Subcortical Gliosis and Leukodystrophy Overlap Syndromes as a Cause of Late-onset Dementia

Review Article

Submission date: 5th August 2009, Acceptance date: 24th August 2009

ABSTRACT

Neuroimaging is a routine part of the dementia syndrome evaluation. It frequently reveals perturbed white matter integrity. These perturbations, commonly referred to as leukoaraiosis or white matter disease, are often attributed to microvascular ischemia. When present, clinicians must decide whether white matter changes relate etiologically to clinical cognitive decline. We recently described a large autosomal dominant kindred in which multiple affected members were diagnosed initially with vascular dementia due to subcortical microischemic white matter disease. Subsequent  brain autopsies revealed subcortical gliosis, features suggestive of late-onset leukodystrophy, and a lack of microvascular ischemic disease. This review emphasizes that what is radiographically classified as microischemic white matter disease is not necessarily due to ischemia, and discusses the emerging realization that subcortical gliosis–leukodystrophy overlap syndromes can cause late-life dementia.

Keywords: dementia, frontotemporal dementia, hereditary leukodystrophy with axonal spheroids, leukoaraiosis, leukodystrophy, subcortical gliosis, white matter disease

Correspondence: Russell H Swerdlow, Landon Center on Aging, MS 2012, 3901 Rainbow Blvd, Kansas City, KS 66160, USA. Tel: +1-912-588-6970; fax: +1-913-588-0681; e-mail: rswerdlow@kumc.edu