Written Language Impairments in Primary Progressive Aphasia: A Reflection of Damage to Central Semantic and Phonological Processes

Connectionist theories of language propose that written language deficits arise as a result of damage to semantic and phonological systems that also support spoken language production and comprehension, a view referred to as the “primary systems” hypothesis. The objective of the current study was to evaluate the primary systems account in a mixed group of individuals with primary progressive aphasia (PPA) by investigating the relation between measures of nonorthographic semantic and phonological processing and written language performance and by examining whether common patterns of cortical atrophy underlie impairments in spoken versus written language domains. Individuals with PPA and healthy controls were administered a language battery, including assessments of semantics, phonology, reading, and spelling. Voxel-based morphometry was used to examine the relation between gray matter volumes and language measures within brain regions previously implicated in semantic and phonological processing. In accordance with the primary systems account, our findings indicate that spoken language performance is strongly predictive of reading/spelling profile in individuals with PPA and suggest that common networks of critical left hemisphere regions support central semantic and phonological processes recruited for spoken and written language.

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Clinical Characteristic in Primary Progressive Aphasia in Relation to Alzheimer’s Disease Biomarkers

Journal of Alzheimer s Disease ◽

10.3233/jad-210392 ◽

2021 ◽

pp. 1-13

Author(s):

Sung Hoon Kang ◽

Hanna Cho ◽

Jiho Shin ◽

Hang-Rai Kim ◽

Young Noh ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Language Impairment ◽

Amyloid Β ◽

Primary Progressive Aphasia ◽

Cortical Atrophy ◽

Clinical Feature ◽

Progressive Aphasia ◽

Disease Biomarkers ◽

Primary Progressive

Background: Primary progressive aphasia (PPA) is associated with amyloid-β (Aβ) pathology. However, clinical feature of PPA based on Aβ positivity remains unclear. Objective: We aimed to assess the prevalence of Aβ positivity in patients with PPA and compare the clinical characteristics of patients with Aβ-positive (A+) and Aβ-negative (A–) PPA. Further, we applied Aβ and tau classification system (AT system) in patients with PPA for whom additional information of in vivo tau biomarker was available. Methods: We recruited 110 patients with PPA (41 semantic [svPPA], 27 non-fluent [nfvPPA], 32 logopenic [lvPPA], and 10 unclassified [ucPPA]) who underwent Aβ-PET imaging at multi centers. The extent of language impairment and cortical atrophy were compared between the A+ and A–PPA subgroups using general linear models. Results: The prevalence of Aβ positivity was highest in patients with lvPPA (81.3%), followed by ucPPA (60.0%), nfvPPA (18.5%), and svPPA (9.8%). The A+ PPA subgroup manifested cortical atrophy mainly in the left superior temporal/inferior parietal regions and had lower repetition scores compared to the A–PPA subgroup. Further, we observed that more than 90%(13/14) of the patients with A+ PPA had tau deposition. Conclusion: Our findings will help clinicians understand the patterns of language impairment and cortical atrophy in patients with PPA based on Aβ deposition. Considering that most of the A+ PPA patents are tau positive, understanding the influence of Alzheimer’s disease biomarkers on PPA might provide an opportunity for these patients to participate in clinical trials aimed for treating atypical Alzheimer’s disease.

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A Case of a Monolingual Spanish-Speaking Latina with Semantic Variant Primary Progressive Aphasia (svPPA)

Archives of Clinical Neuropsychology ◽

10.1093/arclin/acz029.57 ◽

2019 ◽

Vol 34 (7) ◽

pp. 1290-1290

Author(s):

L Perez

Keyword(s):

Working Memory ◽

Language Production ◽

Primary Progressive Aphasia ◽

Motor Speech ◽

Problem Solving Skills ◽

Progressive Aphasia ◽

Primary Progressive ◽

Spanish Speaking ◽

Word Finding ◽

Semantic Variant

Abstract Objective Often, individuals with lower educational attainment and limited proficiency in the English language get misdiagnosed and/or undertreated, which can impact their quality of life and other outcomes. The present case study intends to review and discuss the presentation of a monolingual, Spanish-speaking woman with Semantic Variant Primary Progressive Aphasia (svPPA), who was originally referred for a neuropsychological evaluation to determine the severity of her existing Alzheimer’s Disease (AD) diagnosis. Case Description Ms. X, is a 64-year-old, right-handed Hispanic woman with 6 years of education. Symptoms included forgetfulness, restlessness, and insomnia. Her family reported that she was repeating her ideas frequently during conversations and failing to recognize previously acquainted people, including her own relatives. A recent MRI of the brain showed anterior temporal lobe atrophy. Diagnostic Impressions and Outcomes Overall, she showed naming deficits (anomia), impaired verbal fluency, surface dyslexia, and significant problems with comprehension. Executive functioning, sentence repetition, working memory, and attention were generally intact. Qualitatively, her speech was apparently fluent and automatic, yet clearly empty in meaning. In Ms. X’s case, collateral reports of word-finding difficulties, tendency to repeat her thoughts incessantly, associative agnosia and prosopagnosia, and spared repetition and motor speech are strongly indicative of svPPA. Discussion svPPA primarily impacts language production and comprehension, and is characterized by severe anomia, word-finding difficulties, impaired single word comprehension, and in some cases, defective recognition of familiar faces. On testing, impairments can be observed in confrontation naming, with motor speech and repetition, working memory, episodic memory, visuospatial skills, and problem-solving skills relatively intact. Language symptoms are thought to stem from deficits of the semantic system.

