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Alzheimers Disease

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Alzheimer is a form of dementia that affects around 5.3 million people in the world. The sheer magnitude of the people it affects implies the urgent need to improve on the diagnosis and treatment of the disease. Neuroimaging approaches such as magnetic resonance imaging (MRI) and many others have significantly improved the diagnosis of the disease. Studies on the neuroimaging approaches imply that diagnosis on various parts of the brain is possible. It is now possible to diagnosis accurately Alzheimer’s disease at the mild cognitive impairment (MCI) stage. However, continues research and improvement on the area should be emphasized to improve further the steps achieved.

Alzheimer’s is a common cause of dementia. It mostly affects the aging population. It is a condition that results in progressive destroyable of neurons with a subsequent damage to the connection to the brain. This leads to loss of cognitive function of the body ultimately causing death. Estimates show that around 5.3 million people in the world suffer from the disease. They further suggest that people suffering from the disease will increase over the coming years. Alzheimer is the leading cause of death and financial resources in the United States and other parts of the world alike, compared to other causes of dementia. The number of deaths is probably going to continue rising if a therapeutic approach for early detection is not designed. It has also resulted in financial losses as Medicare to the patients takes around $100 billion a year.

Approaches to Neuroimaging

It is crucial for continuous research on the area to fill the knowledge gap. The general population should access information on the disease, so as to know the symptoms and seek treatment early. Diagnosis can be achieved through structural and functional magnetic resonance imaging or 18F-FDG PET. However, there are other methods such as PET and DTI. The first characteristic of Alzheimer’s disease is amyloid deposition and intertwining of the neuron fibers. It also shows itself through loss of cortical neurons and synapses. Cholinesterase inhibitors are able to delay the development of Alzheimer’s disease. Therapeutic interventions are, however, necessary for diagnosis of the disease through longitudinal enquiries and early diagnosis.

Biomarkers are also vital to the study of Alzheimer. Biomakers serve to improve the accuracy of the diagnosis. They also serve as a substitute endpoint of illness severity. The often used biomarkers include PET, MRI and SPECT. High spatial resolution in neuroimaging processes such as structural MRI has made it possible investigations. They are not only the cortical, but also sub cortical regions. PET has advantages over SPECT during diagnosis as expressed by Silverman due to higher sensitivity and spatial resolution. The advantages of using SPECT are cheapness and its availability.

However, both 18F-FDG PET and SPECT are effective in reducing lesions in the tempororoparietal cortex. The diagnosis from both methods is similar. There is a difference noted between the two methods. SPECT brain’s perfusion is similar to the histopathologic changes in the spread of neurofibrillary pathology of patients suffering from Alzheimer’s disease.

Volume of interest (VOI) has received recognition as a viable method. Its weaknesses are that it leaves large part of the brain unobserved. It is up to the person carrying out the diagnosis to decide the part of the brain he wants to observe. A stereotactic approach of voxel by voxel analysis is the preferred method. This is because of the advantages of an investigation that generates data and is not appealing to the subjectivity of the individual carrying out the diagnosis.

Longitudinal and cross sectional analysis usually employs statistical parametric mapping (SPM) applications in neuroimaging research for dementia suffering individuals. The application usually permits anatomic synchronization of data generated from PET and SPECT. Three dimensional surface projections can also be used in the analysis of data generated from SPECT or PET. It is advantageous because it is possible to carry it out without structural image data. It compensates for the errors made in anatomical standardization, in statistical parametric mapping (SPM) analysis, by collecting primary data from the medial and lateral brain surfaces itself. The method is also advantageous because it reduces the collaborative effect of brain atrophy and fractional image averaging on the images. In cross sectional studies of dementia cases, researchers usually use 3D-SSP.

