Primary Progressive Aphasia Group Research Articles

Montreal Cognitive Assessment (MoCA) Performance and Domain-Specific Index Scores in Amnestic Versus Aphasic Dementia.

The Montreal Cognitive Assessment (MoCA) is a popular and simple-to-administer screening instrument to detect cognitive impairment. The MoCA generates a total score and six domain-specific index scores: (1) Memory, (2) Executive Functioning, (3) Attention, (4) Language, (5) Visuospatial, and (6) Orientation. It is unclear whether these MoCA scores can differentiate between distinct clinical dementia syndromes. This study compared MoCA Index scores between amnestic dementia of the Alzheimer's type (DAT) and primary progressive aphasia (PPA), a language-based dementia. Baseline MoCA data were analyzed from 33 DAT, 37 PPA, and 83 cognitively normal individuals enrolled in the Clinical Core of the Northwestern Alzheimer's Disease Center. A one-way analysis of covariance adjusted for age was used to compare MoCA scores among groups. A logistic regression model was implemented to observe individual likelihood of group affiliation based on MoCA Index scores. The mean MoCA total score was significantly higher in controls compared to both patient groups (p < .001) but did not differ between DAT and PPA groups. However, in accordance with salient clinical features commonly observed in DAT versus PPA, Memory and Orientation Index scores were lowest in the DAT group (p < .001), whereas Language and Attention Index scores were lowest in the PPA group (p < .001). Multivariate logistic regression analysis showed that the individual effects of Memory (p = .001), Language (p = .002), and Orientation (p = .025) Indices were significant. MoCA Index scores can help differentiate among distinct cognitive syndromes, suggesting it may be a useful brief screening tool to detect domain-specific cognitive impairment.

Using narratives in differential diagnosis of neurodegenerative syndromes

PurposeLanguage decline has been associated with healthy aging and with various neurodegenerative conditions, making it challenging to differentiate among these conditions. This study examined the utility of linguistic measures derived from a short narrative language sample for 1) identifying language characteristics and cut-off scores to differentiate between healthy aging, Primary Progressive Aphasia (PPA), Mild Cognitive Impairment (MCI), and Alzheimer’s dementia (AD); and 2) differentiating among PPA variants in which language is the primary impairment. MethodParticipants were 25 neurologically healthy English speakers, 20 individuals with MCI, 20 with AD, and 26 with PPA (non-fluent/agrammatic N = 10, logopenic N = 9, semantic N = 7). Narrative language samples of the Cookie Theft Picture of persons with healthy aging, MCI and AD were retrospectively obtained from the DementiaBank database (https://talkbank.org/DementiaBank/) and PPA samples were obtained from an ongoing research study. The language samples were analyzed for fluency, word retrieval success, grammatical accuracy, and errors using automated and manual analysis methods. The sensitivity and specificity of various language measures was computed. ResultsParticipants with PPA scored lower than neurologically healthy and MCI groups on fluency (words per minute and disfluencies), word retrieval (Correct Information Units and number of errors), and sentence grammaticality. PPA and AD groups did not differ on language measures. Agrammatic PPA participants scored lower than logopenic and semantic PPA groups on several measures, while logopenic and semantic PPA did not differ on any measures. ConclusionMeasures derived from brief language samples and analyzed using mostly automated methods are clinically useful in differentiating PPA from healthy aging and MCI, and agrammatic PPA from other variants. The sensitivity and specificity of these measures is modest and can be improved when coupled with clinical presentation.

Differential neurocognitive network perturbation in amnestic and aphasic Alzheimer disease.

