Neurocognitive basis of repetition deficits in primary progressive aphasia.
Ontology highlight
ABSTRACT:
SUBMITTER: Lukic S
PROVIDER: S-EPMC6669076 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
Publications
Neurocognitive basis of repetition deficits in primary progressive aphasia.
Lukic Sladjana S Mandelli Maria Luisa ML Welch Ariane A Jordan Kesshi K Shwe Wendy W Neuhaus John J Miller Zachary Z Hubbard H Isabel HI Henry Maya M Miller Bruce L BL Dronkers Nina F NF Gorno-Tempini Maria Luisa ML
Brain and language 20190502
Previous studies indicate that repetition is affected in primary progressive aphasia (PPA), particularly in the logopenic variant, due to limited auditory-verbal short-term memory (avSTM). We tested repetition of phrases varied by length (short, long) and meaning (meaningful, non-meaningful) in 58 participants (22 logopenic, 19 nonfluent, and 17 semantic variants) and 21 healthy controls using a modified Bayles repetition test. We evaluated the relation between cortical thickness and repetition ...[more]
Similar Datasets
Project description:The extent to which non-linguistic auditory processing deficits may contribute to the phenomenology of primary progressive aphasia is not established. Using non-linguistic stimuli devoid of meaning we assessed three key domains of auditory processing (pitch, timing and timbre) in a consecutive series of 18 patients with primary progressive aphasia (eight with semantic variant, six with non-fluent/agrammatic variant, and four with logopenic variant), as well as 28 age-matched healthy controls. We further examined whether performance on the psychoacoustic tasks in the three domains related to the patients' speech and language and neuropsychological profile. At the group level, patients were significantly impaired in the three domains. Patients had the most marked deficits within the rhythm domain for the processing of short sequences of up to seven tones. Patients with the non-fluent variant showed the most pronounced deficits at the group and the individual level. A subset of patients with the semantic variant were also impaired, though less severely. The patients with the logopenic variant did not show any significant impairments. Significant deficits in the non-fluent and the semantic variant remained after partialling out effects of executive dysfunction. Performance on a subset of the psychoacoustic tests correlated with conventional verbal repetition tests. In sum, a core central auditory impairment exists in primary progressive aphasia for non-linguistic stimuli. While the non-fluent variant is clinically characterized by a motor speech deficit (output problem), perceptual processing of tone sequences is clearly deficient. This may indicate the co-occurrence in the non-fluent variant of a deficit in working memory for auditory objects. Parsimoniously we propose that auditory timing pathways are altered, which are used in common for processing acoustic sequence structure in both speech output and acoustic input.
| S-EPMC4892752 | biostudies-literature
Project description:Aphasia typically is associated with comparable difficulties in written and spoken modalities of language expression and comprehension. In contrast, auditory verbal agnosia is the disproportionate difficulty comprehending spoken compared to written language, also typically greater than difficulties with spoken and written language expression, in the absence of a primary sensory deficit. The terms pure word deafness and auditory verbal agnosia are often used synonymously. However, the broader term of auditory agnosia more accurately reflects difficulty processing both speech and non-speech sounds whereas individuals with auditory verbal agnosia (pure word deafness) have preserved processing of environmental sounds. Auditory agnosia is reported in the stroke literature, but rarely reported in progressive neurologic disorders. Here, we report a case of a woman who presented with what is best described as a prominent auditory deficit in the context of an initially unclassifiable, or mixed, primary progressive aphasia (PPA) with accompanying apraxia of speech. Her clinical presentation shared features with auditory agnosia, although sensory functioning was not formally assessed. We report clinical and neuroimaging data spanning 6 years and subsequent autopsy results. She presented at 65 years of age, 5 years post onset of symptoms that included insidious and progressive difficulties thinking of words, constructing sentences, pronouncing words, and understanding instructions. She had disproportionate difficulty with comprehension of spoken compared to written language. She eventually developed features of the nonfluent/agrammatic variant of PPA, as well as an apraxia of speech. Imaging with [18F]-fluorodeoxyglucose (FDG)-PET revealed progression of bilateral (left greater than right) hypometabolism involving the frontal, temporal (predominantly the lateral superior gyrus), and parietal lobes, that eventually included the supplementary motor area, anterior cingulate, and caudate. Autopsy revealed pathological lesions consistent with corticobasal degeneration.
