummings et al. , 1998b; Hardy & Hi ggins, 1992). A successful intervention in the course of Alzheimerââ¬â¢s disease spreading may include get in the way of any of the numerous steps included in the slow progress of Alzheimerââ¬â¢s disease pathogenetic cascade.Few of the intervention modes include intervening to reduce B amyloid generation from the amyloid precursor protein, intervening to decrease the B amyloid aggregation as well as the generation of beta-pleated sheets, and intervening in the amyloid-related neurotoxicity process. Successful interference in these steps may help interrupt Alzheimerââ¬â¢s spread. Apart from this, few therapies can successfully block the neuronal cell death and can slow down the inflammatory response occurring in neurotic plaques.Therapies are also proved to inhibit the work of certain growth factors and hormones and also delay the replenishment of deficient neurotransmitters. As the complete obstruction of the processes within the B amyloid cascade may affect the usual cereb ral metabolic processes, successful interruptions may bring about partial interruptions (Cummings & Jeste, 1999). Studies about the molecular neuroscience of Alzheimerââ¬â¢s disease have researched several crucial aspects of pathophysiology and etiology.Researchers are working to thoroughly understand the entire processes and reasons behind cell death, neuronal degeneration and subsequent memory degradation. Medical world is expecting new revelations from these studies and are on the way to lay a new therapeutic path for eliminating Alzheimerââ¬â¢s disease from the world (National Institute on Aging, 1996). Medical world is expecting researchers to come out with the real physiological factor that makes a human body prone to Alzheimerââ¬â¢s syndrome. Role of AcetylcholineAcetylcholine is also suspected to play a part in encouraging Alzheimerââ¬â¢s disorder in a person. Loss or decrease of the neurotransmitter acetylcholine also is proved to be responsible for the pathogen esis of Alzheimerââ¬â¢s disease. Postmortem researches in Alzheimerââ¬â¢s disease infected people have explained the loss or reduction of basal forebrain and cortical cholinergic neurons and the exhaustion of choline acetyltransferase, which is the enzyme that carry out acetylcholine synthesis (Mesulam, 1996). Several post mortem reports have come out with the same reason.The scale of this central cholinergic deficit is associated with the severity of dementia that results in the ââ¬Ëcholinergicââ¬â¢ hypotheses of cognitive deficits in Alzheimerââ¬â¢s disorder (Mesulam, 1996). This hypothesis and the clinical researches have proved that Acetylcholine play a major role in Alzheimerââ¬â¢s disease. However, acetylcholine is not the only neurotransmitter that encourages the growth of Alzheimerââ¬â¢s disorder in a patient. Researchers are still working to find out the role of other substances in the pathogenesis of the Alzheimerââ¬â¢s disorder.The researches relat ed to the pharmacological treatment of this syndrome are coming out with new results. It has been proved that a delay or break in the spread of Alzheimerââ¬â¢s disease is proved to reduce its prevalence in the body of a patient even by half (Breitner, 1991). In order to inhibit the spread of this syndrome in a person it is necessary to delay the onset of the disease to such an extent where mortality from other resources surpasses the frequency of the steps of the disease.So the most crucial step in inhibiting Alzheimerââ¬â¢s disease is the identification of the factors that stop the onset or slow down the progress of the disease in the patient. Working on these agents would help reduce the spread of the disease. References Aarts, P. , & Op den Velde W. (1996). Prior traumatization and the process of aging. In B. A. van der Kolk, A. C. McFarlane, & L. Weisath (Eds. ), Traumatic stress: The effects of overwhelming experience on mind, body and society (pp. 359ââ¬â377). New Yo rk: Guilford Press. Abrams, R. C. , Rosendahl, E. , Card, C. , & Alexopoulos, G. S. (1994).Personality disorder correlates of late and early onset depression. Journal of the American Geriatrics Society, 42, 727ââ¬â731. Adams, W. L. , Garry, P. J. , Rhyne, R. , Hunt, W. C. , & Goodwin, J. S. (1990). Alcohol intake in the healthy elderly. Changes with age in a cross-sectional and longitudinal study. Journal of the American Geriatrics Society, 38, 211ââ¬â216. Aevarsson, O. , & Skoog, I. (1996). A population-based study on the incidence of dementia disorders between 85 and 88 years of age. Journal of the American Geriatrics Society, 44, 1455ââ¬â1460. Aiken, L. (1990). Chronic mental illness. In B. S. Fogel, A. Furino, & G.Gottlieb (Eds. ), Mental health policy for older Americans: Protecting minds at risk. Washington, DC: American Psychiatric Press. Albert, M. S. , Jones, K. , Savage, C. R. , Berkman, L. , Seeman, T. , Blazer, D. , & Rowe, J. W. (1995). Predictors of cogniti ve change in older persons: MacArthur studies of successful aging. Psychology and Aging, 10, 578ââ¬â589. Alexopoulos, G. S. (1997, November 6). Epidemiology, nosology and treatment of geriatric depression. Paper presented at Exploring Opportunities to Advance Mental Health Care for an Aging Population, meeting sponsored by the John A. Hartford Foundation, Rockville, MD.
Subscribe to:
Post Comments (Atom)
No comments:
Post a Comment
Note: Only a member of this blog may post a comment.