To determine if Alzheimer disease (AD) is associated with aphasic rather than amnestic dementias in certain circumstances related in part to perturbations in different networks. Three groups were investigated: 14 participants suspected of having the neuropathology of AD based on clinically diagnosed amnestic dementia of the Alzheimer type (DAT), 26 individuals with primary progressive aphasia (PPA) with either a positive 18F-florbetapir amyloid PET scan or confirmed AD at autopsy, and 26 neurologically intact controls. The groups were compared using rs-fMRI. Seeds included the left hemisphere inferior frontal gyrus (IFG) for the language network, the left hippocampus for the episodic memory network, and the left posterior cingulate for the default mode network (DMN). Greater connectivity perturbations were found from the hippocampus for the DAT group and from the IFG for the PPA group. Furthermore, connectivity alterations in the PPA group were more asymmetric and favored the language-dominant left hemisphere. Loss of connectivity from the DMN seed was of a similar magnitude in the PPA and DAT groups. Despite the presumptive common underlying neuropathology of amyloid plaques and neurofibrillary tangles, the 2 groups displayed 2 different patterns of network perturbation, each concordant with the clinical presentation and the anatomy of neurodegeneration.

Perturbations of language network connectivity in primary progressive aphasia

Aphasias are caused by disruption in structural integrity and interconnectivity within a large-scale distributed language network. We investigated the distribution and behavioral consequences of altered functional connectivity in three variants of primary progressive aphasia (PPA). The goal was to clarify relationships among atrophy, resting connectivity, and the resulting behavioral changes in 73 PPA and 33 control participants. Three core regions of the left perisylvian language network: the inferior frontal gyrus (IFG), middle temporal gyrus (MTG), and anterior temporal lobe (ATL) were evaluated in agrammatic (PPA-G), logopenic (PPA-L), and semantic (PPA-S) PPA variants. All PPA groups showed decreased connectivity between IFG and MTG. The PPA-S group also showed additional loss of connectivity strength between ATL and the other language regions. Decreased connectivity between the IFG and MTG nodes in PPA-G remained significant even when controlled for the effect of atrophy. In the PPA group as a whole, IFG-MTG connectivity strength correlated with repetition and grammar scores, whereas MTG-ATL connectivity correlated with picture naming and single-word comprehension. There was no significant change in the connectivity of homologous regions in the right hemisphere. These results show that language impairments in PPA are associated with perturbations of functional connectivity within behaviorally concordant components of the language network. Altered connectivity in PPA may reflect not only the irreversible loss of cortical components indexed by atrophy, but also the dysfunction of remaining neurons.

Clustering Analysis of FDG-PET Imaging in Primary Progressive Aphasia.

Background: Primary progressive aphasia (PPA) is a clinical syndrome characterized by the neurodegeneration of language brain systems. Three main clinical forms (non-fluent, semantic, and logopenic PPA) have been recognized, but applicability of the classification and the capacity to predict the underlying pathology is controversial. We aimed to study FDG-PET imaging data in a large consecutive case series of patients with PPA to cluster them into different subtypes according to regional brain metabolism.Methods: 122 FDG-PET imaging studies belonging to 91 PPA patients and 28 healthy controls were included. We developed a hierarchical agglomerative cluster analysis with Ward's linkage method, an unsupervised clustering algorithm. We conducted voxel-based brain mapping analysis to evaluate the patterns of hypometabolism of each identified cluster.Results: Cluster analysis confirmed the three current PPA variants, but the optimal number of clusters according to Davies-Bouldin index was 6 subtypes of PPA. This classification resulted from splitting non-fluent variant into three subtypes, while logopenic PPA was split into two subtypes. Voxel-brain mapping analysis displayed different patterns of hypometabolism for each PPA group. New subtypes also showed a different clinical course and were predictive of amyloid imaging results.Conclusion: Our study found that there are more than the three already recognized subtypes of PPA. These new subtypes were more predictive of clinical course and showed different neuroimaging patterns. Our results support the usefulness of FDG-PET in evaluating PPA, and the applicability of computational methods in the analysis of brain metabolism for improving the classification of neurodegenerative disorders.

