Regional staging of white matter signal abnormalities in aging and Alzheimer's disease.
White matter lesions, quantified as 'white matter signal abnormalities' (WMSA) on neuroimaging, are common incidental findings on brain images of older adults. This tissue damage is linked to cerebrovascular dysfunction and is associated with cognitive decline. The regional distribution of WMSA throughout the cerebral white matter has been described at a gross scale; however, to date no prior study has described regional patterns relative to cortical gyral landmarks which may be important for understanding functional impact. Additionally, no prior study has described how regional WMSA volume scales with total global WMSA. Such information could be used in the creation of a pathologic 'staging' of WMSA through a detailed regional characterization at the individual level. Magnetic resonance imaging data from 97 cognitively-healthy older individuals (OC) aged 52-90 from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study were processed using a novel WMSA labeling procedure described in our prior work. WMSA were quantified regionally using a procedure that segments the cerebral white matter into 35 bilateral units based on proximity to landmarks in the cerebral cortex. An initial staging was performed by quantifying the regional WMSA volume in four groups based on quartiles of total WMSA volume (quartiles I-IV). A consistent spatial pattern of WMSA accumulation was observed with increasing quartile. A clustering procedure was then used to distinguish regions based on patterns of scaling of regional WMSA to global WMSA. Three patterns were extracted that showed high, medium, and non-scaling with global WMSA. Regions in the high-scaling cluster included periventricular, caudal and rostral middle frontal, inferior and superior parietal, supramarginal, and precuneus white matter. A data-driven staging procedure was then created based on patterns of WMSA scaling and specific regional cut-off values from the quartile analyses. Individuals with Alzheimer's disease (AD) and mild cognitive impairment (MCI) were then additionally staged, and significant differences in the percent of each diagnostic group in Stages I and IV were observed, with more AD individuals residing in Stage IV and more OC and MCI individuals residing in Stage I. These data demonstrate a consistent regional scaling relationship between global and regional WMSA that can be used to classify individuals into one of four stages of white matter disease. White matter staging could play an important role in a better understanding and the treatment of cerebrovascular contributions to brain aging and dementia.
Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA; Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Emily R
ER
Lindemer
Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA; Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Douglas N
DN
Greve
Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA; Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Computer Science and Artificial Intelligence Laboratory (CSAIL), Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
Bruce R
BR
Fischl
Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA; Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Jean C
JC
Augustinack
Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA; Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Neuroimaging Research for Veterans (NeRVe) Center, VA Boston Healthcare System, Boston, MA, USA.
David H
DH
Salat
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000150:complications* / Q000000981:diagnostic imaging; D000704:Analysis of Variance; D001931:Brain Mapping; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D056784:Leukoencephalopathies / Q000000981:diagnostic imaging* / Q000209:etiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales
Aging; Alzheimer's disease; Cerebrovascular; Staging; White matter