Alzheimers disease and Its Neural Correlates - Essay Example

Alzheimer’s disease and Its Neural Correlates s : Introduction Today, one of the major prevalent health problems is dementia .There is rapid increase in the number of people being diagnosed with dementia at a global scale. Alzheimer’s disease is one most common forms of dementia and is caused to neurodegeneration. It is primarily found among the ageing population. This neurological ailment leads to death of brain cells which eventually leads to loss of memory and cognitive functioning of the brain. Researchers have primarily focused on understanding the prototypical neural correlates of the diseases since the disease particularly affects the neural networks. Neural correlates Several studies have tried to understand the disease by utilizing the method of neuroimaging since neuroimaging is extremely accurate. Most of the studies have concentrated on understanding the reasons behind the delusions that are elicited. Ismail et al (2002), presented a review paper where 23 such studies have been thoroughly reviewed. Majority of the studies have concluded right sided pathology with special emphasis on the frontal lobe.” Left-frontal predominance and release, secondary to right-sided pathology, may create a hyperinferential state resulting in the formation of delusions” and such imbalances that arise in normal neural networking has been associated with the delusions. Different neural substrates have been shown to be associated with delusional problems such as paranoia and misidentification. Trail-Making Test on 20 subjects showed that executive functioning is impaired in patients with AD (Hunt et al,2011). Positron emission tomography along with neuropsychological testing established that different TMT tests could be correlated to glucose metabolism primarily in the frontal lobe. One of the major problems that have been associated with the disease is language problem. Scientists have tried to identify the relation between neural correlates and the problem of language such as naming and fluency. Several studies had been conducted on subjects to understand the phenomenon and Melrose et al (2009) conducted an experiment on 60 patients with potential Alzheimer’s diseases to help associate the disease to language impairments. The subjects were assessed using the Boston naming Test with FAS and semantic fluency. Phonemic cuing was used for extra words that had been stated. The results revealed that owing to hypermetabolism in the inferior temporal lobe region, subjects were unable to name a particular object; however it was seen that when phonemic cue was used there was higher metabolism in the inferior frontal gyrus, superior frontal lobe, left temporal and occipital areas leading to better performance during naming. Semantic problems could also be related to hypometabolism in the inferior frontal gyrus. Hence, the language problems that have been associated with the disease is related to the growing compromise between the frontal regions and the temporal regions. Nomura et al (2012) classified various delusions according to their neural correlates in patients suffering from AD. By investigating several indices of verbal language and metabolism of the cortex, the researchers tried to derive an association between neural correlates and ability to name.The researchers selected outpatients who were diagnosed with AD. Using the Neuropsychiatric inventory delusions of 87 patients was classified. In order to relate the classification to different neural correlated 25 of the 87 subject underwent I-IMP SPECT imaging. The imaging helped the researchers see the hypoperfusion in the right temporal lobe and hyperperfusion in the medial and precentral regions of the brain and associate them to different correlates. The results helped the researchers establish that delusions could be classifies into three factors (i.e. I,II and III) and that the three different classification were related to different neural networks. Factor I was associated with hypoperfusion the right temporal region and hyperperfusion the medial frontal and presentral regions of the brain. Factor 1 was based on the delusions of sudden abandonment, phantom border syndrome and believing that one’s spouse is not what one claimed to be. Factor 2 delusion was television and delusion of persecution. Factor 2 was mostly related to hyperpefusion in the thalamus and hypoperfusion in the precuneus region. Factor 3 was primarily delusion of abandonment and jealousy and it was associated with hypoperfusion in the right inferior temporal and frontal regions while hyperperfusion was seen in the frontal gyrus and posterior cingulate