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One of the most pressing concerns for the future is the increasing demands on the healthcare system related to the rapidly aging population. A direct consequence of increased life expectancy is a greater number of people with neurodegenerative diseases such as Alzheimer's disease (AD). The hippocampal formation (HF) has been shown to be affected by aging and is one of the first structures involved in AD. The HF is not a homogeneous structure; it is composed of several substructures with different functions and cell morphology. Although many previous studies have examined the impact of aging and disease on the HF as a whole, few have examined how it affects the different substructures of the HF. The specific study of HF substructures is important because they are molecularly distinct and can be affected in different ways. Here we will try to better understand the FH and its subparts. We will take a three-pronged approach using the neuroimaging technique Magnetic Resonance Imaging (MRI): First, we will examine how the functional aspects of the different FH subparts are affected by aging and pathology. Specifically, we will examine functional MRI (fMRI) activity in the FH subparts in three different groups:
We will use high spatial resolution fMRI to detect activity in hippocampal subfields and employ a novel data analysis technique developed in our laboratory to examine connectivity within the hippocampus itself and between the hippocampus and the rest of the brain. fMRI activity will be induced through a novel language-domain cognitive task, which may provide insights into dynamic activity in the hippocampus. Second, we will study how the structural properties of hippocampal subfields are affected in the three groups, using high-resolution structural MRI. We will perform automated segmentation of hippocampal subfields to extract relevant quantitative measures of hippocampal subfields and analyze their interaction with age and pathology. Finally, we will attempt to integrate the two previous approaches by investigating the impact on cognition of age- and pathology-related structural changes in hippocampal subfields. Specifically, we will examine whether changes in structural measures of the functional hemisphere (FH) in the three participant groups are better predicted by performance on the novel language task or on standard memory tasks. This could lead to improved diagnostic tools for the early detection of Alzheimer's disease (AD). In summary, we use a multidisciplinary imaging approach to examine the substructures of the FH. Our hypothesis is that these structures are not equally affected by aging and pathology; this will become evident from our functional and structural images. If confirmed, our project will contribute to the understanding of the FH, enabling more targeted treatment options for aging and AD, as well as reducing the burden on the healthcare system.
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One of the most pertinent concerns for the future are the increased demands on the healthcare system by the rapidly aging population. A direct consequence of the increasing lifespan will be the larger number of people with neuro-degenerative diseases such as Alzheimer's Disease (AD). The Hippocampal Formation (HF) has been shown to be directly affected by the consequences of aging as well as being one of the first structures involved in AD. The HF is not a homogeneous structure, but is composed out of several substructures that have different projection targets and cell morphology. While many previous studies have examined the impact of aging and disease on the HF as a whole, few studies have examined how aging and disease affect the various subparts of the HF. A more fine grained study of the subparts of the HF is important because this may lead to more targeted treatment options. Here we will attempt to further understand the HF and its subparts by taking a three-pronged approach that relies on the neuro-imaging technique called Magnetic Resonance Imaging (MRI): First, we will examine how functional aspects of the different subparts of the HF are affected by aging and pathology. Specifically, we will examine functional MRI (fMRI) activity in the hippocampal subparts in three different populations:
We will use high spatial-resolution fMRI to detect activity in the hippocampal subparts, and will use a new data-analytic technique developed in our laboratory to examine the connectivity within the HF itself, and between the HF and the rest of the brain. FMRI activity was induced by a new cognitive task from the language domain that may provide insights about the dynamics of activity in the HF. Second, we will study how structural properties of the hippocampal subparts are affected in the three participant groups using high-resolution structural MR images. We will use automated segmentation of the hippocampal subfields to extract relevant quantitative measures of the HF subparts and examine their interaction with age and pathology. Finally, we will attempt to integrate the previous two approaches by investigating how aging- and pathology-related structural changes in hippocampal subparts have an impact on cognition. Specifically, we will examine whether changes in structural measures in the HF from across the three participant groups are better predicted by performance on the new language task, or by performance on standard memory tasks. This may lead to improved diagnostic tools for the early detection of AD. In summary, we use a multi-disciplinary high-resolution imaging approach to examine the substructures of the HF. Our hypothesis is that these structures are not equally affected by aging and pathology, and this will become evident from our functional and structural imaging studies. If confirmed, our project will contribute to our understanding of the HF and may result in more targeted treatment options for aging and AD and eventually reduce the burden on our system of healthcare.
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