Cognitive Reserve Hypothesis in Frontotemporal Dementia: Evidence from a Brain SPECT Study in a Series of Greek Frontotemporal Dementia Patients

Background and Objective: Cognitive reserve (CR) mediates the clinical expression of brain pathology in Alzheimer’s disease, while there are much less relevant data in frontotemporal dementia (FTD). In the present study we examined whether CR, measured using the Cognitive Reserve Index (CRI), correlated with regional cerebral blood flow (rCBF) in Greek FTD patients. Methods: Eighty FTD patients, i.e., 47 with behavioral variant FTD (bvFTD) and 33 with primary progressive aphasia (PPA), were enrolled into this study. CR was assessed using the CRI questionnaire, which provides a total score (CRI) and 3 subscores, i.e., CRI-education, CRI-working activity, and CRI-leisure time. The FTD-Clinical Dementia Rating Scale was used to assess the severity of dementia and a brain SPECT study was performed to measure rCBF. Finally, multiple regression analyses were conducted to explore correlations between CR indices and frontotemporal rCBF. Results: In both the bvFTD and the PPA groups, higher scores in the CRI, CRI-education, and CRI-leisure time correlated with lower rCBF in the bilateral frontal and left temporal cortex, respectively, controlling for age, sex, time since symptom onset, and disease severity. Conclusion: In the present study, lifetime participation in leisure time activities was found to mitigate the burden of disease in bvFTD and PPA patients. Moreover, FTD patients with a higher educational attainment were able to cope better with greater brain damage. Determination of the most suitable activities to build an adequate level of CR is crucial for dementia prevention.

Plasma tau is increased in frontotemporal dementia

BackgroundFrontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder presenting clinically with personality change (behavioural variant FTD (bvFTD)) or language deficits (primary progressive aphasia (PPA)). About a third of FTD is...

Differentiating between subtypes of primary progressive aphasia and mild cognitive impairment on a modified version of the Frontal Behavioral Inventory.

Behavioral assessment has been investigated in frontotemporal lobar degeneration and Alzheimer’s disease, but has not been explored extensively in subtypes of primary progressive aphasia (PPA). We explored the ability of a modified version of the Frontal Behavioral Inventory (FBI-mod) to discriminate between patients with distinct subtypes of PPA and patients with mild cognitive impairment (MCI). We hypothesized that individuals with nonfluent agrammatic PPA (nfaPPA) would have higher negative behavior scores than other groups and that individuals with semantic variant PPA (svPPA) would have higher disinhibition scores than other groups. Family members and/or caregivers of 120 individuals with PPA and MCI (mean age 69.54+8.75 years; 65 (54%) female; education 16.06±2.68 years; disease duration 46.47±34.26 months) completed the FBI-mod [logopenic PPA (lvPPA) n = 40. nfaPPA n = 29, svPPA n = 27, MCI n = 24]. The groups were not significantly different in age, gender, education, or disease duration. There were no significant differences between the groups for negative behaviors (p = 0.72) and disinhibition scores (p = 0.14). When comparing negative and disinhibition scores (in percent), negative scores were significantly higher in all groups (p < 0.001). When comparing subtest items, there was a pairwise difference between lvPPA and svPPA for restlessness (lvPPA < svPPA, p = 0.02, after adjusting for multiple between-group comparisons). There was a significant difference in the proportion of severe neglect between the groups with lvPPA having a lower proportion than the other two variants (p = 0.05), and there was a significant difference in the proportion of severe poor judgment between the groups with lvPPA also having a lower proportion than nfaPPA (p = 0.04). This study reveals the greater negative behavioral disturbance than disinhibition in the PPA and MCI groups of similar age and duration since onset and identifies different profiles for some specific behaviors for the PPA groups. These findings may have clinical and practical implications.

