Use of structural imaging to study the progression of Alzheimer's disease

Oxford Project to Investigate Memory and Ageing (OPTIMA), University Department of Pharmacology, University of Oxford, UK.
British Medical Bulletin (Impact Factor: 3.66). 08/1996; 52(3):575-86. DOI: 10.1093/oxfordjournals.bmb.a011568
Source: PubMed


Computed tomographic scans in the temporal lobe orientation are a valuable way of studying the medial temporal lobe. In patients with histopathologically-confirmed Alzheimer's disease the size of the medial temporal lobe is almost half that in age-matched controls and the rate of atrophy shown by yearly scans (15% per year) is 10-fold greater. Such a rapid rate of atrophy probably follows a catastrophic event in the brain indicating that Alzheimer's disease is distinct from accelerated normal ageing. The degree of medial temporal lobe atrophy is related to the density of neurofibrillary tangles in the hippocampus; it is a useful guide to diagnosis and has potential as a screening tool in populations. It is proposed that measurement of the rate of atrophy in asymptomatic individuals may be a predictor of Alzheimer's disease and could be used to monitor the effectiveness of therapies designed to retard the rate of neurodegeneration.

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    • "The HPF is the vital brain region involved in learning, memory and some suggest, particularly vulnerable to oxidative damage induced by inflammation [40,41]. Pathological changes reported in human brain specimens indicate that capillary and larger vessel disturbances occur within the HPF and precede the structural abnormalities that then develop within the temporal cortex and other regions of the brain [42-44]. The findings of previous studies demonstrating the potent effects of an SFA diet on BBB function principally within the HPF and of this study, showing the restorative effects of atorvastatin are therefore potentially of clinical relevance. "
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    ABSTRACT: Background Several studies have identified use of non-steroidal-anti-inflammatory drugs and statins for prevention of dementia, but their efficacy in slowing progression is not well understood. Cerebrovascular disturbances are common pathological feature of Alzheimer’s disease. We previously reported chronic ingestion of saturated fatty acids (SFA) compromises blood–brain barrier (BBB) integrity resulting in cerebral extravasation of plasma proteins and inflammation. However, the SFA-induced parenchymal accumulation of plasma proteins could be prevented by co-administration of some cholesterol lowering agents. Restoration of BBB dysfunction is clinically relevant, so the purpose of this study was to explore lipid-lowering agents could reverse BBB disturbances induced by chronic ingestion of SFA’s. Methods Wild-type mice were fed an SFA diet for 12 weeks to induce BBB dysfunction, and then randomised to receive atorvastatin, pravastatin or ibuprofen in combination with the SFA-rich diet for 2 or 8 weeks. Abundance of plasma-derived immunoglobulin-G (IgG) and amyloid-β enriched apolipoprotein (apo)-B lipoproteins within brain parenchyme were quantified utilising immunofluorescence microscopy. Results Atorvastatin treatment for 2 and 8 weeks restored BBB integrity, indicated by a substantial reduction of IgG and apo B, particularly within the hippocampus. Pravastatin, a water-soluble statin was less effective than atorvastatin (lipid-soluble). Statin effects were independent of changes in plasma lipid homeostasis. Ibuprofen, a lipid-soluble cyclooxygenase inhibitor attenuated cerebral accumulation of IgG and apo B as effectively as atorvastatin. Our findings are consistent with the drug effects being independent of plasma lipid homeostasis. Conclusion Our findings suggest that BBB dysfunction induced by chronic ingestion of SFA is reversible with timely introduction and sustained treatment with agents that suppress inflammation.
    Lipids in Health and Disease 09/2012; 11(1):117. DOI:10.1186/1476-511X-11-117 · 2.22 Impact Factor
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    • "Structural imaging with either computer tomography (CT) or T1 weighted magnetic resonance imaging (MRI) allows brain atrophy to be assessed in in vivo [3]. Different studies [3] [4] in the early stages of AD have consistently reported that, the first brain region to be affected by atrophy is the medial temporal lobe, which comprises with hippocampus proper, the para hippocampal gyrus and the amygdala. The study by Chupin et al. [5] are also consistent regarding the sources of AD. "
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    ABSTRACT: This study is to investigate the electroencephalogram (EEG) differences generated from a normal and Alzheimer's disease (AD) sources. We also investigate the effects of brain tissue distortions due to AD on EEG. We develop a realistic head model from T1 weighted magnetic resonance imaging (MRI) using finite element method (FEM) for normal source (somatosensory cortex (SC) in parietal lobe) and AD sources (right amygdala (RA) and left amygdala (LA) in medial temporal lobe). Then, we compare the AD sourced EEGs to the SC sourced EEG for studying the nature of potential changes due to sources and 5% to 20% brain tissue distortions. We find an average of 0.15 magnification errors produced by AD sourced EEGs. Different brain tissue distortion models also generate the maximum 0.07 magnification. EEGs obtained from AD sources and different brain tissue distortion levels vary scalp potentials from normal source, and the electrodes residing in parietal and temporal lobes are more sensitive than other electrodes for AD sourced EEG. Keywords—Alzheimer's disease (AD), Brain tissue distortion, Electroencephalogram, Finite element method.
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    • "Consensus among clinical experts, based on robust data, that candidate biomarkers track disease progression at various stages of disease will strengthen the case for validation. A leading candidate surrogate marker is brain atrophy rate as measured by volumetric MRI; a huge body of evidence supports a link between regional brain atrophy and progression of AD pathobiology [32-34]. "
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    ABSTRACT: The field of Alzheimer's disease therapeutic research seems poised to bring to clinic the next generation of treatments, moving beyond symptomatic benefits to modification of the underlying neurobiology of the disease. But a series of recent trials has had disappointingly negative results that raise questions about our drug development strategies. Consideration of ongoing programs demonstrates difficult pitfalls. But a clear path forward is emerging. Successful strategies will utilize newly available tools to reconsider issues of diagnosis, assessment and analysis, facilitating the study of new treatments at early stages in the disease process at which they are most likely to yield major clinical benefits.
    Alzheimer's Research and Therapy 08/2009; 1(1):2. DOI:10.1186/alzrt2 · 3.98 Impact Factor
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