| S-EPMC6650352 | biostudies-literature
Project description:ImportanceGrammatical comprehension difficulty is an essential supporting feature of the non-fluent/agrammatic variant of primary progressive aphasia (naPPA), but well-controlled clinical measures of grammatical comprehension are unavailable.ObjectiveTo develop a measure of grammatical comprehension and examine this comparatively in PPA variants and behavioural-variant frontotemporal degeneration (bvFTD) and to assess the neuroanatomic basis for these deficits with volumetric grey matter atrophy and whole-brain fractional anisotropy (FA) in white matter tracts.DesignCase-control study.SettingAcademic medical centre.Participants39 patients with variants of PPA (naPPA=12, lvPPA=15 and svPPA=12), 27 bvFTD patients without aphasia and 12 healthy controls.Main outcome measureGrammatical comprehension accuracy.ResultsPatients with naPPA had selective difficulty understanding cleft sentence structures, while all PPA variants and patients with bvFTD were impaired with sentences containing a centre-embedded subordinate clause. Patients with bvFTD were also impaired understanding sentences involving short-term memory. Linear regressions related grammatical comprehension difficulty in naPPA to left anterior-superior temporal atrophy and reduced FA in corpus callosum and inferior frontal-occipital fasciculus. Difficulty with centre-embedded sentences in other PPA variants was related to other brain regions.Conclusions and relevanceThese findings emphasise a distinct grammatical comprehension deficit in naPPA and associate this with interruption of a frontal-temporal neural network.
| S-EPMC3925677 | biostudies-literature
Project description:ObjectiveTo determine the contribution of white matter hyperintensities (WMH) to language deficits while accounting for cortical atrophy in individuals with primary progressive aphasia (PPA).MethodForty-three individuals with PPA completed neuropsychological assessments of nonverbal semantics, naming, and sentence repetition plus T2-weighted and fluid-attenuated inversion recovery scans. Using three visual scales, we rated WMH and cerebral ventricle size for both scan types. We used Spearman correlations to evaluate associations between the scales and scans. To test whether visual ratings-particularly of WMH-are associated with language, we compared a base model (including gray matter component scores obtained via principal component analysis, age, and days between assessment and MRI as independent variables) with full models (ie, the base model plus visual ratings) for each language variable.ResultsVisual ratings were significantly associated within and between scans and were significantly correlated with age but not with other vascular risk factors. Only the T2 scan ratings were associated with language abilities. Specifically, controlling for other variables, poorer naming was significantly related to larger ventricles (P = 0.033) and greater global (P = 0.033) and periventricular (P = 0.049) WMH. High global WMH (P = 0.034) were also correlated with worse sentence repetition skills.ConclusionVisual ratings of global brain health were associated with language deficits in PPA independent of cortical atrophy and age. While WMH are not unique to PPA, measuring WMH in conjunction with cortical atrophy may elucidate more accurate brain structure-behavior relationships in PPA than cortical atrophy measures alone.
| S-EPMC7479763 | biostudies-literature
Project description:Background and purposeDysphagia is an important feature of neurodegenerative diseases and potentially life-threatening in primary progressive aphasia (PPA) but remains poorly characterized in these syndromes. We hypothesized that dysphagia would be more prevalent in nonfluent/agrammatic variant (nfv)PPA than other PPA syndromes, predicted by accompanying motor features, and associated with atrophy affecting regions implicated in swallowing control.MethodsIn a retrospective case-control study at our tertiary referral centre, we recruited 56 patients with PPA (21 nfvPPA, 22 semantic variant [sv]PPA, 13 logopenic variant [lv]PPA). Using a pro forma based on caregiver surveys and clinical records, we documented dysphagia (present/absent) and associated, potentially predictive clinical, cognitive, and behavioural features. These were used to train a machine learning model. Patients' brain magnetic resonance imaging scans were assessed using voxel-based morphometry and region-of-interest analyses comparing differential atrophy profiles associated with dysphagia presence/absence.ResultsDysphagia was significantly more prevalent in nfvPPA (43% vs. 5% svPPA and no lvPPA). The machine learning model revealed a hierarchy of features predicting dysphagia in the nfvPPA group, with excellent classification accuracy (90.5%, 95% confidence interval = 77.9-100); the strongest predictor was orofacial apraxia, followed by older age, parkinsonism, more severe behavioural disturbance, and more severe cognitive impairment. Significant grey matter atrophy correlates of dysphagia in nfvPPA were identified in left middle frontal, right superior frontal, and right supramarginal gyri and right caudate.ConclusionsDysphagia is a common feature of nfvPPA, linked to underlying corticosubcortical network dysfunction. Clinicians should anticipate this symptom particularly in the context of other motor features and more severe disease.
