Spontaneous speech of healthy adults consists of alternating periods of fluent and hesitant segments, forming temporal cycles in speech fluency. The regularity of these cycles may be related to the functioning of brain networks during speech planning and execution. This paper investigates the theoretical link between human cognitive functioning and temporal cycles in speech production using a quantitative time series analysis to characterize the regularity and frequency of temporal cycles in adults with differing levels and etiology of cognitive decline. We compare spontaneous speech of adults without a neurological diagnosis, both older and younger, to that of adults with frontotemporal lobar degeneration (FTLD). Two measures of temporal cycle frequency (mean and mode) calculated from the power spectrum of speech fluency represented as a time series were found to be associated with subjects’ age, regardless of diagnosis of dementia. Two measures of periodicity (g-statistic and rhythmicity-index), as well as mean frequency, differentiated between adults with and without dementia. Our study confirms the presence of regular temporal cycles in spontaneous speech and suggests that temporal cycle characteristics are affected in different ways by declines in cognitive functioning due to dementia and aging.
from the Journal of Neurolinguistics
Over a 100 years have passed since Pick’s description of what is now termed frontotemporal lobar degeneration (FTLD). FTLD is a topic of intense current research interest yet some relevant contributions by non-English speaking authors have received little attention, which makes the history of FTLD research incomplete. In the hopes of filling some of the gaps in the history of FTLD research, the present article introduces fundamental work carried out in Argentina during the first half of the 20th century by Christfried Jakob and Braulio A. Moyano. Jakob’s neurophilosophy, as well as his empirical descriptions on dementia and theoretic insights into the role of the frontal lobes are highlighted. Moyano’s works on frontotemporal dementia (FTD), specifically concerning language deficits and the concept of focal pathology in Alzheimer disease presenting with progressive aphasia are introduced. These early contributions are examined in the light of the current knowledge on FTLD, highlighting some of the authors’ early original contributions, as well as their misconceptions. These authors remain largely unknown despite the fact that their contributions were fundamental in kindling interest in behavioral neurology in Latin America, which continues to this day.
The FOXP2 gene is mutated in a severe monogenic form of speech and language deficits, but no study on the influence of genetic variations within FOXP2 in neurological disorders characterized by language impairment is available yet. In the present study, we investigated the impact of common FOXP2 polymorphisms with regard to frontotemporal lobar degeneration (FTLD). Two-hundred ten FTLD patients underwent clinical and a wide standardized neuropsychological examination as well as brain imaging study. In all patients, and in 200 age-matched healthy controls, four FOXP2 polymorphisms were evaluated, namely rs2396753, rs1456031, rs17137124 and rs1852469. SPECT images were analyzed by Statistical Parametric Mapping (SPM5). No significant differences of the four FOXP2 polymorphisms in genotype distribution and allele frequency between FTLD and controls were observed. A significant and specific association between rs1456031 TT and rs17137124 TT genotypes and verbal fluency scores was reported. The two polymorphisms showed an addictive effect. When the analysis was computed on the number of observations over time, and 391 assessments considered, comparable results were obtained. FTLD patients carrying at-risk polymorphisms showed greater hypoperfusion in the frontal areas, namely the left inferior frontal gyrus, and putamen, compared to the non-carriers (p < 0.005). Genetic variations within FOXP2 do not represent a genetic risk to FTLD per se, but modulate FTLD presentation when disease is overt, affecting language performances and leading to hypoperfusion in language-associated brain areas.
from the Journal of Alzheimer’s Disease
Primary progressive aphasia (PPA) is a neurodegenerative disorder with language impairment as the primary feature. Different subtypes have been described and the 3 best characterized are progressive nonfluent aphasia (PNFA), semantic dementia (SD) and logopenic/phonological aphasia (LPA). Of these subtypes, LPA is most commonly associated with Alzheimer’s disease (AD) pathology. However, the features of PPA associated with AD have not been fully defined. Here we retrospectively identified 14 patients with PPA and either pathologically confirmed AD or cerebrospinal fluid (CSF) biomarkers consistent with AD. Analysis of neurological and neuropsychological features revealed that all patients had a syndrome of LPA with relatively nonfluent spontaneous speech, phonemic errors, and reduced digit span; most patients also had impaired verbal episodic memory. Analysis of the pattern of cortical thinning in these patients revealed left posterior superior temporal, inferior parietal, medial temporal, and posterior cingulate involvement and in patients with more severe disease, increasing involvement of left anterior temporal and frontal cortices and right hemisphere areas in the temporo-parietal junction, posterior cingulate, and medial temporal lobe. We propose that LPA may be a “unihemispheric” presentation of AD, and discuss this concept in relation to accumulating evidence concerning language dysfunction in AD.
