RESUMO
Phonemic paraphasias are thought to reflect phonological (post-semantic) deficits in language production. Here we present evidence that phonemic paraphasias in non-semantic primary progressive aphasia (PPA) may be associated with taxonomic interference. Agrammatic and logopenic PPA patients and control participants performed a word-to-picture visual search task where they matched a stimulus noun to 1 of 16 object pictures as their eye movements were recorded. Participants were subsequently asked to name the same items. We measured taxonomic interference (ratio of time spent viewing related vs. unrelated foils) during the search task for each item. Target items that elicited a phonemic paraphasia during object naming elicited increased taxonomic interference during the search task in agrammatic but not logopenic PPA patients. These results could reflect either very subtle sub-clinical semantic distortions of word representations or partial degradation of specific phonological word forms in agrammatic PPA during both word-to-picture matching (input stage) and picture naming (output stage). The mechanism for phonemic paraphasias in logopenic patients seems to be different and to be operative at the pre-articulatory stage of phonological retrieval. Glucose metabolic imaging suggests that degeneration in the left posterior frontal lobe and left temporo-parietal junction, respectively, might underlie these different patterns of phonemic paraphasia.
Assuntos
Afasia Primária Progressiva/diagnóstico por imagem , Afasia Primária Progressiva/metabolismo , Fonética , Desempenho Psicomotor/classificação , Semântica , Idoso , Afasia Primária Progressiva/psicologia , Movimentos Oculares/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estimulação Luminosa/métodos , Tomografia por Emissão de Pósitrons/métodos , Desempenho Psicomotor/fisiologiaRESUMO
AIMS: Primary progressive aphasia (PPA) is a clinical syndrome characterized by selective language impairments associated with focal cortical atrophy favouring the language dominant hemisphere. PPA is associated with Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) and significant accumulation of activated microglia. Activated microglia can initiate an inflammatory cascade that may contribute to neurodegeneration, but their quantitative distribution in cortical white matter and their relationship with cortical atrophy remain unknown. We investigated white matter activated microglia and their association with grey matter atrophy in 10 PPA cases with either AD or FTLD-TDP pathology. METHODS: Activated microglia were quantified with optical density measures of HLA-DR immunoreactivity in two regions with peak cortical atrophy, and one nonatrophied region within the language dominant hemisphere of each PPA case. Nonatrophied contralateral homologues of the language dominant regions were examined for hemispheric asymmetry. RESULTS: Qualitatively, greater densities of activated microglia were observed in cortical white matter when compared to grey matter. Quantitative analyses revealed significantly greater densities of activated microglia in the white matter of atrophied regions compared to nonatrophied regions in the language dominant hemisphere (P < 0.05). Atrophied regions of the language dominant hemisphere also showed significantly more activated microglia compared to contralateral homologues (P < 0.05). CONCLUSIONS: White matter activated microglia accumulate more in atrophied regions in the language dominant hemisphere of PPA. While microglial activation may constitute a response to neurodegenerative processes in white matter, the resultant inflammatory processes may also exacerbate disease progression and contribute to cortical atrophy.
Assuntos
Doença de Alzheimer , Afasia Primária Progressiva , Córtex Cerebral , Demência Frontotemporal , Substância Cinzenta , Microglia/imunologia , Substância Branca , Idoso , Doença de Alzheimer/imunologia , Doença de Alzheimer/patologia , Afasia Primária Progressiva/imunologia , Afasia Primária Progressiva/patologia , Atrofia/imunologia , Atrofia/patologia , Córtex Cerebral/imunologia , Córtex Cerebral/patologia , Feminino , Demência Frontotemporal/imunologia , Demência Frontotemporal/patologia , Substância Cinzenta/imunologia , Substância Cinzenta/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Substância Branca/imunologia , Substância Branca/patologiaRESUMO
Though it may seem simple, object naming is a complex multistage process that can be impaired by lesions at various sites of the language network. Individuals with neurodegenerative disorders of language, known as primary progressive aphasias (PPA), have difficulty with naming objects, and instead frequently say "I don't know" or fail to give a vocal response at all, known as an omission. Whereas other types of naming errors (paraphasias) give clues as to which aspects of the language network have been compromised, the mechanisms underlying omissions remain largely unknown. In this study, we used a novel eye tracking approach to probe the cognitive mechanisms of omissions in the logopenic and semantic variants of PPA (PPA-L and PPA-S). For each participant, we identified pictures of common objects (e.g., animals, tools) that they could name aloud correctly, as well as pictures that elicited an omission. In a separate word-to-picture matching task, those pictures appeared as targets embedded among an array with 15 foils. Participants were given a verbal cue and tasked with pointing to the target, while eye movements were monitored. On trials with correctly-named targets, controls and both PPA groups ceased visual search soon after foveating the target. On omission trials, however, the PPA-S group failed to stop searching, and went on to view many foils "post-target". As further indication of impaired word knowledge, gaze of the PPA-S group was subject to excessive "taxonomic capture", such that they spent less time viewing the target and more time viewing related foils on omission trials. In contrast, viewing behavior of the PPA-L group was similar to controls on both correctly-named and omission trials. These results indicate that the mechanisms of omission in PPA differ by variant. In PPA-S, anterior temporal lobe degeneration causes taxonomic blurring, such that words from the same category can no longer be reliably distinguished. In PPA-L, word knowledge remains relatively intact, and omissions instead appear to be caused by downstream factors (e.g., lexical access, phonological encoding). These findings demonstrate that when words fail, eye movements can be particularly informative.
