Primary Progressive Aphasia Subtypes Research Articles

Beyond language impairment: Profiles of apathy in primary progressive aphasia

Primary progressive aphasia (PPA) is characterised by predominant language and communication impairment. However, behavioural changes, such as apathy, are increasingly recognised. Apathy is defined as a reduction in motivation and goal-directed behaviour. Recent theoretical models have suggested that apathy can be delineated into multiple dimensions: executive apathy (i.e., deficits in maintaining goals and organisation), emotional apathy (i.e., emotional blunting and indifference) and initiation apathy (i.e., reduced self-initiation). Whether the nature of apathy differs between clinical variants of PPA, and across early and late disease stages, remains to be established. Here, carers/informants of 20 semantic variant PPA (svPPA), 15 non-fluent variant PPA (nfvPPA), 16 logopenic variant PPA (lvPPA) and 25 healthy older controls completed the Dimensional Apathy Scale to quantify executive, emotional and initiation apathy. Voxel-based morphometry was used to identify associations between dimensions of apathy and regions of grey matter intensity decrease. Our behavioural results showed greater executive and initiation apathy in late svPPA than in late nfvPPA patients, while late svPPA had greater emotional apathy than both late nfvPPA and late lvPPA groups. Executive and initiation apathy were significantly higher than premorbid levels in all PPA subtypes, while elevated emotional apathy was only seen in early and late svPPA. Distinct neural correlates were identified across apathy dimensions. Executive apathy correlated with grey matter intensity of the left dorsolateral prefrontal and inferior parietal cortices; emotional apathy with the left medial prefrontal, insular and cerebellar regions; and initiation apathy with right parietal areas. Our findings are the first to reveal evidence of the dimensional nature of apathy in PPA, with different clinical signatures observed for each subtype. From a clinical standpoint, these results will inform the development of targeted interventions for specific aspects of apathy which emerge in PPA.

Thematic Integration Impairments in Primary Progressive Aphasia: Evidence From Eye-Tracking.

Primary progressive aphasia (PPA) is a degenerative disease affecting language while leaving other cognitive facilities relatively unscathed. The agrammatic subtype of PPA (PPA-G) is characterized by agrammatic language production with impaired comprehension of noncanonical filler-gap syntactic structures, such as object-relatives [e.g., The sandwich that the girl ate (gap) was tasty], in which the filler (the sandwich) is displaced from the object position within the relative clause to a position preceding both the verb and the agent (the girl) and is replaced by a gap linked with the filler. One hypothesis suggests that the observed deficits of these structures reflect impaired thematic integration, including impaired prediction of the thematic role of the filler and impaired thematic integration at the gap, but spared structure building (i.e., creation of the gap). In the current study, we examined the on-line comprehension of object-relative and subject-relative clauses in healthy controls and individuals with agrammatic and logopenic PPA using eye-tracking. Eye-movement patterns in canonical subject-relative clause structures were essentially spared in both PPA groups. In contrast, eye-movement patterns in noncanonical object-relative clauses revealed delayed thematic prediction in both agrammatic and logopenic PPA, on-time structure building (i.e., gap-filling) in both groups, and abnormal thematic integration in agrammatic, but not logopenic, PPA. We argue that these results are consistent with the hypothesis that agrammatic comprehension deficits reflect impaired thematic integration.

