TY - JOUR
T1 - White matter hyperintensities and normal-appearing white matter integrity in the aging brain
AU - Muñoz Maniega, Susana
AU - Hernandez, Maria C. Valdes
AU - Clayden, Jonathan D.
AU - Royle, Natalie A
AU - Murray, Catherine
AU - Morris, Zoe
AU - Aribisala, Benjamin S
AU - Gow, Alan J.
AU - Starr, John M
AU - Bastin, Mark E
AU - Deary, Ian J
AU - Wardlaw, Joanna M
N1 - "The work has made use of the resources provided by the Edinburgh
Compute and Data Facility (ECDF) (http://www.ecdf.ed.ac.uk). This
work was supported by a Research into Ageing Programme grant
(to Ian J. Deary and John M. Starr) and the Age UK funded
Disconnected Mind Project (http://www.disconnectedmind.ed.ac.
uk; to Ian J. Deary, John M. Starr, and Joanna M. Wardlaw) with
additional funding from the Medical Research Council (grant
number G0701120 to Ian J. Deary, John M. Starr, Joanna M. Wardlaw,
and Mark E. Bastin). Joanna M. Wardlaw is supported by the
Scottish Funding Council through the SINAPSE Collaboration
(http://www.sinapse.ac.uk). Maria C. Valdés Hernández is funded
by The Row Fogo Charitable Trust. CCACE (G0700704/84698) is
funded by the Biotechnology and Biological Sciences Research
Council, Engineering and Physical Sciences Research Council,
Economic and Social Research Council, and the Medical Research
Council."
PY - 2015/2
Y1 - 2015/2
N2 - White matter hyperintensities (WMH) of presumed vascular origin are a common finding in brain magnetic resonance imaging of older individuals and contribute to cognitive and functional decline. It is unknown how WMH form, although white matter degeneration is characterized pathologically by demyelination, axonal loss, and rarefaction, often attributed to ischemia. Changes within normal-appearing white matter (NAWM) in subjects with WMH have also been reported but have not yet been fully characterized. Here, we describe the in vivo imaging signatures of both NAWM and WMH in a large group of community-dwelling older people of similar age using biomarkers derived from magnetic resonance imaging that collectively reflect white matter integrity, myelination, and brain water content. Fractional anisotropy (FA) and magnetization transfer ratio (MTR) were significantly lower, whereas mean diffusivity (MD) and longitudinal relaxation time (T1) were significantly higher, in WMH than NAWM (p <0.0001), with MD providing the largest difference between NAWM and WMH. Receiver operating characteristic analysis on each biomarker showed that MD differentiated best between NAWM and WMH, identifying 94.6% of the lesions using a threshold of 0.747 x 10(-9) m(2)s(-1) (area under curve, 0.982; 95% CI, 0.975-0.989). Furthermore, the level of deterioration of NAWM was strongly associated with the severity of WMH, with MD and T1 increasing and FA and MTR decreasing in NAWM with increasing WMH score, a relationship that was sustained regardless of distance from the WMH. These multimodal imaging data indicate that WMH have reduced structural integrity compared with surrounding NAWM, and MD provides the best discriminator between the 2 tissue classes even within the mild range of WMH severity, whereas FA, MTR, and T1 only start reflecting significant changes in tissue microstructure as WMH become more severe. (C) 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).
AB - White matter hyperintensities (WMH) of presumed vascular origin are a common finding in brain magnetic resonance imaging of older individuals and contribute to cognitive and functional decline. It is unknown how WMH form, although white matter degeneration is characterized pathologically by demyelination, axonal loss, and rarefaction, often attributed to ischemia. Changes within normal-appearing white matter (NAWM) in subjects with WMH have also been reported but have not yet been fully characterized. Here, we describe the in vivo imaging signatures of both NAWM and WMH in a large group of community-dwelling older people of similar age using biomarkers derived from magnetic resonance imaging that collectively reflect white matter integrity, myelination, and brain water content. Fractional anisotropy (FA) and magnetization transfer ratio (MTR) were significantly lower, whereas mean diffusivity (MD) and longitudinal relaxation time (T1) were significantly higher, in WMH than NAWM (p <0.0001), with MD providing the largest difference between NAWM and WMH. Receiver operating characteristic analysis on each biomarker showed that MD differentiated best between NAWM and WMH, identifying 94.6% of the lesions using a threshold of 0.747 x 10(-9) m(2)s(-1) (area under curve, 0.982; 95% CI, 0.975-0.989). Furthermore, the level of deterioration of NAWM was strongly associated with the severity of WMH, with MD and T1 increasing and FA and MTR decreasing in NAWM with increasing WMH score, a relationship that was sustained regardless of distance from the WMH. These multimodal imaging data indicate that WMH have reduced structural integrity compared with surrounding NAWM, and MD provides the best discriminator between the 2 tissue classes even within the mild range of WMH severity, whereas FA, MTR, and T1 only start reflecting significant changes in tissue microstructure as WMH become more severe. (C) 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).
KW - Aging
KW - White matter hyperintensities
KW - Normal-appearing white matter
KW - Multimodal MRI
KW - SMALL VESSEL DISEASE
KW - DIFFUSION TENSOR
KW - OLD-AGE
KW - LEUKOARAIOSIS
KW - ABNORMALITIES
KW - COGNITION
KW - IMAGES
U2 - 10.1016/j.neurobiolaging.2014.07.048
DO - 10.1016/j.neurobiolaging.2014.07.048
M3 - Article
C2 - 25457555
SN - 0197-4580
VL - 36
SP - 909
EP - 918
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 2
ER -