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Classification of primary progressive aphasia: do unsupervised data mining methods support a logopenic variant?
Publication . Maruta, Carolina; Pereira, Telma; Madeira, Sara C.; De Mendonça, Alexandre; Guerreiro, Manuela
Our objective was to test whether data mining techniques, through an unsupervised learning approach, support the three-group diagnostic model of primary progressive aphasia (PPA) versus the existence of two main/classic groups. A series of 155 PPA patients observed in a clinical setting and subjected to at least one neuropsychological/language assessment was studied. Several demographic, clinical and neuropsychological attributes, grouped in distinct sets, were introduced in unsupervised learning methods (Expectation Maximization, K-Means, X-Means, Hierarchical Clustering and Consensus Clustering). Results demonstrated that unsupervised learning methods revealed two main groups consistently obtained throughout all the analyses (with different algorithms and different set of attributes). One group included most of the agrammatic/non-fluent and some logopenic cases while the other was mainly composed of semantic and logopenic cases. Clustering the patients in a larger number of groups (k > 2) revealed some clusters composed mostly of non-fluent or of semantic cases. However, we could not evidence any group chiefly composed of logopenic cases. In conclusion, unsupervised data mining approaches do not support a clear distinction of logopenic PPA as a separate variant.
Primary progressive aphasia : neuropsychological analysis and evolution
Publication . Maruta, Carolina; Guerreiro, Manuela, 1952-; Mendonça, Alexandre de, 1958-
Frontotemporal lobar degeneration (FTLD) is the second leading cause of early-onset (< 65 years) dementia. Some of its forms may begin by isolated language deficits, which are known as Primary Progressive Aphasia (PPA). PPA is defined as the insidious onset and progressive loss of linguistic abilities in the absence of major deficits in other areas of cognition or in activities of daily living, which are not explained by a focal brain lesion. The most recent criteria and the increasing focus on the establishment of disease-modifying therapies in FTLD, which are presently lacking, highlight the importance of neuropsychology for an early and accurate diagnosis. In light of the new classification, understanding the neuropsychology of progressive aphasias may help to early differentiate disease patterns and predict their underlying pathology. This is particularly relevant since PPA is a language-based neurodegenerative disorder that evolves to a broader cognitive decline to the point where daily-living activities will also become compromised. Thus the main objective of the present thesis was to study the contribution of neuropsychology to the identification of different clinical profiles and defining features relevant for diagnosis and management of PPA. In order to pursue the objective, four studies were conducted. The first study approached the pathophysiology of nonfluent PPA, which remains poorly understood. Here, we compared quantitatively speech parameters in patients with nonfluent PPA versus healthy older individuals under altered auditory feedback, which has been shown to modulate normal speech output. Patients (n=15) and healthy volunteers (n=17) were recorded while reading aloud under delayed auditory feedback (DAF) with latency 0, 50 or 200 ms and under DAF at 200 ms plus 0.5 octave upward pitch shift. DAF in healthy older individuals was associated with reduced speech rate and emergence of speech sound errors, particularly at latency 200 ms. Up to a third of the healthy older group under DAF showed speech slowing and frequency of speech sound errors within the range of the nonfluent PPA cohort. Our findings suggest that (in addition to any anterior, primary language output disorder) these key features of nonfluent PPA may reflect distorted speech input signal processing, as simulated by DAF. DAF may constitute a novel candidate pathophysiological model of posterior dorsal cortical language pathway dysfunction in nfvPPA. The objective of the second study was to test whether data mining techniques, through an unsupervised learning approach, support the three-group diagnostic model of PPA versus the existence of two main/classic groups. A series of 155 PPA patients observed in a clinical setting and subjected to at least one neuropsychological/language assessment was studied. Several demographic, clinical and neuropsychological attributes, grouped in distinct sets, were introduced in unsupervised learning methods (Expectation Maximization, K-Means, X-Means, Hierarchical Clustering and Consensus Clustering). Unsupervised learning methods revealed two main groups consistently obtained throughout all the analyses (with different algorithms and different set of attributes). One group included most of the nonfluent and some logopenic PPA cases while the other was mainly composed of semantic and logopenic PPA cases. Clustering the patients in a larger number of groups (k > 2) revealed some clusters composed mostly by nonfluent or by semantic PPA cases. However, we could not evidence any group chiefly composed of logopenic PPA cases. Hence, findings obtained with the application of unsupervised data mining approaches do not clearly support a logopenic PPA. However further, supervised learning studies may indicate distinct results. Behaviour changes may occur early in PPA but the frequency of these symptoms across the three variants is still controversial. In the third study, 94 consecutive PPA patients (26 nonfluent, 36 semantic, 32 logopenic) underwent language and neuropsychological assessments. The presence of behavioural changes was ascertained by semi-structured informant-based interviews using the Blessed Dementia Rating Scale. Eighty-two percent of the cases endorsed at least one behaviour change. Nonfluent patients presented significantly more behaviour changes and scored more often (46.2%) the item “hobbies relinquished” when compared to logopenic patients. These differences in behaviour symptoms probably reflect distinct underlying neurodegenerative diseases. PPA is a neurodegenerative disorder with no effective pharmacological treatment. Cognition-based interventions are adequate alternatives, but their benefit has not been thoroughly explored. The aim of this last investigation was to study the effect of speech and language therapy (SLT) on naming ability in PPA. An open parallel prospective longitudinal study involving two centers was designed to compare patients with PPA submitted to SLT (1 h/week for 11 months, on average) with patients receiving no therapy. Twenty patients were enrolled and undertook baseline language and neuropsychological assessments; among them, 10 received SLT and 10 constituted an age- and education-matched historical control group. The primary outcome measure was the change in group mean performance on the Snodgrass and Vanderwart Naming Test between baseline and follow-up assessments. Intervention and control groups did not significantly differ on demographic and clinical variables at baseline. A mixed repeated measures ANOVA revealed a significant main effect of therapy (F(1,18) = 10.763; p = 0.005) on the performance on the Snodgrass and Vanderwart Naming Test. Although limited by a non-randomized open study design with a historical control group, the present study suggests that SLT may have a benefit in PPA, and it should prompt a randomized, controlled, rater-blind clinical trial. Conclusion: Despite the recent harmonization efforts, the delineation of certain PPA variants is still controversial. The present results show that neuropsychology is a key instrument not only for the clear definition of PPA subtypes but also for the study of the abnormal mechanisms and features underlying the main forms of PPA. Moreover, a neuropsychological approach to disease management seems to be feasible. Specifically, SLT emerges as an alternative and adequate approach to tackle the increasing language deficits experienced in all PPA phenotypes for some time. The emergence of promising disease-modifying therapies in the context of FTLD, in association with these cognitive-based interventions, will certainly be the future of PPA disease management.
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Fundação para a Ciência e a Tecnologia
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SFRH
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SFRH/BD/75710/2011