A ‘Mini Linguistic State Examination’ to Classify Primary Progressive Aphasia

Background: There are few available methods for qualitatively evaluating patients with primary progressive aphasia (PPA). Commonly adopted approaches are time-consuming, of limited accuracy, or designed to assess different patient populations. This paper introduces a new clinical test - the Mini Linguistic State Examination (MLSE) - which was designed uniquely to enable a clinician to assess and subclassify both classical and mixed presentations of PPA. The adoption of a novel assessment method (error classification) greatly amplifies the clinical information that can be derived from a set of standard linguistic tasks and allows a five-dimensional profile to be defined. Methods: Fifty-four patients and 30 matched controls were recruited. Five domains of language competence (motor speech, phonology, semantics, syntax, and working memory) were assessed using a sequence of 11 distinct linguistic assays. A random forest classification was used to assess the diagnostic accuracy for predicting PPA subtypes and create a decision tree as a guide to clinical classification. Findings: The random forest prediction model was 96% accurate overall (92% for logopenic variant, 93% for semantic variant, and 98% for non-fluent variant PPA). The derived decision tree produced a correct classification of 91% of participants whose data were not included in the training set. Interpretation: The MLSE is a new cognitive test incorporating a novel and powerful, yet straightforward, approach to scoring. Rigorous assessment of its diagnostic accuracy confirmed excellent matching of PPA syndromes to clinical gold standard diagnoses. Adoption of the MLSE by clinicians will have a decisive impact on the consistency and uniformity with which patients can be described clinically. It will also facilitate screening for cohort-based research, including future therapeutic trials, and is suitable for describing, quantifying and monitoring language deficits in other brain disorders. Funding Information: The research was funded by a Medical Research Council Research Grant award (Ref MR/N025881/1) to PG, MLR JR, KP and SC. Additional support was provided through grants from the MRC (UAG051 and G101400), Wellcome Trust (103838) and ERC (GAP: 670428), and through funding awarded to the National Institute for Health Research Cambridge Biomedical Research Centre and to the MRC CBU (MC_UU_00005/18). Declaration of Interests: JBR reports consultancy unrelated to the work with Biogen, UCB, Asceneuron and Althira; and receipt of research grants, unrelated to this work, from Janssen, AZ-Medimmune, and Lilly. The other authors declare no conflicts of interest. Ethics Approval Statement: Written informed consent was provided by all participants. The study protocol was reviewed and approved by the London (Chelsea) Research Ethics Committee [Ref. 16/LO/1735].

Automated profiling of spontaneous speech in primary progressive aphasia and behavioral-variant frontotemporal dementia: An approach based on usage-frequency

Language production provides important markers of neurological health. One feature of impairments of language and cognition, such as those that occur in stroke aphasia or Alzheimer's disease, is an overuse of high frequency, “familiar” expressions. We used computerized analysis to profile narrative speech samples from speakers with variants of frontotemporal dementia (FTD), including subtypes of primary progressive aphasia (PPA). Analysis was performed on language samples from 29 speakers with semantic variant PPA (svPPA), 25 speakers with logopenic variant PPA (lvPPA), 34 speakers with non-fluent variant PPA (nfvPPA), 14 speakers with behavioral variant FTD (bvFTD) and 20 older normal controls (NCs). We used frequency and collocation strength measures to determine use of familiar words and word combinations. We also computed word counts, content word ratio and a combination ratio, a measure of the degree to which the individual produces connected language. All dementia subtypes differed significantly from NCs. The most discriminating variables were word count, combination ratio, and content word ratio, each of which distinguished at least one dementia group from NCs. All participants with PPA, but not participants with bvFTD, produced significantly more frequent forms at the level of content words, word combinations, or both. Each dementia group differed from the others on at least one variable, and language production variables correlated with established behavioral measures of disease progression. A machine learning classifier, using narrative speech variables, achieved 90% accuracy when classifying samples as NC or dementia, and 59.4% accuracy when matching samples to their diagnostic group. Automated quantification of spontaneous speech in both language-led and non-language led dementias, is feasible. It allows extraction of syndromic profiles that complement those derived from standardized tests, warranting further evaluation as candidate biomarkers. Inclusion of frequency-based language variables benefits profiling and classification.

Writing errors in primary progressive aphasia

Peripheral errors in writing, that is errors produced download the spelling, have been occasionally described in primary progressive aphasia (PPA), but the possibility that these errors might be a marker of parkinsonism associated to some subtypes of PPA has not been explored. We investigated whether errors of peripheral nature characterize the writing disorder in PPA when associated with parkinsonian signs (PSs). Subgroups of PPA without PSs and with PSs were studied. The proportion of the central and peripheral errors in writing words and pseudowords was calculated in each group. In writing words, central errors significantly exceeded peripheral errors in subgroups without PSs. The higher the number of peripheral errors, the higher the probability of presenting PSs. No relation emerged between any error and the Unified Parkinson’s Disease Rating Scale, but both types of errors correlated with measures of cognitive ability. Peripheral errors emerge when PSs are associated with PPA and may be linked to a decay of the cognitive control on movement, possibly involving the right hemisphere. Peripheral errors have clinical relevance in PPA, to the extent that they may assume the significance of a marker of specific subtypes and can help to outline the specific clinical picture of individual patients.

