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S1‐03‐04: MultiModal imaging and connectivity: What leads to what and where in Alzheimer's disease
Author(s) -
Buckner Randy L.
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.05.170
Subject(s) - default mode network , disease , neuroscience , context (archaeology) , atrophy , pathological , vulnerability (computing) , psychology , neuroimaging , medicine , functional connectivity , biology , pathology , computer science , paleontology , computer security
(23%) and incidental white matter disease (95%) in the elderly. Community autopsy studies suggest that co-morbid Cerebrovascular Disease (CVD) and AD are frequent in the elderly and the combination is likely the commonest substrate of dementia. Methods: New imaging techniques are now available for in vivo detection of AD, for example, amyloid PET imaging and direct visualization of amyloid plaques using 7 Tesla MRI. Appropriate MRI acquisition and analysis techniques are helping to elucidate complex CVD/AD relationships, including overt and covert ischemic lesions, using computer-assisted brain tissue segmentation to quantify volumes of grey, white and CSF compartments, and white matter hyperintensities. Invisible white matter changes can be further probed by Diffusion Tensor Imaging and MR Spectroscopy providing insight into microstructural integrity and metabolite profiles. By co-registrating neuropathology with post-mortem MRI, the clinico-pathophysiology of white matter hyperintensities can be further interrogated. Results: Such studies suggest that infarction (i.e. necrosis) usually arises from arterial/arteriolar disease. The incidental hyperintensitites, however, likely arise from a different ischemic mechanism. Specifically, confluent periventricular hyperintensities may relate to veno-occlusive disease, from venous collagenosis, reflecting chronic hypoperfusion of periventricular white matter. Periventricular venular occlusions gradually multiply, driven by aging and vascular risk factors, causing widespread, patchy confluent periventricular hyperintensities, likely due to blood brain barrier leakage and vasogenic edema, and possibly ependymal CSF leakage, which together degrade white matter slowly through apoptotic pathways. These two primary mechanisms, arteriolar infarcts and venous insufficiency, may differentially impact on cognition, gait and behaviour. Strategic lesion location, such as in the anterior dorsomedial thalamus or in the cholinergic fibre radiations, as well as lesion volume, also must be taken into account when investigating brain-behaviour relations. Conclusions: Better understanding of different etiologies of white matter disease may help determine new targets for intervention to combat this ubiquitous phenomenon of brain aging and dementia.