gyrus regions. Besides language problem cognition is also impaired and there is rapid declination in the though processing ability of the brain. In fact AD forst appears as mild cognitive impairments in the patients which then advances with time and the symptoms become more severe. Attention deficiency is also a clinical manifestation of this problem. Van Dam et al (2013) studied the results obtained from magnetic resonance imaging (MRI) of 8 subjects and compared the differences in the brain activity during attention tests. The results showed that whilst in normal people there was no significant difference in brain activity people with mild cognitive impairment showed “activity in neural regions typically associated with the networks subserving these functions (e.g., temporoparietal junction and posterior parietal regions, respectively)” (Johnson et al,2013). The results vindicated the fact that attention deficiency is present in patients of mild cognitive impairment and the problem may advance into AD during the later stages of life. A similar study meta-analysis was conducted by Schroeter et al (2009) to revel the neural correlates of AD and its prodromal stage. The study was mostly based on review of similar studies. “The meta-analysis reveals that early Alzheimers disease affects structurally the (trans-)entorhinal and hippocampal region, functionally the inferior parietal lobules and precuneus” (Schroeter,2009). Changes in the postulate cingular cortex and in the precuneus are not very specific however, changes particularly atrophy in the entorhinal area or in the hippocampus region or hypoperfusion/hyperperfusion in the parietal lobules give rise to mild cognitive impairment which progresses to AD. It is obvious that a degenerative disorder such as AD will have cognitive declination; however it needs to be remembered that it also affects the independence of a patient. The independence of an individual primarily rests on the cognitive functioning and physical ability of a person. Vidoni et al (2011) assess the neural imaging of participants and found an association between “ADCS-ADL, COG), and PPT in nondemented older adults and individuals with early AD” (Vidoni,2011). Therefore loss of independence in the early stages is seen and has been associated to cognition loss as well. Pathophysiology Neuronal network models have been handy in understanding the different systems of the brain and also investigating the individual networks. Such neuronal networks models have been used to attain an understanding of the pathophysiology of AD. Abuhassan et al (2012) used a 200 neuron and a 1000 neuron model. The disruption of the beta band power of the models is assessed and compared to EEG studies of AD patients. A large difference is seen where a rapid decrease in beta band power is seen in the early stages of the diseases while an increases in the theta band power is noticed. Therefore, the first component to be affected is the beta band power when there is decrease in neurons in the circuit. Besides models, several studies have shown that “excitatory and inhibitory synaptic circuits in the cortex and hippocampus as key cellular substrates of pathogenesis” (Penzes et al,2013) in neurodegenerative disorders such as AD. Prior to this not much attention was given to pshycosis that accompanied AD. AD patients with Psychosis showed greater declination in cognitive functioning than those patients who did not have psychosis. Most studies suggest the existence of a specific neurobiology behind the presence of psychosis in AD. Genetic inheritance has also been stated as one of the most important reasons since in almost 61% cases psychosis in AD is an inherited trait. The strongest correlate of AD is perhaps loss of synapse. Neuroimaging of AD patients has revealed that in individuals with additional psychosis showed greater disruption in the gray region of neocortex. Pathophysiology studies of patients also show that Kalirin, a dendritic protein is present in greater amounts in patients who have AD and psychosis together giving rise to abnormal synaptic pathology. TRAUMATIC BRAIN INJURY The cranium is intended to protect the brain from shocks and injuries however in some cases accidents and other traumatic injuries harm the brain. Both mild and severe forms of accidental injuries to the brain have their own implication however the most common implication is death of brain cells. Traumatic brain injuries (TBI) are known to have both acute and chronic effects and also are known to cause neurodegeneration. Statistical studies have found an important link between the history of a traumatic brain injury and onset of Alzheimer’s and that such