Executive dysfunction in frontotemporal dementia and corticobasal syndrome

Frontotemporal dementia (FTD) is a progressive neurodegenerative disease that primarily affects the frontal and anterior temporal lobes, resulting in changes in behavior, language, and cognition.1 Corticobasal syndrome (CBS) is a disorder characterized by progressive asymmetric apraxia and rigidity with other findings of cortical (e.g., alien limb, cortical sensory loss, myoclonus) and basal ganglia (e.g., bradykinesia and increased resistance to passive movement) dysfunction.2,3 Both disorders can be associated with pathologic tau aggregation.1–5 Patients with FTD and patients with CBS often have deficits in executive function,6–9 a term that encompasses complex cognitive functions such as planning, judgment, reasoning, problem solving, organization, attention, abstraction, and mental flexibility.10 Several questions, however, remain unanswered: How do the patterns of executive dysfunction of behavioral variant FTD (bv-FTD) and CBS compare? What brain areas are associated with specific symptoms of executive dysfunction in bv-FTD and CBS? These are important questions for several reasons: executive dysfunction is a clinically important symptom in FTD11 and CBS,7 but little is known about its neurobiological basis in these disorders; and insights from patients with deficits in executive function can elucidate the neuroanatomic basis of executive function in healthy people. The distributions of atrophy observed in FTD and CBS are ideal to determine the relative contributions of regions of the frontal and parietal cortexes to executive function. A review of the brain areas involved in the performance of executive function tests is beyond the scope of this article, but in summary, while intact executive function requires more fundamental cognitive abilities in other parts of the brain (including the parietal lobe12), the prefrontal cortex, especially on the left, is prominently associated with executive functions.13 Patients with FTD had high numbers of rule violations on the Tower Test compared to patients with Alzheimer disease and healthy controls,14 and impaired performance on a sorting task associated with decreased left frontal lobe volume.15 Performance on the Twenty Questions test has been shown to be impaired in patients with prefrontal cortex lesions,16 and letter fluency is impaired in patients with left prefrontal17 lesions. Patients with FTD who had progressive disease were especially impaired on digit span and inhibition of prepotent responses.18 The Delis-Kaplan Executive Function System (D-KEFS) is a battery of nine standardized executive function tests (Trail Making, Verbal Fluency, Design Fluency, Color-Word Interference, Sorting, Twenty Questions, Word Context, Tower, and Proverb interpretation) designed to comprehensively assess higher cognitive function.19 In this study, we compared D-KEFS scores between the patients with CBS and patients with FTD and determined which areas of the brain are associated with these executive functions using voxel-based morphometry (VBM) of MRI. Based on the findings discussed above and the brain areas affected in FTD and CBS, we hypothesized that patients with FTD would show more severe executive dysfunction than the patients with CBS and that this executive dysfunction would be associated with left prefrontal atrophy in the patients with FTD and left prefrontal and parietal atrophy in the patients with CBS.