Magnetic resonance imaging (MRI) is among the most crucial methods employed in neuroimaging. It is used in diagnosis of dementia especially Alzheimer’s disease. MR images, however, do not offer a chance for evaluation of mild atrophy of regions of the brain affected by, the Alzheimer’s disease by just visual observation. Its weakness is that it is subjective to the knowledge of the person examining the data and due to its time consuming nature. The automated substitute of volumetric MRI, voxel-based morphometry (VBM) is objective and highly accurate. The method is unbiased compared to the methods. The initial VBM method had three processes anatomic standardization, segmentation and smoothing of the images.

Alzheimer’s disease is not common in people between the ages of 60-64 years. Only 1% of the population between the years reports the case of Alzheimer. However, the prevalence rate increases rapidly as we approach the age of 85 years. About 24% to 33% report cases of dementia. It is more prevalent in women with a 70% chance than men of suffering from the disease. Neuroimaging results can be used to analyze the relationship between aging and a reported case of suffering from the disease. Studies have revealed that there may be a constructive connection between partial volume correction (PVC) and aging, while others have realized a negatives correlation. Improvement in technology has made it possible to PVC on images realized from PET and SPECT possible. These are studies to find out the age of a person and his gray matter volume. They attempt to find out the rate of preservation of grey matter in amygdale, hippocampus, thalami and entorhinal regions of the brain.

According to data from SPECT and PET, Women have a grey matter concetraion in the left minor anterior gyrus, bilateral middle chronological gyri and left superior chronological gyrus. Men have a higher gray matter concentration in the right superior parietal lobule, left superior frontal gyrus, right postcentral gyrus, right cerebellum, right middle frontal gyrus, right precuneus and right fusiform gyrus.

Persons with mild cognitive impairment (MCI) are at risk of developing into Alzheimer’s disease. These individuals complain of memory loss but have not reached the threshold of diagnosis with Alzheimer’s disease. Heterogeneous or amnetic MCI develop into Alzheimer, causing memory loss, cognition defects and inability to perform daily chores. Early diagnosis of the Alzheimer’s disease, when it is at the mild cognition impairment stage, can help to prevent the disease from developing. It could be beneficial in lowering the victims of the disease.

Researches to help in early diagnosis of the Alzheimer’s disease at the mild cognitive impairment have identified areas that could be used to achieve it. An early sign of the disease is the reduction of blood flow in the parietotemporal association cortex. The posterior association cortex is identified by researchers as the first area to be affected by the illness. It continues to spread over time to the fronatal lobes. The posterior association cortex is most affected in patients that are suffering from mild cognitive impairment. It will then eventually develop into Alzheimer than in patients suffering from developed Alzheimer’s disease. Patients with late-onset disease have primary motor sensory and visual cortices are most affected compared to the early onset disease patients.

Using PET or SPECT has realized that in early diagnosis can be made by observing the glucose metabolism in the posterior cingulate gyrus and precuneus. However, the gray matter in the patients remains the same. Its characteristics are brain perfusion that results in an increase, in the cerebral fluid space. In order to obtain a clear observation, we use three dimensional statistical stereotactic projections to obtain the image. It is more accurate in investigative studies at the posterior cingulate gyrus and precuneus than in the medial temporal areas, parietal association cortices or the temporal association cortices. This has shown that the pathophysiologic process of cognition decline begins early, as indicated by the reduction in metabolism. This shows the lateness of clinical detection of dementia in relation to the process of metabolism reduction.

Observations in primates with the exception of humans show that the entorhinal cortex is the earliest to show signs. The signs include lesions; with a decline in metabolism next that is significant and long lasting at the inferior parietal, posterior temporal, posterior cingulate and occipital association cortices. However, the parts of the brain affected by this decline in metabolism are small and remote. 18F-FDG PET has shown that some functional connectivity exists between the entorhinal cortex and the posterior cingulate gyrus in patients with Alzheimer.

