Neurocognitive contributions to verbal fluency deficits in frontotemporal lobar degeneration

Abstract

Objective: To test the hypothesis that different neurocognitive networks underlie verbal fluency deficits in frontotemporal lobar degeneration (FTLD).Methods: Letter ("FAS") and semantic ("animal") fluency tests were administered to patients with a behavioral/dysexecutive disorder (bvFTLD; n ϭ 71), semantic dementia (SemD; n ϭ 21), and progressive nonfluent aphasia (PNFA; n ϭ 26). Tests measuring working memory, naming/lexical retrieval, and semantic knowledge were also obtained. MRI voxel-based morphometry (VBM) studies were obtained on a subset of these patients (bvFTLD, n ϭ 51; PNFA, n ϭ 11; SemD, n ϭ 10). Results:Patients with SemD were disproportionately impaired on the semantic fluency measure.Reduced output on this test was correlated with impaired performance on naming/lexical retrieval tests. VBM analyses related reduced letter and semantic fluency to anterior and inferior left temporal lobe atrophy. Patients with bvFTLD were equally impaired on both fluency tests. Poor performance on both fluency tests was correlated with low scores on working memory and naming/ lexical retrieval measures. In this group, MRI-VBM analyses related letter fluency to bilateral frontal atrophy and semantic fluency to left frontal/temporal atrophy. Patients with PNFA were also equally impaired on fluency tests. Reduced semantic fluency output was correlated with reduced performance on naming/lexical retrieval tests. MRI-VBM analyses related semantic fluency to the right frontal lobe and letter fluency to left temporal atrophy. Frontotemporal lobar degeneration (FTLD) is a progressive neurodegenerative illness associated with frontal and temporal lobe atrophy. Conclusions:1 Clinical subgroups of patients with FTLD include a decline in behavior, comportment, and executive functioning (bvFTLD) 2,3 ; semantic dementia (SemD) 4 associated with fluent progressive aphasia, impaired word comprehension, and poor object knowledge; and progressive nonfluent aphasia (PNFA) 5 associated with effortful speech and impaired grammatic comprehension. Imaging studies have shown that these patients have different distributions of cortical atrophy. 6Recent research has demonstrated that these FTLD subgroups can present with impaired executive control as seen by reduced performance on tests of letter ("FAS") and semantic ("animals" 7,8 ) fluency. Because autopsy-confirmed patients with FTLD produce differing patterns of impairment on letter as compared with semantic fluency tests, these tests may help differentiate between Alzheimer disease (AD) and FTLD and between FTLD subtypes. [9][10][11][12] Functional neuroimaging studies of healthy adults associate these tasks with partially distinct activation patterns.

Why are patients with progressive nonfluent aphasia nonfluent?

“…13 Moreover, overlapping left IFC and aSTC thinning for nonfluent speech and grammatic difficulty is consistent with our observation finding that difficulty producing syntactically complex structures contributes to nonfluent speech in PNFA. While prior work has related reduced category naming fluency to left frontal regions in PNFA, 15 the neuroimaging results of the present study did not reveal an overlap between areas of thinning related to nonfluent speech and areas of thinning related to category naming fluency. We are unaware of prior work directly relating speech-sound errors to cortical atrophy in PNFA, although a study of stroke patients has associated AOS with left insula stroke.…”

“…15,28 Deficits in executive functioning have been hypothesized to interfere with strategic planning and mental search in language, and therefore potentially contribute to reduced speech fluency. 9 However, our regression analyses indicated that executive functioning does not contribute to reduced WPM in PNFA.…”

“…13 Patients with PNFA also have atrophy in left insula, an area associated with motorspeech errors, 7 and in left dorsolateral prefrontal cortex, an area associated with mental search. 14,15 In this study, we related fluency, grammar, executive functioning, and speechsound production to quantitative measures of cortical thickness. We predicted that nonfluent speech would be related to limited grammatic processing in PNFA and reduced executive functioning in bvFTD.…”

Qualitative Assessment of Verbal Fluency Performance in Frontotemporal Dementia

“…Executive control is often evaluated by tests of verbal fluency [7,8]. Verbal fluency refers to the ability to generate words from a semantic category (e.g., animals, groceries, fruits) or a specified letter of the alphabet within a limited time.…”

“…Based on the differences in clinical subtypes of FTD and PPA, a disparate pattern of impairment in verbal fluency tasks is expected. Indeed, a previous study showed that patients with semantic variant PPA were more impaired on semantic than letter fluency, whereas patients with bvFTD and nonfluent/agrammatic variant PPA were equally impaired in both types of tasks [8]. …”