The corticobasal syndrome-Alzheimer's disease conundrum

Abstract

Corticobasal syndrome (CBS), once thought to be pathognomonic for corticobasal degeneration pathology, is increasingly reported with various underlying pathologies. Alzheimer's disease is one such pathology, also once believed to be unique for its clinical syndrome of dementia of the Alzheimer's type. CBS is believed to result from topography of asymmetric parietofrontal cortical lesion involvement, rather than lesion subtype. However, this topographical pattern is strikingly different to that typically associated with AD for unclear reasons. This article will focus on CBS with underlying AD pathology (CBS-AD), and will review associated clinical, imaging and demographic factors. Predicting AD pathology is of marked interest as disease-modifying therapies loom on the horizon, with biomarkers and imaging research underway. By reviewing the literature for CBS-AD case reports and series and contrasting them with CBS with underlying corticobasal degeneration pathology cases, the article aims to examine factors that may predict AD pathology. How AD pathology may produce this clinical phenotype, rather than the prototype dementia of the Alzheimer's type, will also be reviewed.

Figure 1. Voxel-based morphometry results showing patterns of gray matter loss in six subjects with corticobasal syndrome with corticobasal degeneration and five subjects with corticobasal syndrome with Alzheimer’s disease compared with 20 age- and gender-matched controls

The CBS-AD subjects were more highly educated and younger than the CBS-CBD subjects. Age and gender were included as covariates in the model. Results are shown on transparent renders of the brain at a statistical threshold of p < 0.001 uncorrected for multiple comparisons. AD: Alzheimer’s disease; CBD: Corticobasal degeneration; CBS: Corticobasal syndrome; L: Left; R: Right.