COMPARISON OF HYPOMETABOLISM AND CORTICAL ATROPHY IN PRIMARY PROGRESSIVE APHASIA

Recent diagnostic criteria for Primary Progressive Aphasia (PPA) include neuroimaging as a supportive feature [Gorno-Tempini et al., 2011]. The regional overlap between atrophy (measured by structural MRI) and hypometabolism (measured by FDG-PET) may vary throughout the PPA spectrum. Comparison of territories affected by atrophy and hypometabolism will shed light on the sequence of pathophysiological changes in the disease. We hypothesized that subtle hypometabolism is detectable in the PPA affected language regions which do not yet show cortical atrophy. 30 right-handed PPA patients (10 logopenic, 11 non-fluent agrammatic, 9 semantic) underwent FDG-PET scan within 12 months from structural MRI scan. PET was co-registered to MRI and glucose uptake was quantified by standardized uptake value ratios (SUVR) with pons as reference region. MRI scans were analyzed according to FreeSurfer pipeline. SUVR and cortical thickness values were projected to surfaces in fsaverage space. Hypometabolism and atrophy Z-maps were calculated based on a set of 30 age and sex matched controls from Harvard Aging Brain Study [Dagley et al., 2015]. Hypometabolism and cortical atrophy were localized to mainly left hemispheric regions involved in language dysfunction in PPA. In frontal and parietal language areas, regions with cortical atrophy were smaller and contained within regions displaying hypometabolism. Temporal areas were affected by hypometabolism and atrophy to comparable extent. Quantitatively, FDG Z-scores were lower than cortical thickness Z-scores in frontal and parietal language areas on the left and right. In temporal areas cortical thickness Z-scores were lower than FDG Z-scores, only on the left. Control region and other regions did not show significant differences. The pattern of regional differences between FDG and cortical thickness Z-scores in logopenic and non-fluent agrammatic subtypes resembled the pattern of differences in the whole PPA group. Semantic PPA patients had lower cortical thickness Z-scores than FDG Z-scores in temporal areas in both hemispheres. Our data suggest that hypometabolism is present without co-occurring atrophy in parts of the PPA affected language regions, which likely indicate future disease spread. Hypometabolism reflects synaptic and neuronal dysfunction, therefore, may occur earlier than cortical atrophy which represents neuronal death.

SERUM FERRITIN IS INCREASED IN A SUBSET OF PATIENTS WITH FRONTOTEMPORAL DEMENTIA

Frontotemporal dementia (FTD) is a common cause of early-onset dementia. Recent studies have shown a role for inflammation and an altered immune response in FTD. Serum levels of ferritin, an iron carrier and storage protein, are increased in inflammatory disorders and can therefore be a surrogate marker of inflammation. In this study we aimed to evaluate whether serum ferritin levels are increased in patients with FTD. Using a latex fixation test we measured ferritin levels in serum samples of 133 patients meeting diagnostic criteria for an FTD spectrum disorder (60 behavioural variant FTD, 6 FTD with motor neurone disease (MND), 23 semantic variant primary progressive aphasia (PPA), 31 nonfluent variant PPA, 8 PPA-not otherwise specified, 4 with corticobasal syndrome/progressive supranuclear palsy, 1 with inclusion body myositis with Paget's disease and FTD) as well as 16 patients with logopenic variant PPA and 26 healthy controls. Pathological and genetic status (presence of GRN, C9orf72, MAPT, TBK1, VCP, SQSTM1mutations) was noted when available. No significant difference in age or gender was seen between the groups. Mean (standard deviation) ferritin levels (ng/ml) in the FTD group were 115.4 (111.0), 113.0 (85.5) in the logopenic variant PPA group and 80.7 (55.2) in the controls. Although there was no significant difference between the disease groups there was a subset of patients with FTD with very high ferritin levels. Stratifying the FTD cohort according to clinical diagnosis, patients with FTD-MND (134.9 (136.5)) had the highest levels. 40 patients had tested positive for genetic mutations: the GRN mutation group (n=9) had the highest ferritin levels (164.5 (186.3), followed by individuals with C9orf72(n=16) mutations (115.9 (129.8)). Combining genetic and pathological cases, levels were higher in those with definite or likely TDP-43 pathology (n=29: 142.0 (149.1)) compared to individuals with tau pathology (n=13: 96.3 (79.0)). Ferritin concentration did not correlate with disease duration in any of the groups. This study shows a trend for increased serum ferritin levels in FTD, particularly in those with TDP-43opathies, including those clinically with FTD-MND and genetically with GRN and C9orf72 mutations. This study adds further evidence for the role of inflammation in FTD.