Assuntos
Afasia Primária Progressiva , Movimentos Oculares , Humanos , Afasia Primária Progressiva/psicologia , Idioma , Semântica , Boca/patologiaRESUMO
Comparative studies on the presence and immunological reactivity of CEA and CEA-like antigens in lung and digestive tract cancers were performed. Specific goat and rabbit anti-CEA immune sera were used. Immunofluorescence studies revealed in histologically different types of the lung carcinomas the presence of the cross reacting antigen with classical CEA. Absorption procedures, and double diffusion tests have shown the existence of two at least antigenic determinants in CEA molecule: 1. the determinant specific for the lower parts of the digestive tract cancers not found in the lung carcinomas, and 2. the determinant common for the lung, and the digestive tract cancers.
Assuntos
Antígenos de Neoplasias , Antígeno Carcinoembrionário/imunologia , Neoplasias Pulmonares/imunologia , Adenocarcinoma/imunologia , Carcinoma de Células Escamosas/imunologia , Reações Cruzadas , Epitopos , Neoplasias Gastrointestinais/imunologia , Humanos , Metástase Linfática/imunologia , Sarcoma/imunologiaRESUMO
The axons in the parahippocampal white matter (PWM) region that includes the perforant pathway relay multimodal sensory information, important for memory function, from the entorhinal cortex to the hippocampus. Previous work suggests that the integrity of the PWM shows changes in individuals with amnestic mild cognitive impairment and is further compromised as Alzheimer's disease progresses. The present study was undertaken to determine the effects of healthy aging on macro- and micro-structural alterations in the PWM. The study characterized in vivo white matter changes in the parahippocampal region that includes the perforant pathway in cognitively healthy young (YNG, n=21) compared to cognitively healthy older (OLD, n=21) individuals using volumetry, diffusion tensor imaging (DTI) and tractography. Results demonstrated a significant reduction in PWM volume in old participants, with further indications of reduced integrity of remaining white matter fibers. In logistic regressions, PWM volume, memory performance and DTI indices of PWM integrity were significant indicator variables for differentiating the young and old participants. Taken together, these findings suggest that age-related alterations do occur in the PWM region and may contribute to the normal decline in memory function seen in healthy aging by degrading information flow to the hippocampus.
Assuntos
Envelhecimento/patologia , Transtornos da Memória/patologia , Memória , Fibras Nervosas Mielinizadas/patologia , Via Perfurante/patologia , Lobo Temporal/patologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Imagem de Tensor de Difusão , Feminino , Humanos , Modelos Logísticos , Masculino , Testes Neuropsicológicos , Tamanho do ÓrgãoRESUMO
OBJECTIVES: To examine the longitudinal course of primary progressive aphasia (PPA) over a 2-year period and to offer quantitative ranges of expected change that could be used to guide the design and evaluation of therapeutic intervention trials. METHODS: Regional changes of cortical thickness and whole-brain cortical volume loss as well as neuropsychological language performance were assessed at baseline and 2 years later in 13 rigorously characterized patients who fulfilled research criteria for logopenic, agrammatic, and semantic PPA subtypes (6 PPA-L, 3 PPA-G, and 4 PPA-S). RESULTS: There was substantial progression of clinical deficits and cortical atrophy over 2 years. Neuropsychological language performance patterns lost the sharp distinctions that differentiated one PPA variant from another. Nonetheless, the subtype-specific differential impairment of word comprehension vs grammatical processing was largely maintained. Peak atrophy sites spread beyond the initial distinctive locations that characterized each of the 3 subtypes and displayed a more convergent distribution encompassing all 3 major components of the language network: the inferior frontal gyrus, the temporoparietal junction, and lateral temporal cortex. Despite the progression, overall peak atrophy remained lateralized to the left hemisphere. CONCLUSIONS: The results suggest that the unique features, which sharply differentiate the PPA variants at the early to middle stages, may lose their distinctiveness as the degeneration becomes more severe. Given the substantial atrophy over 2 years, PPA clinical trials may require fewer patients and shorter study durations than Alzheimer disease trials to detect significant therapeutic effects.
