Clinical course of primary progressive aphasia: clinical and FDG-PET patterns

Matías‐Guiu, Jordi A.; Cabrera‐Martín, María Nieves; Moreno‐Ramos, Teresa; García-Ramos, R.; Porta‐Etessam, Jesús; Carreras, José

doi:10.1007/s00415-014-7608-0

Cited by 40 publications

(31 citation statements)

References 36 publications

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“…In general, brain metabolic patterns were consistent with the current literature focused on group analysis studies (see as example [20]) providing more solid evidence at the single-subject level. As previously demonstrated (e.g., [14, 20, 38]), FDG-PET imaging supported an accurate in vivo diagnostic classification at the individual level within the PPA syndromes.…”

Section: Discussionsupporting

confidence: 87%

“…For example, in sv-PPA, the hypometabolism extended to the limbic structures [9, 16, 17], the fusiform gyrus [9–11, 18, 19], and the caudate and thalamus [9, 16]; in lv-PPA the prefrontal cortex is often involved [20, 21]. Very few studies explored functional metabolic changes in PPAs at an individual level [12, 13, 22], and notably, no study evaluated the role of FDG-PET patterns in PPAs for the prediction of progression to different dementia conditions at follow-up.…”

Section: Introductionmentioning

confidence: 99%

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The Role of Single-Subject Brain Metabolic Patterns in the Early Differential Diagnosis of Primary Progressive Aphasias and in Prediction of Progression to Dementia

Cerami

Dodich

Greco

et al. 2016

JAD

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Background and Objective: Primary progressive aphasia (PPA) is a clinical syndrome due to different neurodegenerative conditions in which an accurate early diagnosis needs to be supported by a reliable diagnostic tool at the individual level. In this study, we investigated in PPA the FDG-PET brain metabolic patterns at the single-subject level, in order to assess the case-to-case variability and its relationship with clinical-neuropsychological findings.Material and Methods: 55 patients (i.e., 11 semantic variant/sv-PPA, 19 non fluent variant/nfv-PPA, 17 logopenic variant/lv-PPA, 3 slowly progressive anarthria/SPA, and 5 mixed PPA/m-PPA) were included. Clinical-neuropsychological information and FDG-PET data were acquired at baseline. A follow-up of 27.4±12.55 months evaluated the clinical progression. Brain metabolism was analyzed using an optimized and validated voxel-based SPM method at the single-subject level.Results: FDG-PET voxel-wise metabolic assessment revealed specific metabolic signatures characterizing each PPA variant at the individual level, reflecting the underlying neurodegeneration in language networks. Notably, additional dysfunctional patterns predicted clinical progression to specific dementia conditions. In the case of nfv-PPA, a metabolic pattern characterized by involvement of parietal, subcortical and brainstem structures predicted progression to a corticobasal degeneration syndrome or to progressive supranuclear palsy. lv-PPA and sv-PPA cases who progressed to Alzheimer’s disease and frontotemporal dementia at the follow-up presented with extended bilateral patterns at baseline.Discussion: Our results indicate that FDG-PET voxel-wise imaging is a valid biomarker for the early differential diagnosis of PPAs and for the prediction of progression to specific dementia condition. This study supports the use of FDG-PET imaging quantitative assessment in clinical settings for a better characterization of PPA individuals and prognostic definition of possible endo-phenotypes.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

The Role of Single-Subject Brain Metabolic Patterns in the Early Differential Diagnosis of Primary Progressive Aphasias and in Prediction of Progression to Dementia

Cerami

Dodich

Greco

et al. 2016

JAD

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“…All participants underwent a detailed neurological and neuropsychological assessment, together with FDG-PET. Language assessment was performed following current recommendations for PPA (Gorno-Tempini et al, 2011 ), and has been described elsewhere (Matias-Guiu et al, 2015a ; Matías-Guiu et al, 2017b ). Amyloid imaging was available in 43 patients.…”

Section: Methodsmentioning

confidence: 99%

“…In addition, PPA patients may develop a second syndrome during the clinical course, such as atypical parkinsonian syndromes, behavioral symptoms like in behavioral variant frontotemporal dementia, dementia of Alzheimer's type, etc. (Rogalski and Mesulam, 2009 ; Matias-Guiu et al, 2015a ). However, despite the efforts to improve cognitive and linguistic assessment of patients and their classification, the diagnosis of PPA is still challenging, and the existence of two, three or more clinical variants is controversial (Vandenberghe, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Clustering Analysis of FDG-PET Imaging in Primary Progressive Aphasia

Matías‐Guiu

Álvarez

Ayala

et al. 2018

Front. Aging Neurosci.

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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.

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“…Several studies provide an initial insight into the progression of PPA [ 6 – 9 ]. Knopman et al [ 8 ] measured whole brain and ventricular volume changes within 1 year in FTLD patients, including 17 nfvPPA, 16 svPPA, and 9 lvPPA, amongst others.…”

Section: Introductionmentioning

confidence: 99%

A language-based sum score for the course and therapeutic intervention in primary progressive aphasia

et al. 2018

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BackgroundWith upcoming therapeutic interventions for patients with primary progressive aphasia (PPA), instruments for the follow-up of patients are needed to describe disease progression and to evaluate potential therapeutic effects. So far, volumetric brain changes have been proposed as clinical endpoints in the literature, but cognitive scores are still lacking. This study followed disease progression predominantly in language-based performance within 1 year and defined a PPA sum score which can be used in therapeutic interventions.MethodsWe assessed 28 patients with nonfluent variant PPA, 17 with semantic variant PPA, 13 with logopenic variant PPA, and 28 healthy controls in detail for 1 year. The most informative neuropsychological assessments were combined to a sum score, and associations between brain atrophy were investigated followed by a sample size calculation for clinical trials.ResultsSignificant absolute changes up to 20% in cognitive tests were found after 1 year. Semantic and phonemic word fluency, Boston Naming Test, Digit Span, Token Test, AAT Written language, and Cookie Test were identified as the best markers for disease progression. These tasks provide the basis of a new PPA sum score. Assuming a therapeutic effect of 50% reduction in cognitive decline for sample size calculations, a number of 56 cases is needed to find a significant treatment effect. Correlations between cognitive decline and atrophy showed a correlation up to r = 0.7 between the sum score and frontal structures, namely the superior and inferior frontal gyrus, as well as with left-sided subcortical structures.ConclusionOur findings support the high performance of the proposed sum score in the follow-up of PPA and recommend it as an outcome measure in intervention studies.Electronic supplementary materialThe online version of this article (10.1186/s13195-018-0345-3) contains supplementary material, which is available to authorized users.

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Clinical course of primary progressive aphasia: clinical and FDG-PET patterns

Cited by 40 publications

References 36 publications

The Role of Single-Subject Brain Metabolic Patterns in the Early Differential Diagnosis of Primary Progressive Aphasias and in Prediction of Progression to Dementia

The Role of Single-Subject Brain Metabolic Patterns in the Early Differential Diagnosis of Primary Progressive Aphasias and in Prediction of Progression to Dementia

Clustering Analysis of FDG-PET Imaging in Primary Progressive Aphasia

A language-based sum score for the course and therapeutic intervention in primary progressive aphasia

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