Group intervention for individuals with primary progressive aphasia and their spouses: Who comes first?

Primary progressive aphasia (PPA) is a neurodegenerative dementia in which language impairment is the first and most dominant symptom. There is a considerable dearth of interventions for PPA although language rehabilitation has made headway in managing the disorder. Thus far, no comprehensive services have been proposed for PPA clients and/or their spouses. This paper describes the first structured group intervention program designated exclusively for people with PPA and their caregivers. This pilot project originates from a clinical service and presents supporting evidence for initiation of a larger study to establish an evidence-based intervention for PPA. A 10-week intervention program comprised working on language activities, learning communication strategies, counselling and education. Outcome measures administered to participants and their spouses before and after the intervention were compared showed improvements in quality of communication and coping skills in the PPA group compared to controls. Qualitative comments from all 10 participants in the active treatment group highlighted the necessity of intervention that is tailored specifically to the PPA population and addresses the needs of both individuals with PPA and their caregivers. All participants in the intervention group contributed to the study and are also co-authors of this paper.

Cholinergic depletion and basal forebrain volume in primary progressive aphasia.

Primary progressive aphasia (PPA) is a heterogeneous syndrome with various neuropathological causes for which no medical treatment with proven efficacy exists. Basal forebrain (BF) volume loss has been reported in PPA but its relation to cholinergic depletion is still unclear. The primary objective of this study was to investigate whether cholinergic alterations occur in PPA variants and how this relates to BF volume loss. An academic memory clinic based consecutive series of 11 PPA patients (five with the semantic variant (SV), four with the logopenic variant (LV) and two with the nonfluent variant (NFV)) participated in this cross-sectional in vivo PET imaging study together with 10 healthy control subjects. Acetylcholinesterase (AChE) activity was quantitatively measured in the neo- and allocortex using N-[11C]-Methylpiperidin-4-yl propionate (PMP)-PET with arterial sampling and metabolite correction. Whole brain and BF volumes were quantified using voxel-based morphometry on high-resolution magnetic resonance imaging (MRI) scans.In the PPA group, only LV cases showed decreases in AChE activity levels compared to controls. Surprisingly, a substantial number of SV cases showed significant AChE activity increases compared to controls. BF volume did not correlate with AChE activity levels in PPA. To conclude, in our sample of PPA patients, LV but not SV was associated with cholinergic depletion. BF atrophy in PPA does not imply cholinergic depletion.

Frontotemporal Lobar Degeneration-Modified Clinical Dementia Rating (FTLD-CDR) Scale and Frontotemporal Dementia Rating Scale (FRS) Correlation With Regional Brain Perfusion in a Series of FTLD Patients.

Severity assessment scales for frontotemporal lobar degeneration (FTLD) have been recently introduced. In the present study, the authors examined whether the FTLD-modified Clinical Dementia Rating (FTLD-CDR) scale and the Frontotemporal Dementia Rating Scale (FRS) correlated with regional brain perfusion in Greek FTLD patients. A total of 47 behavioral variant frontotemporal dementia (bvFTD) patients and 33 primary progressive aphasia (PPA) patients were assessed for demographic data, cognitive reserve (CR), and severity of dementia and underwent brain single-photon emission computed tomography. Both scales were valid in the bvFTD group, predicting frontal lobe perfusion. In the PPA group, both scales were found to predict temporal hypoperfusion only after accounting for CR, which could imply a potential role for reserve in PPA patients.

Is in vivo amyloid distribution asymmetric in primary progressive aphasia?

We aimed to determine whether (18) F-florbetapir amyloid positron emission tomography imaging shows a clinically concordant, left-hemisphere-dominant pattern of deposition in primary progressive aphasia (PPA). Elevated cortical amyloid (Aβ(+) ) was found in 19 of 32 PPA patients. Hemispheric laterality of amyloid burden was compared between Aβ(+) PPA and an Aβ(+) amnestic dementia groups (n = 22). The parietal region showed significantly greater left lateralized amyloid uptake in the PPA group than the amnestic group (p < 0.007), consistent with the left lateralized pattern of neurodegeneration in PPA. These results suggest that the cortical distribution of amyloid may have a greater clinical concordance than previously reported.