Primary progressive aphasia (PPA) is a group of disorders with progressive language impairment. Abnormal behaviour may develop in PPA as the disease evolves, but the clinical features and brain basis of behavioural change in PPA have not been fully defined. 33 PPA patients (9 semantic dementia, SD, 14 progressive nonfluent aphasia, PNFA, 7 logopenic/phonological aphasia, LPA and 3 patients with a PPA syndrome in association with progranulin mutations, GRN-PPA) were assessed using the Neuropsychiatric Inventory to record behavioural changes, as well as volumetric MR imaging. The most common abnormal behaviours in SD were irritability, disinhibition, depression and abnormal appetite, in PNFA apathy, agitation and depression, in LPA anxiety, irritability, agitation and apathy, and in GRN-PPA apathy and irritability. Voxel-based morphometry analysis revealed greater atrophy of right lateral orbitofrontal cortex (OFC) in PPA patients with anxiety, apathy, irritability/lability and abnormal appetite/eating disorders, and greater atrophy of left OFC in those with disinhibition. Areas involved beyond OFC included right dorsolateral prefrontal cortex (apathy), right cingulate (irritability/lability) and left anterior superior and medial temporal lobe (disinhibition). Behavioural abnormalities may be clinically significant in PPA, and these abnormalities are underpinned by atrophy of overlapping frontotemporal networks centred on OFC.
from the Journal of the Neurological Sciences
Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disorder that affects language. We applied a computerized information-theoretic technique to assess the type and severity of language-related FTLD symptoms. Audio-recorded samples of 48 FTLD patients from three participating medical centers were elicited using the Cookie-Theft picture stimulus. The audio was transcribed and analyzed by calculating two measures: a perplexity index and an out-of-vocabulary (OOV) rate. The perplexity index represents the degree of deviation in word patterns used by FTLD patients compared to patterns of healthy adults. The OOV rate represents the proportion of words used by FTLD patients that were not used by the healthy speakers to describe the stimulus. In this clinically well-characterized cohort, the perplexity index and the OOV rate were sensitive to spontaneous language manifestations of semantic dementia and the distinction between semantic dementia and progressive logopenic aphasia variants of FTLD. Our study not only supports a novel technique for the characterization of language-related symptoms of FTLD in clinical trial settings, it also validates the basis for the clinical diagnosis of semantic dementia as a distinct syndrome.
from the Journal of Neurolinguistics
The FTLD-modified Clinical Dementia Rating scale is a reliable tool for defining disease severity in Frontotemporal Lobar Degeneration: evidence from a brain SPECT study
Conclusions: The recently introduced FTLD-modified CDR scale correlates with the degree of frontotemporal hypoperfusion in patients with FTLD. This study confirms and further supports the usefulness of FTLD-modified CDR in future clinical trials to monitor disease progression.
from the European Journal of Neurology
The clinical and neuroanatomical correlates of specific apraxias in neurodegenerative disease are not well understood. Here we addressed this issue in progressive nonfluent aphasia (PNFA), a canonical subtype of frontotemporal lobar degeneration that has been consistently associated with apraxia of speech (AOS) and in some cases orofacial apraxia, limb apraxia and/or parkinsonism. Sixteen patients with PNFA according to current consensus criteria were studied. Three patients had a corticobasal syndrome (CBS) and two a progressive supranuclear palsy (PSP) syndrome. Speech, orofacial and limb praxis functions were assessed using the Apraxia Battery for Adults-2 and a voxel-based morphometry (VBM) analysis was conducted on brain MRI scans from the patient cohort in order to identify neuroanatomical correlates. All patients had AOS based on reduced diadochokinetic rate, 69% of cases had an abnormal orofacial apraxia score and 44% of cases (including the three CBS cases and one case with PSP) had an abnormal limb apraxia score. Severity of orofacial apraxia (but not AOS or limb apraxia) correlated with estimated clinical disease duration. The VBM analysis identified distinct neuroanatomical bases for each form of apraxia: the severity of AOS correlated with left posterior inferior frontal lobe atrophy; orofacial apraxia with left middle frontal, premotor and supplementary motor cortical atrophy; and limb apraxia with left inferior parietal lobe atrophy. Our findings show that apraxia of various kinds can be a clinical issue in PNFA and demonstrate that specific apraxias are clinically and anatomically dissociable within this population of patients.
