Abstract
White matter dementia (WMD) is a syndrome highlighting white matter pathology in cognitive dysfunction and dementia. Whereas investigation of dementia has primarily focused on gray matter, particularly the cerebral cortex, a corticocentric perspective can be limiting. White matter occupies half the brain volume, and transdiagnostic study shows that many white matter disorders produce cognitive dysfunction sufficient to justify the term dementia. Toluene leukoencephalopathy was the first and most compelling example of WMD, in which cognitive slowing and executive dysfunction are prominent, and a precursor syndrome of mild cognitive dysfunction has been proposed. Neuroscience has come to recognize the central role of white matter in structural connectivity, and white matter pathology is relevant to Alzheimer's Disease and chronic traumatic encephalopathy. Treatment and prevention exploiting white matter restoration and plasticity may be transformative. Since its introduction, WMD has matured as a syndrome advancing the understanding of brain-behavior relationships.
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