Behavioral Evolution of Progressive Semantic Aphasia in Comparison with Nonfluent Aphasia

Background: Patients with primary progressive aphasia (PPA) usually develop significant behavioral disturbances with progression of the disease. We tested our clinical observation that development of disruptive agitation is more likely in semantic than in nonfluent PPA and examined which clinical variables could be associated with this behavior. Methods: We retrospectively analyzed neuropsychiatric scores and the need for behavioral treatments in semantic PPA (n = 41) and nonfluent PPA (n = 39) cases and compared first (1-3 years since the onset of symptoms) and last (5-13 years since the onset) evaluations. Clinical variables and laterality of temporal atrophy were associated with symptoms in semantic PPA cases. Results: The semantic PPA group developed more frequent (p = 0.03) and intense agitation (p = 0.0008) and had a greater need for antipsychotic drugs (p = 0.001) than the nonfluent PPA group. Presence of agitation was clearly associated with psychotic symptoms (delusions/hallucinations) but was not associated with gender, age at onset, duration of the disease, or laterality of temporal atrophy. In contrast, nonfluent PPA cases were more frequently depressed and treated with antidepressants (p = 0.0007). There were no differences in anxiety, irritability, apathy, perseverations, hyperorality, or abnormal motor behavior. Conclusions: Semantic PPA in advanced disease is frequently associated with agitation and psychotic symptoms with fewer mood symptoms, while nonfluent PPA maintains a high prevalence of depression. This implies different treatment and care and support needs for each group.

Naming vs knowing faces in primary progressive aphasia

This study examines the anatomical correlates of naming vs recognizing faces using a novel measure that utilizes culturally relevant and age-appropriate items, the Northwestern University Famous Faces (NUFFACE) Test, in primary progressive aphasia (PPA), a syndrome characterized by progressive language deficits and associated with cortical atrophy in areas important for word and object representations. NUFFACE Test performance of 27 controls (mean age 62.3 years) was compared with that of 30 patients with PPA (mean age 62 years). Associations between NUFFACE Test performance and cortical thickness measures were quantified within the PPA group. Patients with PPA displayed significant impairment on the NUFFACE Test, demonstrating that it is a useful measure of famous-face identification for individuals with relatively young-onset dementias. Despite widespread distribution of atrophy in the PPA group, face naming impairments were correlated with atrophy of the left anterior temporal lobe while face recognition impairments were correlated with bitemporal atrophy. In addition to their clinical relevance for highlighting the distinction between face naming and recognition impairments in individuals with young-onset dementia, these findings add new insights into the dissociable clinico-anatomical substrates of lexical retrieval and object knowledge.

Behavioral disturbances differentiate frontotemporal lobar degeneration subtypes and Alzheimer's disease: evidence from the Frontal Behavioral Inventory

Behavioral assessment is useful for the diagnosis of frontotemporal lobar degeneration (FTLD). We explored the ability of the Frontal Behavioral Inventory (FBI) to discriminate between patients with distinct subtypes of FTLD and patients with Alzheimer's disease (AD), as well as the influence of demographic variables on FBI scores. The FBI was administered to the caregivers of 87 patients diagnosed with FTLD [64 behavioral variant FTLD, 19 aphasic variant FTLD (primary progressive aphasia), and 4 motor/extrapyramidal variant (corticobasal syndrome)] and 30 patients with AD. Patients with AD were older than patients with FTLD. The two groups did not differ with respect to duration of illness, level of education, or sex ratio. Age significantly predicted disinhibited positive behaviors, such as perseverations and irritability, whereas education did not contribute to FBI ratings. Classification accuracy for the discrimination of AD and mixed FTLD groups was 81%. Moreover, 88.3% and 83.7% accuracy was achieved for the discrimination of AD and behavioral variant FTLD, and AD and primary progressive aphasia groups, respectively. The Total Negative subscale of the FBI, which summarizes the presence of deficit (negative) behaviors, was the best discriminator. A cut-off score of 17 provided 83% sensitivity and 98% specificity in distinguishing between FTLD and AD patients. The FBI is a sensitive and specific tool for the differential diagnosis of FTLD from AD. The optimal cut-off point for the detection of FTLD patients was lower than that initially proposed.