| S-EPMC11295169 | biostudies-literature
Project description:Overlapping clinical presentations in primary progressive aphasia (PPA) variants present challenges for diagnosis and understanding pathophysiology, particularly in the early stages of the disease when behavioral (speech) symptoms are not clearly evident. Divergent atrophy patterns (temporoparietal degeneration in logopenic variant lvPPA, frontal degeneration in nonfluent variant nfvPPA) can partially account for differential speech production errors in the two groups in the later stages of the disease. While the existing dogma states that neurodegeneration is the root cause of compromised behavior and cortical activity in PPA, the extent to which neurophysiological signatures of speech dysfunction manifest independent of their divergent atrophy patterns remain unknown. We test the hypothesis that nonword deficits in lvPPA and nfvPPA arise from distinct patterns of neural oscillations that are unrelated to atrophy. We use a novel structure-function imaging approach integrating magnetoencephalographic imaging of neural oscillations during a non-word repetition task with voxel-based morphometry-derived measures of gray matter volume to isolate neural oscillation abnormalities independent of atrophy. We find reduced beta band neural activity in left temporal regions associated with the late stages of auditory encoding unique to patients with lvPPA and reduced high-gamma neural activity over left frontal regions associated with the early stages of motor preparation in patients with nfvPPA. Neither of these patterns of reduced cortical oscillations was explained by cortical atrophy in our statistical model. These findings highlight the importance of structure-function imaging in revealing neurophysiological sequelae in early stages of dementia when neither structural atrophy nor behavioral deficits are clinically distinct.
| S-EPMC10472914 | biostudies-literature
Project description:ObjectiveTo relate fractional anisotropy (FA) changes associated with the semantic and logopenic variants of primary progressive aphasia (PPA) to measures of lexical retrieval.MethodsWe collected neuropsychological testing, volumetric magnetic resonance imaging, and diffusion-weighted imaging on semantic variant PPA (svPPA) (n = 11) and logopenic variant PPA (lvPPA) (n = 13) patients diagnosed using published criteria. We also acquired neuroimaging data on a group of demographically comparable healthy seniors (n = 34). FA was calculated and analyzed using a white matter (WM) tract-specific analysis approach. This approach utilizes anatomically guided data reduction to increase sensitivity and localizes results within canonically defined tracts. We used non-parametric, cluster-based statistical analysis to relate language performance to FA and determine regions of reduced FA in patients.ResultsWe found widespread FA reductions in WM for both variants of PPA. FA was related to both confrontation naming and category naming fluency performance in left uncinate fasciculus and corpus callosum in svPPA and left superior and inferior longitudinal fasciculi in lvPPA.ConclusionSvPPA and lvPPA are associated with distinct disruptions of a large-scale network implicated in lexical retrieval, and the WM disease in each phenotype may contribute to language impairments including lexical retrieval.