Apathy and its impact on carer burden and psychological wellbeing in primary progressive aphasia

ObjectiveWhile patients with primary progressive aphasia (PPA) typically present with predominant language impairment, behavioural symptoms, such as apathy, are often under-recognised. We aimed to systematically characterise apathy across the three recognised subtypes of PPA, plus atypical right-lateralised presentations of semantic dementia, and to evaluate the impact of apathy on carer burden and psychological wellbeing. MethodsBaseline assessments from 114 PPA patients were included: 31 left semantic dementia (left SD) 16 right semantic dementia (right SD), 30 progressive nonfluent aphasia (PNFA) and 37 logopenic progressive aphasia (LPA). Clinician (Neuropsychiatric Inventory; NPI) and carer rated (Cambridge Behavioural Inventory; CBI, Frontal Systems Behaviour Scale; FrSBe) measures were used to quantify symptoms of apathy, and carer burden and psychological wellbeing were determined using the Zarit Burden Interview and Depression, Anxiety and Stress Scale. ResultsOn the NPI, symptoms of apathy were present in 39% left SD, 56% right SD, 33% PNFA and 43% LPA patients. Multiple regression analysis revealed that 17.9% of the variance in carer burden was uniquely explained by scores on carer rated measures of apathy (CBI, FrSBe), even after accounting for diagnosis, disease duration, and cognitive and language impairment. ConclusionsApathy is much more common than current diagnostic criteria for PPA would suggest, though the severity of apathy is similar across patient groups. Increased awareness and routine assessments of apathy symptoms are needed, together with targeted pharmacological and behavioural interventions. Moreover, as apathy substantially contributes to carer burden in PPA, psychoeducation addressing behavioural symptoms may be beneficial.

Impaired phonemic discrimination in logopenic variant primary progressive aphasia.

Logopenic variant primary progressive aphasia (lvPPA) is the least well defined of the major primary progressive aphasia (PPA) syndromes. We assessed phoneme discrimination in patients with PPA (semantic, nonfluent/agrammatic, and logopenic variants) and typical Alzheimer’s disease, relative to healthy age‐matched participants. The lvPPA group performed significantly worse than all other groups apart from tAD, after adjusting for auditory verbal working memory. In the combined PPA cohort, voxel‐based morphometry correlated phonemic discrimination score with grey matter in left angular gyrus. Our findings suggest that impaired phonemic discrimination may help differentiate lvPPA from other PPA subtypes, with important diagnostic and management implications.

Classification of primary progressive aphasia: challenges and complexities.

Primary progressive aphasia (PPA) is classified into three variants, logopenic variant PPA (lvPPA), nonfluent agrammatic PPA (nfaPPA), and semantic variant PPA (svPPA), based on clinical (syndromic) characteristics with support from neuroimaging and/or underlying neuropathology. Classification of PPA variants provides information valuable to disease management. International consensus criteria are widely employed to identify PPA subtypes; however, classification is complex, and some individuals do not fit neatly into the subtyping scheme. In this review, diagnostic challenges and their implications are discussed, possible explanations for these challenges are explored, and approaches to address PPA classification are considered.

Primary Progressive Aphasia: Diagnosis and Contribution of Graphic Markers

Primary Progressive Aphasia (PPA) is a neurodegenerative disease characterized by a foreground linguistic deficit that extends to other cognitive functions. Structural and cognitive impairments depend of the PPA subtype. Different pathological causes can lead to PPA, such as frontotemporal dementia (FTD) or Alzheimer disease (AD). An early differential diagnosis between the different aetiologies seems crucial to set up an appropriate care but remains difficult to make, according to the several diagnosis changes that can occur. Moreover, non-pharmacological interventions such as speech therapy have proven their usefulness in compensating and maintaining functional communication and the use of graphical parameters have shown a significant handwriting difference between several diseases such as Alzheimer’s disease (AD) or Parkinson’s disease (PD).