Abnormalities of connected speech in the non-semantic variants of primary progressive aphasia

Background: The importance of connected speech analysis in the diagnosis and further classification of primary progressive aphasia (PPA) is becoming apparent. However, methodological inconsistencies in elicitation and analysis of speech samples hinder comparison of different laboratories' results. The recent recommendations for further classification of PPA have characterised three main variants, but we have demonstrated that a considerable proportion of patients do not conform to any of these, as their language deficits extend beyond those of a single syndromic variant (mixed PPA). This report is an attempt to characterise the language profiles of different non-semantic variants of PPA using a combination of connected speech analysis and standard neuropsychological tests. Aims: Our aims were (a) to assess the relative efficacy of semi-structured interviews and picture description tasks in revealing the important aspects of language deficit in our patient groups, (b) to document the language profile of a mixed PPA group for the first time, (c) to compare the patterns of speech abnormality in non-fluent variant and mixed PPA, relative to each other and to normal control participants, and (d) to identify those features of spontaneous speech decline that are frequent and tangible enough to be detected during clinical consultations. Methods & Procedures: Connected speech samples obtained from picture description and semi-structured interviews were analysed quantitatively and the outcomes were contrasted between the elicitation methods and among the participant groups. Due to a very small number of cases fulfilling criteria for logopaenic PPA, the speech of these patients was scrutinised individually. Outcomes & Results: Pair-wise comparisons of the two speech elicitation methods at a group level revealed only a partial concordance and greater sensitivity of semi-structured interviews in detecting different aspects of speech abnormality. At a group level there was a significant impairment in the morpho-syntactic aspects of connected speech in both non-fluent and mixed PPA. A statistically significant difference from controls was observed in the semantic measures of discourse only in the mixed PPA group. Clinically useful features that differentiate both non-fluent and mixed PPA groups from healthy volunteers were decreased speech rate, shorter utterances, fewer complex grammatical structures, lack of spontaneity, more non-sentential speech units (elliptical and abandoned units), more hesitation markers, and, to a lesser extent, more phonological errors and editing breaks. Conclusions: The combination of the present results with those from our previous report on semantic dementia that used the same methodology offers a quantitative detailed assessment of connected speech across the spectrum of PPA.

The atrophy pattern in the subtypes of frontotemporal lobar degeneration and Alzheimer disease by structural MRI