from the Journal of Neurology
from the Journal of Neurology
The semantic variant of primary progressive aphasia (PPA) is characterized by the combination of word comprehension deficits, fluent aphasia and a particularly severe anomia. In this study, two novel tasks were used to explore the factors contributing to the anomia. The single most common factor was a blurring of distinctions among members of a semantic category, leading to errors of overgeneralization in word–object matching tasks as well as in word definitions and object descriptions. This factor was more pronounced for natural kinds than artifacts. In patients with the more severe anomias, conceptual maps were more extensively disrupted so that inter-category distinctions were as impaired as intra-category distinctions. Many objects that could not be named aloud could be matched to the correct word in patients with mild but not severe anomia, reflecting a gradual intensification of the semantic factor as the naming disorder becomes more severe. Accurate object descriptions were more frequent than accurate word definitions and all patients experienced prominent word comprehension deficits that interfered with everyday activities but no consequential impairment of object usage or face recognition. Magnetic resonance imaging revealed three characteristics: greater atrophy of the left hemisphere; atrophy of anterior components of the perisylvian language network in the superior and middle temporal gyri; and atrophy of anterior components of the face and object recognition network in the inferior and medial temporal lobes.
from the Journal of Neurology
Few studies have assessed whether the patterns of neuropsychological impairment in patients with different frontotemporal lobar degeneration (FTLD) subtypes remain distinct over the duration of their illness or devolve into a common, undifferentiated neuropsychological state. A longitudinal neuropsychological analysis was obtained over 100 months assessing executive control, language/naming, and visuoconstruction in 441 patients diagnosed with Alzheimer’s disease (AD) and four FTLD subtypes, i.e., a social comportment/dysexecutive (SOC/EXEC) disorder; progressive non-fluent aphasia (PNFA); semantic dementia (SemD); and corticobasal degeneration (CBD). Initial group differences on each measure were maintained over the duration of illness, including several double dissociations. For example, AD patients exhibited a decline in ‘animal’ fluency; PNFA patients had difficulty on tests of executive control, SemD maintained their impairment on tests of naming, and CBD had presented with performance on visuoconstructional tests. None of the group by neuropsychological task interactions evaluating longitudinal decline was significant, suggesting that performance does not converge onto a common subtype over time. These data indicate that distinct patterns of neuropsychological impairment are maintained longitudinally, reflecting the unique anatomic distribution of relative disease burden in AD and FTLD. (PsycINFO Database Record (c) 2009 APA, all rights reserved)
Neuropathological Investigation of Regions Responsible for Semantic Aphasia in Frontotemporal Lobar Degeneration
Background/Aims: Semantic dementia is a subtype of frontotemporal lobar degeneration, of which an initial symptom is semantic aphasia. Semantic dementia pathologically corresponds to atypical Pick’s disease (aPiD), showing ubiq- uitin-positive inclusions similar to those in dementia with motor neuron disease (D-MND). Previous studies have not clarified the regions responsible for semantic aphasia in aPiD, and there have been no reported neuropathological studies concerning its pathomechanism. Methods: We neuropathologically investigated aPiD and D-MND cases with and without semantic aphasia. Results: We determined that the regions involved in the early stage of the disease course of semantic dementia were more restricted to the anterior and inferior portion of the temporal lobe on the side of the dominant hemisphere. Conclusion: Degeneration of the temporal pole is most likely to participate in the pathomechanism of SA in semantic dementia.