Assuntos
Afasia Primária Progressiva/complicações , Afasia Primária Progressiva/patologia , Afasia Primária Progressiva/fisiopatologia , Progressão da Doença , Transtornos da Linguagem/etiologia , Transtornos da Linguagem/fisiopatologia , Idoso , Afasia Primária Progressiva/terapia , Ensaios Clínicos como Assunto , Humanos , Transtornos da Linguagem/terapia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Desempenho PsicomotorRESUMO
In the present study, as part of a more extensive longitudinal investigation of the in vivo anatomical markers of early and incipient AD in our laboratory, three groups of elderly participants were followed with yearly clinical evaluations and high resolution MRI scans over a 6-year period (baseline and 5 years of follow-up). At baseline, participants consisted of: (1) 35 old subjects with no cognitive impairment (controls); (2) 33 participants with amnestic mild cognitive impairment (MCI); and (3) 14 patients with very mild AD. 11 participants with amnestic MCI received a diagnosis of AD over the follow-up period and 9 controls declined in cognitive function. T1 weighted MRI scans were acquired using a 3D SPGR pulse sequence. At baseline, both the amnestic MCI and mild AD groups differed from the controls in hippocampal and entorhinal cortex volume, but not from each other. Longitudinal analyses showed that the rate of atrophy of the entorhinal cortex and hippocampus for the stable controls differed significantly from MCI participants who converted to AD and the AD groups. Furthermore, longitudinal decreases in hippocampal and entorhinal volume were related to longitudinal decline in declarative memory performance. These findings suggest that the rate of atrophy of mesial temporal lobe structures can differentiate healthy from pathological aging.
Assuntos
Doença de Alzheimer/diagnóstico , Doença de Alzheimer/patologia , Córtex Entorrinal/patologia , Hipocampo/patologia , Memória/fisiologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/psicologia , Atrofia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/patologia , Transtornos Cognitivos/psicologia , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Valor Preditivo dos TestesAssuntos
Cistos/complicações , Deficiência do Fator X/complicações , Transtornos Hemorrágicos/etiologia , Hipoprotrombinemias/complicações , Cisto Mediastínico/complicações , Cistos/cirurgia , Técnicas de Diagnóstico por Cirurgia , Deficiência do Fator X/genética , Feminino , Transtornos Hemorrágicos/genética , Humanos , Recém-Nascido , Cisto Mediastínico/cirurgia , Timo/cirurgiaAssuntos
Miastenia Gravis/terapia , Timectomia , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Timectomia/métodosAssuntos
Tumor do Corpo Carotídeo , Tumor do Corpo Carotídeo/cirurgia , Paraganglioma Extrassuprarrenal/cirurgia , Adulto , Idoso , Artérias Carótidas/diagnóstico por imagem , Tumor do Corpo Carotídeo/diagnóstico por imagem , Humanos , Masculino , Paraganglioma Extrassuprarrenal/diagnóstico por imagem , RadiografiaAssuntos
Drenagem/instrumentação , Pleura , Pneumotórax/cirurgia , Adolescente , Adulto , Feminino , Humanos , Masculino , Métodos , Pessoa de Meia-IdadeAssuntos
Neoplasias Pulmonares/cirurgia , Pulmão/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase NeoplásicaRESUMO
Primary Progressive Aphasia (PPA) is a neurodegenerative syndrome characterized by a gradual dissolution of language, but relative sparing of other cognitive domains during the initial stages of the disease. Research has led to substantial progress in understanding the clinical characteristics, genetics, and neuropathology of this syndrome. This article reviews the clinical criteria for diagnosing PPA, discusses the utility of defining the mild cognitive impairment (MCI) stage of PPA, and highlights some of the more recent research advances particularly in the area of pathology and genetics.