White Matter Dementia: Origin, Development, Progress, and Prospects

Abstract

The term white matter dementia (WMD) was introduced in 1988 to highlight the role of white matter in the development of dementia. As the concept has been refined with new insights into the structure and function of normal and abnormal white matter, research has expanded to consider normal cognition, network connectivity, novel treatment ideas, and the etiopathogenesis of neurodegenerative dementia. Emerging data are also identifying new opportunities for dementia prevention by avoidance of acquired vascular and traumatic white matter insults. The idea of WMD promises to continue as a useful construct informing the study of dementia and the understanding of brain-behavior relationships.

Elevated plasma neurofilament light in aging reflects brain white‐matter alterations but does not predict cognitive decline or Alzheimer's disease

“…High levels of NFL were related to brain white‐matter integrity, in particular in the splenium of the corpus callosum, but did not relate to cognitive decline or upcoming AD. Future studies should test whether NFL is a stronger biomarker for other forms of dementia than AD, such as white‐matter dementia 30 …”

White Matter, Behavioral Neurology, and the Influence of Corticocentrism

“…Meanwhile, the idea of a behavioral neurology of white matter began to take shape as a complement to the study of higher cortical functions (Filley, 1998, 2001, 2021b; Filley and Fields, 2016). Allied with this notion is the concept of white matter dementia (Filley et al, 1988), which has received growing support (Caixeta, 2007; Derix, 1994; Filley et al, 2015; Goldberg and Ransom, 2003; Grigsby et al, 2014; Liu et al, 2017; Matute and Ransom, 2012; Schäfer et al, 2021; Schmahmann et al, 2008). Neurobehavioral syndromes including dementia are becoming better appreciated in association with a wide range of white matter pathologies, including genetic, demyelinative, infectious, inflammatory, vascular, toxic, metabolic, traumatic, neoplastic, and hydrocephalic disorders, and even neurodegenerative diseases have been observed to have important white matter correlates (Filley, 2021b; Filley and Fields, 2016: Filley et al, 2015).…”

Editorial: White matter dementia: neuropathological and neuropsychological underpinnings and state of the art diagnosis methods and treatments

“…Whereas, a primary focus on cortical cell bodies, dendrites, and synapses has proven enormously successful, a corticocentric approach neglects the contributions of subcortical regions ( 1 ), and white matter is easily the most prominent subcortical structure. In this context, a dementia syndrome arising from selective white matter pathology was proposed in 1988 ( 2 ), based primarily on study of toluene abuse demonstrating striking white matter toxicity that produced dementia ( 3 ). Over the ensuing years, the idea of white matter dementia steadily gained credibility as transdiagnostic synthesis of many disorders disclosed numerous commonalities implicating a critical role of white matter connectivity in human behavior and its disorders.…”