Document Detail

Brain structural and functional connectivity and the progression of neuropathology in Alzheimer's disease.
MedLine Citation:
PMID:  22669012     Owner:  NLM     Status:  MEDLINE    
In our contribution to this special issue focusing on advances in Alzheimer's disease (AD) research since the centennial, we will briefly review some of our own studies applying magnetic resonance imaging (MRI) measures of function and connectivity for characterization of genetic contributions to the neuropathology of AD and as candidate biomarkers. We review how functional MRI during both memory encoding and at rest is able to define APOE4 genotype-dependent physiological changes decades before potential development of AD and demonstrate changes distinct from those with healthy aging. More generally, imaging provides a powerful quantitative measure of phenotype for understanding associations arising from whole genome studies in AD. Structural connectivity measures derived from diffusion tensor MRI (DTI) methods offer additional markers of neuropathology arising from the secondary changes in axonal caliber and myelination that accompany decreased neuronal activity and neurodegeneration. We illustrate applications of DTI for more finely mapping neurodegenerative changes with AD in the thalamus in vivo and for defining neuropathological changes in the white matter itself. The latter efforts have highlighted how sensitivity to the neuropathology can be enhanced by using more specific DTI measures and interpreting them relative to knowledge of local white matter anatomy in the healthy brain. Together, our studies and related work are helping to establish the exciting potential of a new range of MRI methods as neuropathological measures and as biomarkers of disease progression.
Paul M Matthews; Nicola Filippini; Gwenaëlle Douaud
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Journal of Alzheimer's disease : JAD     Volume:  33 Suppl 1     ISSN:  1875-8908     ISO Abbreviation:  J. Alzheimers Dis.     Publication Date:  2013  
Date Detail:
Created Date:  2012-12-28     Completed Date:  2013-06-06     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  9814863     Medline TA:  J Alzheimers Dis     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  S163-72     Citation Subset:  IM    
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MeSH Terms
Alzheimer Disease / pathology*,  physiopathology
Brain / pathology*,  physiopathology
Diffusion Tensor Imaging
Disease Progression
Magnetic Resonance Imaging
Nerve Net / pathology*,  physiopathology
Neurons / pathology*
Grant Support
G9409531//Medical Research Council; //Medical Research Council

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