an injury accelerates onset of AD among patients. Johnson et al (2010), have investigated the pathological link between brain injury and onset of AD. It has been seen that patients with TBI develop a plaque in the brain similar to those with AD. Examinations of the human brain has revealed that in TBI patients axonal plaque is seen o occur shortly after the accident and in the long-run it leads to neurodegeneration and in most cases culminates into AD. Immunohistochemical findings have shown the amyloid-beta plaques found in AD patients are almost similar and therefore it could be said that a TBI is followed by accumulation of amyloid protein in the damaged axons which with age gives rise to amyloid-beta plaque which is an important hallmark of AD. Following a traumatic injury the amyloid pathology is affected by the lipid transport protein- apolipoprotein E (APOE). Genetic analyses have shown that individuals who have had a brain injury and also carry the APOE e4 allele had greater chances of developing the beta amyloid plaque. CONCLUSION Alzheimer’s disease, the most common forms of dementia is progressively becoming a health problem. Enhanced understanding of the disease with thorough knowledge about the pathophysiology of the disorder will help design proper management and diagnostic plans. The disorder is mainly concerned with neural correlates and thorough research is needed to understand how different neural systems and their functioning are altered in a patient suffering from AD. Valid screening processes and better approaches to interventions and therapies has become more easy to design given to the fact that various researchers have focused on understanding the neural correlates of the diseases especially during the it’s earlier stages. Imaging of the brain and the neural system also helps understand the alterations more accurately and therefore more research should be oriented towards understanding neuronal modeling, interpretation of imaging and resultant physiology of neural correlates of the disease. Greater advancement in the this field would help in early diagnosis of since most of the dementia- related diseases are diagnosed at latter stages and hence early diagnosis is really necessary for successful therapeutic interventions. REFERENCES Abuhassan, K., Coyle, D., & Maguire, L. P. (2012). Investigating the Neural Correlates of Pathological Cortical Networks in Alzheimers Disease Using Heterogeneous Neuronal Models. IEEE Transactions On Biomedical Engineering, 59(3), 890-896. doi:10.1109/TBME.2011.2181843. Hunt, A., Haberkorn, U., Schröder, J., & Schönknecht, P. (2011). Neural correlates of executive dysfunction in prodromal and manifest Alzheimer’s disease. Geropsych: The Journal Of Gerontopsychology And Geriatric Psychiatry, 24(2), 77-81. doi:10.1024/1662-9647/a000038. Ismail, Z., Nguyen, M., Fischer, C. E., Schweizer, T. A., & Mulsant, B. H. (2012). Neuroimaging of delusions in Alzheimer’s disease. Psychiatry Research: Neuroimaging Section, 202(2), 89-95. Doi:10.1016/j.pscychresns.2012.01.008 Johnson, V. E., Stewart, W., & Smith, D. H. (2010). Traumatic brain injury and amyloid-β pathology: a link to Alzheimers disease?. Nature Reviews Neuroscience, 11(5), 361-370. Melrose, R. J., Campa, O. M., Harwood, D. G., Osato, S., Mandelkern, M. A., & Sultzer, D. L. (2009). The neural correlates of naming and fluency deficits in Alzheimers disease: an FDG-PET study. International Journal Of Geriatric Psychiatry, 24(8), 885-893. doi:10.1002/gps.2229. Nomura, K., Kazui, H., Wada, T., Sugiyama, H., Yamamoto, D., Yoshiyama, K., & . Takeda, M. (2012). Classification of delusions in Alzheimers disease and their neural correlates. Penzes, P., Buonanno, A., Passafaro, M., Sala, C., & Sweet, R. A. (2013). Developmental vulnerability of synapses and circuits associated with neuropsychiatric disorders. Journal Of Neurochemistry, 126(2), 165-182. doi:10.1111/jnc.12261. Schönknecht, O., Toro, P., Hunt, A., Henze, M., Haberkorn, U., & Schröder, J. (2011). Neural Correlates of Cognition Deficits in Mild Cognitive Impairment and Alzheimers Disease. Mind & Brain, The Journal Of Psychiatry, 2(1), 1-8. Vidoni, E. D., Honea, R. A., & Burns, J. M. (2010). Neural Correlates of Impaired Functional Independence in Early Alzheimers Disease. Journal Of Alzheimers Disease, 19(2), 517-527. doi:10.3233/JAD-2010-1245 Psychogeriatrics, 12(3), 200-210. doi:10.1111/j.1479-8301.2012.00427.x Van Dam, N. T., Sano, M., Mitsis, E. M., Grossman, H. T., Xiaosi, G., Yunsoo, P., & ... Jin, F. (2013). Functional Neural Correlates of Attentional Deficits in Amnestic Mild Cognitive Impairment. Plos ONE, 8(1), 1-12. doi:10.1371/journal.pone.0054035 Read More