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Analysis of atrophy in Alzheimers disease using voxel-based morphometry

By B. Kemp

Abstract

About half of all dementia patients are Alzheimer’s Disease (AD) cases . One of its risk factors being aging, dementia prevalence is only expected to grow. Compared to other types of dementia, AD can be characterized by increasing problems revolving around learning and information retaining (think calculation, language, purposeful behaviour, visuospatial skills). The disease is marked by large quantities of extracellular neuritic amyloid plaques (accumulations of insoluble fibrous proteins in grey matter) and intraneuronal neurofibrillary tangles (accumulations of intertwined hyperphosphorylated tau-proteins; insoluble as well) that obstruct neuronal metabolism, communication and repair, eventually leading to cell death. It is not known whether the plaques are causes or byproducts of AD. The tangles are also found in other so-called tau-opathies, like frontotemporal dementia (FTD) and corticobasal degeneration (CBD), and in “virtually everyone” by the age of 85. In essence, AD is an uneven, progressive loss of neurons (atrophy). With the progression of the disease, different (especially memory related) problems arise that may be summed up by amnesia, apraxia, agnosia and aphasia. The first structures to be affected in AD, lie within the medial temporal lobe (MTL), a small but crucial node: the entorhinal cortex and hippocampus. The volumes of these structures are considered to have high sensitivity and specificity in detecting AD. From there on, the atrophy spreads throughout and beyond the MTL, eventually affecting the entire brain (although the temporal lobe remains the heaviest affected). An early detection of AD is very important, since potentially diseasemodifying drug therapy has become available. Likewise, insight into the progression of the disease may be very helpful in the development of preventive strategies. Brain abnormalities may precede a clinical diagnosis by many years (Fox et al state a minimum of three years of subtle memory deficits and atrophy rate increase before diagnosis; tangle formation may initiate as much as 50 years before symptoms occur), and a definitive diagnosis of AD can only be established histologically. Nevertheless, in vivo analyses of AD affected brains can be performed by the use of functional neuroimaging modalities such as SPECT and PET. As the clinical symptoms are not directly caused by the plaques and tangles, but rather by the loss of neurons (and their connections with other neurons), assessing AD can be done by examining atrophy. This may be carried out indirectly, e.g. via resting glucose consumption in PET; or directly, using CT or MRI. When processing MRI data, the gold standard is considered to be region-of-interest (ROI) based. The main objections to such a (semi-)manual method are its time consumption and likely bias, as it involves a human operator. By the same token, reproducibility is a problem. A different approach exists: voxel-based morphometry (VBM), which is an automatic, wholebrain (and therefore, unbiased) procedure that can be used to process MRI data in order to analyse atrophy. This study aims to give an overview on the use of the powerful yet quite straightforward method of VBM in investigating AD. Clinical results of different studies are compared among each other

Topics: Geneeskunde, Alzheimer's Disease, Atrophy, Brain Imaging, Image Registration, Image Segmentation, Voxel-Based Morphometry
Year: 2009
OAI identifier: oai:dspace.library.uu.nl:1874/31949
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