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Asymmetric TDP pathology in primary progressive aphasia with right hemisphere language dominance

Neurology ◽

10.1212/wnl.0000000000004891 ◽

2018 ◽

Vol 90 (5) ◽

pp. e396-e403 ◽

Cited By ~ 6

Author(s):

Garam Kim ◽

Shahrooz Vahedi ◽

Tamar Gefen ◽

Sandra Weintraub ◽

Eileen H. Bigio ◽

...

Keyword(s):

Right Hemisphere ◽

Primary Progressive Aphasia ◽

Cortical Atrophy ◽

Progressive Aphasia ◽

Language Dominance ◽

Primary Progressive ◽

Activated Microglia ◽

Unbiased Stereology ◽

Cortical Regions ◽

The Right

ObjectiveTo quantitatively examine the regional densities and hemispheric distribution of the 43-kDa transactive response DNA-binding protein (TDP-43) inclusions, neurons, and activated microglia in a left-handed patient with right hemisphere language dominance and logopenic-variant primary progressive aphasia (PPA).MethodsPhosphorylated TDP-43 inclusions, neurons, and activated microglia were visualized with immunohistochemical and histologic methods. Markers were quantified bilaterally with unbiased stereology in language- and memory-related cortical regions.ResultsClinical MRI indicated cortical atrophy in the right hemisphere, mostly in the temporal lobe. Significantly higher densities of TDP-43 inclusions were present in right language-related temporal regions compared to the left or to other right hemisphere regions. The memory-related entorhinal cortex (ERC) and language regions without significant atrophy showed no asymmetry. Activated microglia displayed extensive asymmetry (R > L). A substantial density of neurons remained in all areas and showed no hemispheric asymmetry. However, perikaryal size was significantly smaller in the right hemisphere across all regions except the ERC. To demonstrate the specificity of this finding, sizes of residual neurons were measured in a right-handed case with PPA and were found to be smaller in the language-dominant left hemisphere.ConclusionsThe distribution of TDP-43 inclusions and microglial activation in right temporal language regions showed concordance with anatomic distribution of cortical atrophy and clinical presentation. The results revealed no direct relationship between density of TDP-43 inclusions and activated microglia. Reduced size of the remaining neurons is likely to contribute to cortical atrophy detected by MRI. These findings support the conclusion that there is no obligatory relationship between logopenic PPA and Alzheimer pathology.

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Prominent microglial activation in cortical white matter is selectively associated with cortical atrophy in primary progressive aphasia

Neuropathology and Applied Neurobiology ◽

10.1111/nan.12494 ◽

2018 ◽

Vol 45 (3) ◽

pp. 216-229 ◽

Cited By ~ 7

Author(s):

D. T. Ohm ◽

G. Kim ◽

T. Gefen ◽

A. Rademaker ◽

S. Weintraub ◽

...

Keyword(s):

White Matter ◽

Microglial Activation ◽

Primary Progressive Aphasia ◽

Cortical Atrophy ◽

Progressive Aphasia ◽

Primary Progressive

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PROMINENT MICROGLIAL ACTIVATION IN CORTICAL WHITE MATTER IS SELECTIVELY ASSOCIATED WITH CORTICAL ATROPHY IN PRIMARY PROGRESSIVE APHASIA

Alzheimer s & Dementia ◽

10.1016/j.jalz.2017.07.596 ◽

2017 ◽

Vol 13 (7) ◽

pp. P1499

Author(s):

Daniel T. Ohm ◽

Garam Kim ◽

Tamar Gefen ◽

Alfred Rademaker ◽

Sandra Weintraub ◽

...

Keyword(s):

White Matter ◽

Microglial Activation ◽

Primary Progressive Aphasia ◽

Cortical Atrophy ◽

Progressive Aphasia ◽

Primary Progressive

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Phonological Processing in Primary Progressive Aphasia

Journal of Cognitive Neuroscience ◽

10.1162/jocn_a_00901 ◽

2016 ◽

Vol 28 (2) ◽

pp. 210-222 ◽

Cited By ~ 29

Author(s):

Maya L. Henry ◽

Stephen M. Wilson ◽

Miranda C. Babiak ◽

Maria Luisa Mandelli ◽

Pelagie M. Beeson ◽

...