Caracterización del lenguaje en las variantes lingüísticas de la Afasia Progresiva Primaria

La Afasia Progresiva Primaria (APP) incluye a un conjunto de trastornos neurocognitivos con una afectación principal de la función lingüística. Se caracteriza por la preservación inicial del funcionamiento en las otras áreas cognitivas, mientras se va deteriorando la autonomía del individuo de forma significativa (Mesulam, 2016). Los recientes avances en neuroimagen y hallazgo de biomarcadores han contribuido a un mejor conocimiento de estos síndromes, aunque han generado a su vez la necesidad de revisar los criterios diagnósticos y la configuración clínica de sus variantes, con un resultado no exento de controversias. El objetivo de este trabajo es describir los síntomas del lenguaje que caracterizan a los distintos subtipos de APP, describiendo los criterios actualizados para su diagnóstico y las recientes clasificaciones de este grupo de patologías. En primer lugar, se presenta la ‘APP-variante no fluente’ o ‘agramática’, caracterizada por anormalidades en un tipo de discurso que resulta forzado, lento y telegráfico, concomitante con apraxia del habla o disartria. En segundo lugar, se describe la ‘APP-variante semántica’, caracterizada por un discurso fluido pero vacío de contenido, con uso de palabras genéricas y una relativa anomia. Por último, se analiza la ‘APP-variante logopénica’, caracterizada por la presencia de frecuentes pausas en el discurso y circunloquios originados por la dificultad mnésica para encontrar las palabras, con una relativa conservación de la gramática, en un perfil de deterioro lingüístico muy similar al de la Enfermedad de Alzheimer.

Profil jezičkih i kognitivnih deficita kod osoba sa semantičkom varijantom primarne progresivne afazije

Primary progressive aphasia (PPA) includes a group of neurodegenerative disorders that are characterized by progressive deterioration of language functions, while other cognitive functions, at least at the onset of the disease, are relatively spared. There are three basic subtypes of PPA: the nonfluent progressive aphasia (nvPPA), the semantic variant of a primary progressive aphasia (svPPA), and the logopenic progressive aphasia (lvPPA). The semantic variant of a PPA can also be found in the literature under the term of semantic dementia. It is clinically manifested by progressive deterioration of semantic knowledge, fluent aphasia, impaired naming and comprehension, prosopagnosia and surface dyslexia and dysgraphia (in languages with irregular orthography). As the disease progresses, other cognitive changes can be observed. The main cause of the disorder is progressive bilateral atrophy of the anterior temporal lobes, which is more manifested in the left hemisphere. The literature is modest in terms of the use of specific treatment methods in the rehabilitation of these patients. Since speech and language disorders are the most conspicuous symptom, at least at the beginning of the disease, the role of speech therapists in the assessment and restitution of speechlanguage and communication skills is also indisputable.

Multivariate analysis reveals anatomical correlates of naming errors in primary progressive aphasia

Primary progressive aphasia (PPA) is an overarching term for a heterogeneous group of neurodegenerative diseases which affect language processing. Impaired picture naming has been linked to atrophy of the anterior temporal lobe in the semantic variant of PPA. Although atrophy of the anterior temporal lobe proposedly impairs picture naming by undermining access to semantic knowledge, picture naming also entails object recognition and lexical retrieval. Using multivariate analysis, we investigated whether cortical atrophy relates to different types of naming errors generated during picture naming in 43 PPA patients (13 semantic, 9 logopenic, 11 nonfluent, and 10 mixed variant). Omissions were associated with atrophy of the anterior temporal lobes. Semantic errors, for example, mistaking a rhinoceros for a hippopotamus, were associated with atrophy of the left mid and posterior fusiform cortex and the posterior middle and inferior temporal gyrus. Semantic errors and atrophy in these regions occurred in each PPA subtype, without major between-subtype differences. We propose that pathological changes to neural mechanisms associated with semantic errors occur across the PPA spectrum.

Plasma Neurofilament Light Chain in Primary Progressive Aphasia and Related Disorders: Clinical Significance and Metabolic Correlates.

