The hippocampus is a major component of the brain which belongs to the limbic system. It is responsible for the high learning abilities and primitive emotions in humans. It is a part of the cerebral cortex located on both the hemisphere of our brain. In the case of Alzheimer's disease, the hippocampus is one of the first regions of the brain to suffer damage and memory loss. This remarks the early symptoms of the disease. The conditions such as, hypoxia, amnesia, epilepsy, etc affects hippocampus adversely.

The early detection of hippocampal distortion can help in the treatment of the age-related problems like, Alzheimer's disease, memory loss, amnesia, etc. The non invasive fMRI technology can detect the shrinkage of the hippocampus in elderly people without any pain. This is a sign of great relief for millions of people suffering from the neurodegenerative disorder worldwide. The different phases of the clinical research are being executed to prove the safety and efficacy of this non- invasive imaging technology. The clinical research included the patients with Alzheimer's, patients with mild cognitive impairment (MCI) and normal adults as a control. The multi-voxel 31P labelled magnetic resonance spectroscopy (MRS) imaging along with an advanced analytical tool was used on the subjects to assess their neuro-chemistry in the hippocampal regions. The results showed that the left hippocampus becomes alkaline in AD patients, which is in contrast to the normal aging process in which the brain tends to be more acidic in nature. Along with the increase in pH, there is a significant change in four other chemicals in the brain of pre-Alzheimer's and Alzheimer's patients compared to normal subjects. These chemicals are phosphomonoester (PME) which is the building block of neuronal membrane, phosphodiester (PDE), the membrane degradation product; phosphocreatine (PCr), the stored energy utilised for the functioning of our brain and adenosine triphosphate which is the main source of brain energy. We can observe a significant reduction in the level of phosphomonoester (PME) and remarkable increase in the phosphodiester, phosphocreatine and ATP in the left hippocampal region of these patients.

Besides that, Glutathione, an anti-oxidant agent is found in the major organs of the body including the brain. It eliminates the toxic metal ions produced in the body. Due to some environmental or genetic factors, excess of zinc ions are produced in the body which causes neurotoxicity. This leads to Alzheimer's disease and dementia. During AD (Alzheimer's disease) the level of glutathione is depleted in the brain. The researchers have found that MRI (Magnetic Resonance Imaging) can detect the level of glutathione. So this can help in the early diagnosis of AD which is a sign of great relief for the patients.

Glutathione can be the possible biomarker for Alzheimer's disease and MRI scans are essential in monitoring its level in the specific regions of brain. Though, PET (Positron emission tomography) is one of the most advanced and sensitive technology for making an early diagnosis of AD but its high cost and limited availability has increased the demand of MRI (magnetic resonance imaging). However, the accuracy of structural MRI as biomarker of early AD diagnosis generally reaches an accuracy of 80%, so additional biomarkers is used to improve the predictions. Other structural MRI (diffusion weighted, diffusion-tensor MRI) and functional MRI have also added interesting contribution to the understanding of the physiology of AD.

Functional magnetic resonance imaging (fMRI) is a non-invasive technique that scans the 3D image of the metabolic activity within the anatomical structure of the human brain. With the help of fMRI, the scientists have identified the presence of anatomically distributed regions operating as large-scale neural networks which are observed both during the performance of associative memory tasks and in the dormant state. The progress in the utility of task-related and task-free MRI is studied to elucidate the changes in neural activity of normal adults and patients of Alzheimer's disease. These two groups of task-free MRI and task-based fMRI may prove useful as non-invasive biomarkers in studying the progression of dementia during the Alzheimer's disease.
The focus of most of the research on Alzheimer's disease in the last decades has been on senile plaques and neurofibrillary tangles. The vast majority of patients with Alzheimer's disease are over 75 years of age. To consider the old-age dementia as a homogenous well-defined condition we need to ignores the complexity of this condition and limits the development of new diagnostic methods, preventive strategies, or treatment strategies that could be widely applicable in daily practice in the majority of the older patients. The biomarkers focusing on the correlation of plaques and tangles does not work in the older dementia subjects. Knowing the fact that the dementia in old age is a different condition from dementia at relatively younger age, different approached of research must be implied for the two different generations.

Oxidative stress has a major role in the study of brain disorders where implementation of ATP is always high. The Brain type Creatine Kinase (BB-CK) facilitates the transfer of high energy phosphoryl group from Phosphocreatine to Magnesium-ADP to regenerate ATP, which is the main source of chemical energy in the brain. The reactive aldehyde 4-hydroxy-2-nonenal (4-HNE) is also generated due to lipid peroxidation arising from oxidative stress and thus 4-HNE is subsequently increased in the patients. It was also reported that the levels of 4-HNE increase with statistical significance in the amygdala, the hippocampus and the para-hippocampal gyrus, in AD patients. Such increased oxidative stress was recently tested by measuring the major antioxidant glutathione from the hippocampal areas, where the level of glutathione was found to be depleted in hippocampal areas of AD subjects.

Hippocampus plays an important role in normal cognitive functions of our brain. The significant chemical and functional changes are observed in the left and right portions of hippocampus in the AD patients. The observation after the study suggests that the normal subjects did not show any cognitive decline, though there was a slight tendency in hippocampal atrophy. The atrophic change of the left hippocampus is considered to be a good biomarker for the very early stage of the neurodegenerative disorder.

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Geetanjali Murari
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