Keyword(s):

Language Processing ◽

Phonological Processing ◽

Critical Role ◽

Dorsal Stream ◽

Primary Progressive Aphasia ◽

Binary Logistic Regression ◽

Progressive Aphasia ◽

Primary Progressive ◽

Dorsal Pathway ◽

High Degree

Individuals with primary progressive aphasia (PPA) show selective breakdown in regions within the proposed dorsal (articulatory–phonological) and ventral (lexical–semantic) pathways involved in language processing. Phonological STM impairment, which has been attributed to selective damage to dorsal pathway structures, is considered to be a distinctive feature of the logopenic variant of PPA. By contrast, phonological abilities are considered to be relatively spared in the semantic variant and are largely unexplored in the nonfluent/agrammatic variant. Comprehensive assessment of phonological ability in the three variants of PPA has not been undertaken. We investigated phonological processing skills in a group of participants with PPA as well as healthy controls, with the goal of identifying whether patterns of performance support the dorsal versus ventral functional–anatomical framework and to discern whether phonological ability differs among PPA subtypes. We also explored the neural bases of phonological performance using voxel-based morphometry. Phonological performance was impaired in patients with damage to dorsal pathway structures (nonfluent/agrammatic and logopenic variants), with logopenic participants demonstrating particular difficulty on tasks involving nonwords. Binary logistic regression revealed that select phonological tasks predicted diagnostic group membership in the less fluent variants of PPA with a high degree of accuracy, particularly in conjunction with a motor speech measure. Brain–behavior correlations indicated a significant association between the integrity of gray matter in frontal and temporoparietal regions of the left hemisphere and phonological skill. Findings confirm the critical role of dorsal stream structures in phonological processing and demonstrate unique patterns of impaired phonological processing in logopenic and nonfluent/agrammatic variants of PPA.

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Dissolution of spoken language in primary progressive aphasia

Aphasiology ◽

10.1080/02687039808249563 ◽

1998 ◽

Vol 12 (7-8) ◽

pp. 635-650 ◽

Cited By ~ 28

Author(s):

Margaret A. Rogers ◽

Nancy B. Alarcon

Keyword(s):

Primary Progressive Aphasia ◽

Spoken Language ◽

Progressive Aphasia ◽

Primary Progressive

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Quantitative Analysis of Agrammatism in Agrammatic Primary Progressive Aphasia and Dominant Apraxia of Speech

Journal of Speech Language and Hearing Research ◽

10.1044/2018_jslhr-l-17-0474 ◽

2018 ◽

Vol 61 (9) ◽

pp. 2337-2346 ◽

Cited By ~ 3

Author(s):

Katerina A. Tetzloff ◽

Rene L. Utianski ◽

Joseph R. Duffy ◽

Heather M. Clark ◽

Edythe A. Strand ◽

...

Keyword(s):

Language Production ◽

Primary Progressive Aphasia ◽

Broca’S Area ◽

Apraxia Of Speech ◽

Broca's Area ◽

Progressive Aphasia ◽

Primary Progressive ◽

Semantic Errors ◽

Description Task ◽

Mean Length Of Utterance

Purpose The aims of the study were to assess and compare grammatical deficits in written and spoken language production in subjects with agrammatic primary progressive aphasia (agPPA) and in subjects with agrammatism in the context of dominant apraxia of speech (DAOS) and to investigate neuroanatomical correlates. Method Eight agPPA and 21 DAOS subjects performed the picture description task of the Western Aphasia Battery (WAB) both in writing and orally. Responses were transcribed and coded for linguistic analysis. agPPA and DAOS were compared to 13 subjects with primary progressive apraxia of speech (PPAOS) who did not have agrammatism. Spearman correlations were performed between the written and spoken variables. Patterns of atrophy in each group were compared, and relationships between the different linguistic measures and integrity of Broca's area were assessed. Results agPPA and DAOS both showed lower mean length of utterance, fewer grammatical utterances, more nonutterances, more syntactic and semantic errors, and fewer complex utterances than PPAOS in writing and speech, as well as fewer correct verbs and nouns in speech. Only verb ratio and proportion of grammatical utterances correlated between modalities. agPPA and DAOS both showed greater involvement of Broca's area than PPAOS, and atrophy of Broca's area correlated with proportion of grammatical and ungrammatical utterances and semantic errors in writing and speech. Conclusions agPPA and DAOS subjects showed similar patterns of agrammatism, although subjects performed differently when speaking versus writing. Integrity of Broca's area correlates with agrammatism.

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