Primary progressive aphasia (PPA) is a heterogeneous syndrome that is difficult to diagnose at early stages. Plasma neurofilament light chain (NFL) has been proposed as a potential biomarker for PPA. To examine the diagnostic properties of plasma NFL in PPA and to evaluate its association with clinical stages of the disease and brain metabolism. Our study included 80 participants (13 with non-fluent, 12 with semantic, and 16 with logopenic variant PPA; 13 with amnestic Alzheimer's disease [AD]; 13 with behavioral variant frontotemporal dementia; and 13 healthy controls). Plasma NFL concentration was measured using a high-sensitivity enzyme-linked immunosorbent assay (ELISA) kit. PET imaging was performed in a subgroup of patients. NFL discriminated patients from controls with an area under the curve of 0.914 (95% CI, 0.843-0.984; p < 0.001) (cut-off: 76.46 pg/mL; 94% sensitivity, 76.9% specificity). There were no significant differences between clinical syndromes (PPA subtypes), the main clinical forms of dementia (frontotemporal dementia and AD), or the expected pathological groups (frontotemporal lobar degeneration-tau [FTLD-tau], FTLD-TDP43, and AD). NFL levels showed weak to moderate correlations with age and functional scale score. We found no significant correlation with the extent of hypometabolism observed on FDG-PET images. Plasma NFL is a non-specific marker of neurodegeneration, and may be helpful in the diagnosis of PPA. However, NFL does not permit differential diagnosis between PPA subtypes and is not correlated with the extent of neurodegeneration.

APOE is a correlate of phenotypic heterogeneity in Alzheimer disease in a national cohort.

To compare the proportion of APOE ε4 genotype carriers in aphasic vs amnestic variants of Alzheimer disease (AD). The proportion of APOE ε4 carriers was compared among the following 3 groups: (1) 42 patients with primary progressive aphasia (PPA) and AD pathology (PPA/AD) enrolled in the Northwestern Alzheimer Disease Center Clinical Core; (2) 1,418 patients with autopsy-confirmed AD and amnestic dementia of the Alzheimer type (DAT/AD); and (3) 2,608 cognitively normal controls (NC). The latter 2 groups were compiled from the National Alzheimer Coordinating Center database. Logistic regression models analyzed the relationship between groups and APOE ε4 carrier status, adjusting for age at onset and sex as needed. Using NC as the reference and adjusting for sex and age, the DAT/AD group was 3.97 times more likely to be APOE ε4 carriers. Adjusting for sex and age at symptom onset, the DAT/AD group was 2.46 times as likely to be carriers compared to PPA/AD. There was no significant difference in the proportion of APOE ε4 carriers for PPA/AD compared to NC. PPA subtypes included 24 logopenic, 10 agrammatic nonfluent, and 8 either mixed (n = 5) or too severe (n = 3) to subtype. The proportion of carriers and noncarriers was similar for logopenic and agrammatic subtypes, both having fewer carriers. The proportion of APOE ε4 carriers was elevated in amnestic but not aphasic manifestations of AD. These results suggest that APOE ε4 is an anatomically selective risk factor that preferentially increases the vulnerability to AD pathology of memory-related medial temporal areas rather than language-related neocortices.

Treatment for Word Retrieval in Semantic and Logopenic Variants of Primary Progressive Aphasia: Immediate and Long-Term Outcomes

Purpose Recent studies confirm the utility of speech-language intervention in primary progressive aphasia (PPA); however, long-term outcomes, ideal dosage parameters, and relative benefits of intervention across clinical variants warrant additional investigation. The purpose of this study was to determine whether naming treatment affords significant, lasting, and generalized improvement for individuals with semantic and logopenic PPA and whether dosage manipulations significantly affect treatment outcomes. Method Eighteen individuals with PPA (9 semantic and 9 logopenic variant) underwent lexical retrieval treatment designed to leverage spared cognitive-linguistic domains and develop self-cueing strategies to promote naming. One group (n = 10) underwent once-weekly treatment sessions, and the other group (n = 8) received the same treatment with 2 sessions per week and an additional "booster" treatment phase at 3 months post-treatment. Performance on trained and untrained targets/tasks was measured immediately after treatment and at 3, 6, and 12 months post-treatment. Results Outcomes from the full cohort of individuals with PPA showed significantly improved naming of trained items immediately post-treatment and at all follow-up assessments through 1 year. Generalized improvement on untrained items was significant up to 6 months post-treatment. The positive response to treatment was comparable regardless of session frequency or inclusion of a booster phase. Outcomes were comparable across PPA subtypes, as was maintenance of gains over the post-treatment period. Conclusion This study documents positive naming treatment outcomes for a group of individuals with PPA, demonstrating strong direct treatment effects, maintenance of gains up to 1 year post-treatment, and generalization to untrained items. Lexical retrieval treatment, in conjunction with daily home practice, had a strong positive effect that did not require more than 1 clinician-directed treatment session per week. Findings confirm that strategic training designed to capitalize on spared cognitive-linguistic abilities results in significant and lasting improvement, despite ongoing disease progression, in PPA.

