We investigated the cognitive and neural bases of impaired speech fluency, a central feature of primary progressive aphasia. Speech fluency was assessed in 35 patients with frontotemporal lobar degeneration (FTLD) who presented with progressive non-fluent aphasia (PNFA, n=11), semantic dementia (SemD, n=12), or a social and executive disorder without aphasia (SOC/EXEC, n=12). Fluency was quantified as the number of words per minute in an extended, semi-structured speech sample. This was related to language characteristics of the speech sample and to neuropsychological measures. PNFA patients were significantly less fluent than controls and other FTLD patients. Fluency correlated with grammatical expression but not with speech errors or executive difficulty. SemD and SOC/EXEC patients were also less fluent than controls. In SemD, fluency was associated with semantically limited content. In SOC/EXEC, fluency was associated with executive limitations. Voxel-based morphometry analyses of high-resolution MRI related fluency to gray matter volume in left inferior frontal, insula, and superior temporal regions for the entire cohort of FTLD patients. This region overlapped partially distinct atrophic areas in each FTLD subgroup. It thus appears to play a crucial role in speech fluency, which can be interrupted in different ways in different FTLD subgroups.

Objective: To investigate the cognitive and neural basis for nonfluent speech in progressive nonfluent aphasia (PNFA).Background: Nonfluent speech is the hallmark feature of PNFA, and this has been attributed to

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.

The nature and frequency of speech production errors in neurodegenerative disease have not previously been precisely quantified. In the present study, 16 patients with a progressive form of nonfluent aphasia (PNFA) were asked to tell a story from a wordless children's picture book. Errors in production were classified as either phonemic, involving language-based deformations that nevertheless result in possible sequences of English speech segments; or phonetic, involving a motor planning deficit and resulting in non-English speech segments. The distribution of cortical atrophy as revealed by structural MRI scans was examined quantitatively in a subset of PNFA patients (N=7). The few errors made by healthy seniors were only phonemic in type. PNFA patients made more than four times as many errors as controls. This included both phonemic and phonetic errors, with a preponderance of errors (82%) classified as phonemic. The majority of phonemic errors were substitutions that shared most distinctive features with the target phoneme. The systematic nature of these substitutions is not consistent with a motor planning deficit. Cortical atrophy was found in prefrontal regions bilaterally and peri-Sylvian regions of the left hemisphere. We conclude that the speech errors produced by PNFA patients are mainly errors at the phonemic level of language processing and are not caused by a motor planning impairment.

Few studies have examined connected speech in demented and non-demented patients with Parkinson’s disease (PD). We assessed the speech production of 35 patients with Lewy body spectrum disorder (LBSD), including non-demented PD patients, patients with PD dementia (PDD), and patients with dementia with Lewy bodies (DLB), in a semi-structured narrative speech sample in order to characterize impairments of speech fluency and to determine the factors contributing to reduced speech fluency in these patients. Both demented and non-demented PD patients exhibited reduced speech fluency, characterized by reduced overall speech rate and long pauses between sentences. Reduced speech rate in LBSD correlated with measures of between-utterance pauses, executive functioning, and grammatical comprehension. Regression analyses related non-fluent speech, grammatical difficulty, and executive difficulty to atrophy in frontal brain regions. These findings indicate that multiple factors contribute to slowed speech in LBSD, and this is mediated in part by disease in frontal brain regions.