What matters in white matter dementia?

Abstract

Dementia studies has primarily focused on disorders of the cerebral cortex and subcortical gray matter, what originated the concepts of cortical and subcortical dementias respectively. Dementia related mainly with cerebral white matter have received less attention. We present five different cases, each one illustrative of a dementia subtype that could be assigned under the category of ‘white matter dementia’: CADASIL, progressive subcortical gliosis, progressive multifocal leucoencephalopathy, normopressure hydrocephalus and brain injury. Besides that, recent clinical and scientific literature on white matter dementia was reviewed. The composition of exuberant psychiatric symptoms and personality changes (mainly apathy, but also desinhibition) with neurological signs (pyramidal alone or associated with extrapyramidal signs, ataxia and urinary incontinence) and with specific cognitive impairment (mentioned above), should rise strongly the possibility of a white-matter dementia, instead of a cortical or subcortical form of dementia.

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).…”

White matter dementia then… and now

“…This concept thus led to the proposal of a new syndrome that departed from the conventional understanding of dementia, and our idea, form a different perspective than the powerful corticocentric bias in clinical neuroscience (6), met with only modest enthusiasm. As time and knowledge advanced, with MRI and neuropsychological testing regularly demonstrating correlations between white matter lesions and cognitive loss, the construct of WMD slowly attracted more attention (7)(8)(9)(10)(11)(12), and this issue of Frontiers in Neurology embraces the concept with a series of articles dedicated to the topic. In this introductory paper, I will offer a focused review of the original formulation of WMD, its clinical characterization, its importance in the study of connectivity and distributed neural networks, its relevance to neurodegenerative diseases, and new perspectives in treatment, prevention, and recovery.…”