Distinguishing logopenic from semantic & nonfluent variant primary progressive aphasia: Patterns of linguistic and behavioral correlations

ABSTRACTWhile language characteristics of logopenic variant primary progressive aphasia (lvPPA) are well-defined, behavioral characteristics are less understood. We investigated correlations between language and behavioral scores across three variants of primary progressive aphasia (PPA) and found language performance and behavioral disturbances are correlated in lvPPA, but not other PPA subtypes. Results suggest that unlike other PPA variants, patients diagnosed with lvPPA do not develop negative behaviors until language deficits are severe. This is consistent with the underlying neuropathology of lvPPA, Alzheimer's Disease. Such findings are crucial to clinical prognosis, especially when considering the progressive nature of this disease.

Characterization of language features of subtypes of primary progressive aphasia based on clustering analysis of brain metabolism (P3.1-002)

Characterization of language features of subtypes of primary progressive aphasia based on clustering analysis of brain metabolism (P3.1-002)

Quantification of motor speech impairment and its anatomic basis in primary progressive aphasia

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.

Relationships between [¹⁸F]-THK5351 Retention and Language Functions in Primary Progressive Aphasia.

Background and PurposeThere are three distinct subtypes of primary progressive aphasia (PPA): the nonfluent/agrammatic variant (nfvPPA), the semantic variant (svPPA), and the logopenic variant (lvPPA). We sought to characterize the pattern of [18F]-THK5351 retention across all three subtypes and determine the topography of [18F]-THK5351 retention correlated with each neurolinguistic score.MethodsWe enrolled 50 participants, comprising 13 PPA patients (3 nfvPPA, 5 svPPA, and 5 lvPPA) and 37 subjects with normal cognition (NC) who underwent 3.0-tesla magnetic resonance imaging, [18F]-THK5351 positron-emission tomography scans, and detailed neuropsychological tests. The PPA patients additionally participated in extensive neurolinguistic tests. Voxel-wise and region-of-interest-based analyses were performed to analyze [18F]-THK5351 retention.ResultsThe nfvPPA patients exhibited higher [18F]-THK5351 retention in the the left inferior frontal and precentral gyri. In svPPA patients, [18F]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared to the NC group (left>right). The lvPPA patients exhibited predominant [18F]-THK5351 retention in the inferior parietal, lateral temporal, and dorsolateral prefrontal cortices, and the precuneus (left>right). [18F]-THK5351 retention in the left inferior frontal area was associated with lower fluency scores. Comprehension was correlated with [18F]-THK5351 retention in the left temporal cortices. Repetition was associated with [18F]-THK5351 retention in the left inferior parietal and posterior temporal areas, while naming difficulty was correlated with retention in the left fusiform and temporal cortices.ConclusionsThe pattern of [18F]-THK5351 retention was well matched with clinical and radiological findings for each PPA subtype, in agreement with the anatomical and functional location of each language domain.

Primary Progressive Aphasia: Natural History in an Italian Cohort.

Few longitudinal studies have explored the progression of cognitive and functional impairment of patients with primary progressive aphasia (PPA). The aims of the study were to describe the clinical, neuroimaging, and genetic features of a cohort of 68 PPA patients, and to outline the natural history of the disease. A sample of 23 patients with the logopenic variant, 26 with the nonfluent/agrammatic variant, and 19 with the semantic variant was retrospectively collected and followed-up for a maximum of 6 years. Clinical-neuropsychological assessment, fluorodeoxyglucose positron emission tomographic imaging, and genetic analyses were acquired at baseline. Disease progression was evaluated in terms of language impairment, global cognitive decline, and functional dependency. During follow-up, one third of subjects presented total language loss, and 20% severe functional dependency. Global cognitive decline after the first year (hazard ratio, 5.93; confidence interval, 1.63-21.56) and high schooling (hazard ratio, 0.07; confidence interval, 0.008-0.74) represented risk factors for functional impairment. The apolipoprotein E status was associated with the progression of cognitive decline. Positive family history for dementia was frequent and 3 genetic autosomal dominant mutations were identified. There were no differences in the progression of PPA subtypes. Genetics plays an important role in disease onset and progression.