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.

Visuoperception test predicts pathologic diagnosis of Alzheimer disease in corticobasal syndrome

“…CBS-AD is thought to represent a form of earlyonset AD, but, at present, no genes have been identified 11 (in our cohort, APOE e4 status did not statistically differ between groups; nonetheless, the only 2 e4 homozygotes did belong to the CBS-AD group). Insofar as CBS-AD may represent a form of early-onset AD, it is consistent that one study found greater impairment of the dorsal stream in earlyonset AD than in late-onset AD.…”

“…5,11,13 The relatively young age of the patients with CBS-AD in this cohort would likely bias our result toward the null (if increasing age were causing an undetected spatial performance decline on the dorsal stream subtests). Furthermore, age-adjusted ORs were still significant for each spatial subtest.…”

“…22 The CBS-AD group scored significantly lower on the orientation-memory subtest of the Mattis DRS-2 in primary and secondary analyses. Of note, patients with CBS-AD also perform worse on the orientationmemory subcomponent of the Addenbrooke's Cognitive Examination, 9 and a recent review of 42 CBS cases identified memory impairment as being associated with CBS-AD 11 (although the nature of this impairment was not precisely defined). It remains difficult to determine which aspect of memory may be impaired because of the inclusion of orientation in this scale.…”

Atypical Parkinsonism

“…Moreover, the different phenotypes likely represent the distribution (eg, the brain areas affected) of the underlying pathology in each of these disorders, and thus, reflect more likely a spectrum rather than well-defined phenotypes, for which strictly defined clinical criteria can be applied. 10,39,45 Investigations MRI in CBD may show asymmetric frontoparietal atrophy. 46 DATscans are abnormal in CBD, as they are in PD, PSP, and MSA.…”

Alzheimer’s Disease: A Clinical Perspective

“…CBS is an unusual clinical manifestation of various neurodegenerative pathologies, AD, FTD, corticobasal degeneration (CBD). The one related to AD presents a temporo-parietal atrophy prevalent on the left side and hypoperfusion of parietal lobe, with less involvement of pre-frontal regions compare with FTD and CBD [103].…”