Studies by the longitudinal SPECT have shown that decrease in metabolism in the posterior cingulate gyrus and precuneous become non-important as the disease progresses from MCI to Alzheimer. This is due to the high metabolism in these areas than in the other cortical regions. Memory control is by the posterior cingulate gyrus.  The retrosplenial cingulate cortex receives assistance from the projects to the anterior thalamus, and the subiculum. They association provide a secondary route through the thalamus and the hippocampus. Lesions in this region cause memory dysfunction as they cause distortions to the above pathway.

There are insufficient studies on the functions and connectivity of precuneus. However, anatomic evidence suggests that there is a connection to the occipital, thalamus, temporal and the prefrontal. The precuneous is crucial in memory retrieval, but it does not control the memory task itself.

Another region that can use for early detection of Alzheimer’s disease is the medial temporal areas. The amygdale and hippocampus have high atrophy during the start of the Alzheimer’s disease. Earlier studies using SPECT showed reduced metabolism in the hippocampus. However, later studies using PET with higher spatial resolution did not derive the same results. This may be attributed to the partial volume effect on images derived by SPECT. The PET measure is most accurate at the entorhinal cortex in detection of individuals suffering from mild cognitive impairments.

Researchers, who have employed magnetic resonance imaging based on the selected area of interest, have reported that to be a reduction in glucose metabolism in the hippocampus. VBM, May, however, not be able to show variations in relatively small regions. Therefore, it is unlikely to use it to detect changes in the glucose metabolism at the hippocampus. The main reason for this is because of failed spatial alignment. PET with a higher resolution and little effect on partial volume is the most effective.

Atrophy on the medial temporal lobe is a sign of Alzheimer’s disease. Structural MRI has shown that a decrease in the entorhinal cortex volume with deposits of tangle which move to the hippocampus, as a definitive early sign of Alzheimer’s disease. The entorhinal cortex is the earliest region of the brain to be affected by the disease characterized by plaques and neuron fibers tangles. The neuropathology studies come to the above conclusion. The medial temporal areas also show significant reduction in grey matter. A VBM study by Barrow et al showed a significant decrease in the grey matter at the bilateral medial temporal areas (Barrow, 2007). This study showed that VBM could be used in detection of unusual early Alzheimer’s disease. However, recommendation is that care ought to be taken in this region during diagnosis. The patients with the mild cognitive impairment reported excessive loss of gray matter in the parietal cortex, posterior cingulate gyrus, and precuneus.

Approach Prediction from MCI to Alzheimer

The accuracy of prediction of conversion of MCI to Alzheimer’s disease using neuroimaging studies is extremely crucial. 18F-FDG PET study showed a high prediction in the parietal association regions compared to the posterior cingulate gyrus. It also reported a low glucose metabolism in the inferior parietal cortex. A longitudinal study using 18FDG PET reported a high prediction rate of function variations in the posterior cingulate gyrus (Van, 2010). A study using SPECT revealed that there was low rCBF in the bilateral parietal areas and precunei. It also showed that converters had low rCBF at the parietal and temporal lobes, precuneus and posterior cingulate cortex.

MRI studies to find out the volume of entorhinal cortex and hippocampus revealed that the volume in the entorhinal was accurate in measuring the individuals who would suffer from Alzheimer. In the hippocampus, the MRI measures were not accurate as not all the individuals under study developed dementia over time (Pennanen, 2004). There were reports of High loss of gray matter at the hippocampus region, inferior and middle temporal gyri, posterior cingulate gyrus, and precuneus.

Conclusion

The neuroimaging approaches to studying Alzheimer’s disease, have been crucial in early detection of the disease and, therefore, led reduced number of deaths due to it. PET, structural and functional MRI, SPECT and other neuroimaging approaches have played a key role in diagnosis, differentiation of Alzheimer’s disease from other forms of dementia, accessing therapeutic options and finding out the predictive value of MCI to Alzheimer’s disease of each approach. They are vital in diagnosing Alzheimer’s disease at the mild cognitive impairment stage so as to treat it early. Finally, improvement in the neuroimaging approaches over the years, has improved the diagnosis and other variables associated with dementia.

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