AUTHOR=Filley Christopher M. 

TITLE=White matter dementia then… and now

JOURNAL=Frontiers in Neurology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.1043583

DOI=10.3389/fneur.2022.1043583

ISSN=1664-2295

ABSTRACT=White matter dementia (WMD) is a concept introduced in 1988 to highlight the importance of white matter pathology in producing cognitive dysfunction and dementia. Whereas gray matter, particularly the cerebral cortex, has been primarily investigated in the dementias, subcortical pathology has long been correlated with cognitive loss, and a corticocentric perspective cannot account for the full range of neurobehavioral disorders. Within the subcortical regions, white matter is prominent, accounting for about half the volume of the adult brain, and many white matter diseases, injuries, and intoxications can produce cognitive dysfunction so severe as to justify the term dementia. Recognition of this novel syndrome relied heavily on the introduction of magnetic resonance imaging (MRI) in the early 1980s that permitted in vivo visualization of white matter lesions. Neuropsychological studies clarified the clinical presentation of WMD by identifying a distinct profile dominated by cognitive slowing and executive dysfunction, and a precursor syndrome of mild cognitive dysfunction was proposed to identify early cognitive impairment that may later evolve to WMD. As knowledge advanced, the role of white matter in structural connectivity within distributed neural networks was elucidated. In addition, white matter pathology was associated with neurodegenerative diseases such as Alzheimer’s Disease and chronic traumatic encephalopathy, with potentially transformative clinical implications. In particular, preventive measures and treatments exploiting white matter restoration and plasticity are gaining much attention. Today, WMD has matured into an increasingly relevant concept, integrating knowledge from across the spectrum of clinical neuroscience, informing new investigations into many disorders that require better understanding, and enabling a more complete understanding of brain-behavior relationships.