| S-EPMC3873600 | biostudies-literature
Project description:BackgroundA subset of patients with the nonfluent variant of primary progressive aphasia (PPA) exhibit concomitant single-word comprehension problems, constituting a 'mixed variant' phenotype. This phenotype is rare and currently not fully characterized. The aim of this study was twofold: to assess the prevalence and nature of single-word comprehension problems in the nonfluent variant and to study multimodal imaging characteristics of atrophy, tau, and amyloid burden associated with this mixed phenotype.MethodsA consecutive memory-clinic recruited series of 20 PPA patients (12 nonfluent, five semantic, and three logopenic variants) were studied on neurolinguistic and neuropsychological domains relative to 64 cognitively intact healthy older control subjects. The neuroimaging battery included high-resolution volumetric magnetic resonance imaging processed with voxel-based morphometry, and positron emission tomography with the tau-tracer [18F]-THK5351 and amyloid-tracer [11C]-Pittsburgh Compound B.ResultsSeven out of 12 subjects who had been classified a priori with nonfluent variant PPA showed deficits on conventional single-word comprehension tasks along with speech apraxia and agrammatism, corresponding to a mixed variant phenotype. These mixed variant cases included three females and four males, with a mean age at onset of 65 years (range 44-77 years). Object knowledge and object recognition were additionally affected, although less severely compared with the semantic variant. The mixed variant was characterized by a distributed atrophy pattern in frontal and temporoparietal regions. A more focal pattern of elevated [18F]-THK5351 binding was present in the supplementary motor area, the left premotor cortex, midbrain, and basal ganglia. This pattern was closely similar to that seen in pure nonfluent variant PPA. At the individual patient level, elevated [18F]-THK5351 binding in the supplementary motor area and premotor cortex was present in six out of seven mixed variant cases and in five and four of these cases, respectively, in the thalamus and midbrain. Amyloid biomarker positivity was present in two out of seven mixed variant cases, compared with none of the five pure nonfluent cases.ConclusionsA substantial proportion of PPA patients with speech apraxia and agrammatism also have single-word comprehension deficits. At the neurobiological level, the mixed variant shows a high degree of similarity with the pure nonfluent variant of PPA.Trial registrationEudraCT, 2014-002976-10 . Registered on 13-01-2015.
| S-EPMC6052568 | biostudies-literature
Project description:IntroductionIn primary progressive aphasia (PPA) patients with autopsy-confirmed Alzheimer's disease (AD) or frontotemporal lobar degeneration (FLTD), we tested how the core clinical features of logopenic PPA-naming and repetition-change over time and relate to pathologic burden.MethodsIn PPA with AD (n = 13) or FTLD (n = 16) pathology, Boston Naming Test and Forward Digit Span measured longitudinal naming and repetition; as reference, Mini-Mental State Examination (MMSE) measured global cognition. Pathologic burden in left peri-Sylvian regions was related to longitudinal cognitive decline.ResultsPPA with AD showed greater decline in naming (P = 0.021) and repetition (P = 0.020), compared to FTLD; there was no difference in MMSE decline (P = 0.99). Across all PPA, declining naming (P = 0.0084) and repetition (P = 0.011) were associated with angular, superior-middle temporal (naming P = 0.014; repetition P = 0.011) and middle frontal (naming P = 0.041; repetition P = 0.030) pathologic burden.DiscussionUnique longitudinal profiles of naming and repetition performance in PPA with AD are related to left peri-Sylvian pathology.
| S-EPMC8327471 | biostudies-literature
Project description:ObjectiveTo evaluate whether a quantitative speech measure is effective in identifying and monitoring motor speech impairment (MSI) in patients with primary progressive aphasia (PPA) and to investigate the neuroanatomical basis of MSI in PPA.MethodsSixty-four patients with PPA were evaluated at baseline, with a subset (n = 39) evaluated longitudinally. Articulation rate (AR), a quantitative measure derived from spontaneous speech, was measured at each time point. MRI was collected at baseline. Differences in baseline AR were assessed across PPA subtypes, separated by severity level. Linear mixed-effects models were conducted to assess groups differences across PPA subtypes in rate of decline in AR over a 1-year period. Cortical thickness measured from baseline MRIs was used to test hypotheses about the relationship between cortical atrophy and MSI.ResultsBaseline AR was reduced for patients with nonfluent variant PPA (nfvPPA) compared to other PPA subtypes and controls, even in mild stages of disease. Longitudinal results showed a greater rate of decline in AR for the nfvPPA group over 1 year compared to the logopenic and semantic variant subgroups. Reduced baseline AR was associated with cortical atrophy in left-hemisphere premotor and supplementary motor cortices.ConclusionsThe AR measure is an effective quantitative index of MSI that detects MSI in mild disease stages and tracks decline in MSI longitudinally. The AR measure also demonstrates anatomic localization to motor speech-specific cortical regions. Our findings suggest that this quantitative measure of MSI might have utility in diagnostic evaluation and monitoring of MSI in PPA.
| S-EPMC6511075 | biostudies-literature