Objective To analyze the patterns of cortical atrophy of the two subtypes of frontotemporal lobar degeneration (FTLD ),behavioural-vsriant frontotemporal dementia (bvFTD ) and primary progressive aphasia (PPA).And to compare them with that of Alzheimer disease (AD) to provide an objective basis for early diagnosis and differential diagnosis.Methods A total of 83 patients were enrolled in this study and there were 30 patients with cognitively normal controls (CN),30 with AD and 23 with FTLD (10 with bvFTD,13 with PPA).Philips 3.0 T TX scanner and 8 channel head coil was employed.Three dimensional turbo fast echo(3D-TFE)T1WI sequence with high resolution was used to collect the volume data of gray matter.3D-TFE T1 WI images were normalized and segmented into gray matter map for statistical analysis by SPM 8 and VBM 8.The false discovery rate (FDR) was adopted in P value adjustment,P ＜ 0.001,and the cluster size was set at 5.The full width at half maximum (FWHM ) was set at 4 mm for the smoothing.Paired t test was used for statistics.Results In bvFTD,PPA and AD groups,there were diffuse regions with reduced volume in cerebral cortex and subcortical structures (such as the hippocampus,the amygdala,the caudate nuclei,et al).The most obvious atrophic region in bvFTD and PPA group was found in the frontotemporal.Compared with AD,gray matter atrophy in bvFTD was found in brain regions including bilateral temporal lobes,bilateral superior temporal pole gyri,bilateral middle temporal pole gyri,right fusiform gyrus and bilateral frontal lobes.Among them,temporal and frontal lobes atrophy had obvious right partial lateralizing,with 14 301 voxels in right temporal lobe and 5105 in left (t =-5.03,P＜0.05).The number of atrophy voxels in right and left frontal lobe were 1344 and 125 (t =3.45,P ＜0.05).The left temporooccipital lobe atrophy was more obvious than the right in PPA,with 15 637 voxels in left and 10 723 in right ( t =- 2.65,P ＜ 0.05 ).Conclusions There are different brain gray matter atrophy patterns in bvFD,PPA and AD.Among them,bvFTD has asymmetric right frontal and temporal lobe atrophy,which may be related to characteristic personality changes.On the other hand,the asymmetric atrophy in left temporooccipital lobe may be responsible for the aphasis of patients with PPA. Key words: Dementia; Aphasia,primary progressive; Alzheimer disease; Magnetic resonance imaging; Comparative study

Verb and noun deficits in stroke-induced and primary progressive aphasia: The Northwestern Naming Battery

Background: Word class naming deficits are commonly seen in aphasia resulting from stroke (StrAph) and primary progressive aphasia (PPA), with differential production of nouns (objects) and verbs (actions) found based on StrAph type or PPA variant for some individuals. However, studies to date have not compared word class naming (or comprehension) ability in the two aphasic disorders. In addition there are no available measures for testing word class deficits, which control for important psycholinguistic variables across language domains. This study examined noun and verb production and comprehension in individuals with StrAph and PPA using a new test, the Northwestern Naming Battery (NNB; Thompson & Weintraub, experimental version), developed explicitly for this purpose. In addition we tested verb type effects, based on verb argument structure characteristics, which also is addressed by the NNB. Method: A total of 52 participants with StrAph (33 agrammatic, Broca's (StrAg); 19 anomic (StrAn)) and 28 PPA(10 agrammatic (PPA-G); 14 logopenic (PPA-L); 4 semantic (PPA-S)) were included in the study. Nouns and verbs were tested in the Confrontation Naming and Auditory Comprehension subtests of the NNB, with scores used to compute noun to verb ratios as well as performance by verb type. Performance patterns within and across StrAph and PPA groups were then examined. The external validity of the NNB was also tested by comparing (a) NNB Noun Naming scores to the Boston Naming Test (BNT; Kaplan, Goodglass, & Weintraub, 2001) and Western Aphasia Battery (WAB-R; Kertesz, 2007) Noun Naming subtest scores, (b) NNB Verb Naming scores to the Boston Diagnostic Aphasia Examination (BDAE; Goodglass, Kaplan, & Barresi, 2001) Action Naming score (for StrAph participants only), and (c) NNB Comprehension subtest scores to WAB-R Auditory Comprehension subtest scores. Outcomes & Results: Both agrammatic (StrAg and PPA-G) groups showed significantly greater difficulty producing verbs compared to nouns, but no comprehension impairment for either word class, whereas three of the four PPA-S participants showed poorer noun compared to verb production, as well as comprehension. However, neither the StrAn nor the PPA-L participants showed significant differences between the two word classes in production or comprehension. In addition, similar to the agrammatic participants, the StrAn participants showed a significant transitivity effect, producing intransitive (one-argument) verbs with greater accuracy than transitive (two- and three-argument) verbs. However, no transitivity effects were found for the PPA-L or PPA-S participants. There were significant correlations between NNB scores and all external validation measures. Conclusions: These data indicate that the NNB is sensitive to word class deficits in stroke and neurodegenerative aphasia. This is important both clinically for treatment planning and theoretically to inform both psycholinguistic and neural models of language processing.