Hoy, AR;
Ly, M;
Carlsson, CM;
Okonkwo, OC;
Zetterberg, H;
Blennow, K;
Sager, MA;
... Bendlin, BB; + view all
(2017)
Microstructural white matter alterations in preclinical Alzheimer's disease detected using free water elimination diffusion tensor imaging.
PLoS ONE
, 12
(3)
, Article e0173982. 10.1371/journal.pone.0173982.
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Abstract
Brain changes associated with Alzheimer’s disease (AD) begin decades before disease diagnosis. While β-amyloid plaques and neurofibrillary tangles are defining features of AD, neuronal loss and synaptic pathology are closely related to the cognitive dysfunction. Brain imaging methods that are tuned to assess degeneration of myelinated nerve fibers in the brain (collectively called white matter) include diffusion tensor imaging (DTI) and related techniques, and are expected to shed light on disease-related loss of structural connectivity. Participants (N = 70, ages 47–76 years) from the Wisconsin Registry for Alzheimer’s Prevention study underwent DTI and hybrid diffusion imaging to determine a free-water elimination (FWE-DTI) model. The study assessed the extent to which preclinical AD pathology affects brain white matter. Preclinical AD pathology was determined using cerebrospinal fluid (CSF) biomarkers. The sample was enriched for AD risk (APOE ε4 and parental history of AD). AD pathology assessed by CSF analyses was significantly associated with altered microstructure on both DTI and FWE-DTI. Affected regions included frontal, parietal, and especially temporal white matter. The f-value derived from the FWE-DTI model appeared to be the most sensitive to the relationship between the CSF AD biomarkers and microstructural alterations in white matter. These findings suggest that white matter degeneration is an early pathological feature of AD that may have utility both for early disease detection and as outcome measures for clinical trials. More complex models of microstructural diffusion properties including FWE-DTI may provide increased sensitivity to early brain changes associated with AD over standard DTI.
| Type: | Article |
|---|---|
| Title: | Microstructural white matter alterations in preclinical Alzheimer's disease detected using free water elimination diffusion tensor imaging |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0173982 |
| Publisher version: | https://doi.org/10.1371/journal.pone.0173982 |
| Language: | English |
| Additional information: | This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. |
| Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, Mild Cognitive Impairment, Fiber Tractography, Corpus-Callosum, Healthy-Adults, CSF, Brain, Dementia, Mri, Schizophrenia, Degeneration |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1550012 |
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