Article

Differentiating primary progressive aphasias in a brief sample of connected speech

From the Department of Neurology (S.A., E.E., J.O., J.P., A.B., D.W., J.H., C.M., D.J.I., K.R., M.G.) and Center for Neurodegenerative Disease Research (D.J.I.), Perelman School of Medicine of the University of Pennsylvania, Philadelphia.
Neurology (Impact Factor: 8.3). 06/2013; 81(4). DOI: 10.1212/WNL.0b013e31829c5d0e
Source: PubMed

ABSTRACT A brief speech expression protocol that can be administered and scored without special training would aid in the differential diagnosis of the 3 principal forms of primary progressive aphasia (PPA): nonfluent/agrammatic PPA, logopenic variant PPA, and semantic variant PPA.
We used a picture-description task to elicit a short speech sample, and we evaluated impairments in speech-sound production, speech rate, lexical retrieval, and grammaticality. We compared the results with those obtained by a longer, previously validated protocol and further validated performance with multimodal imaging to assess the neuroanatomical basis of the deficits.
We found different patterns of impaired grammar in each PPA variant, and additional language production features were impaired in each: nonfluent/agrammatic PPA was characterized by speech-sound errors; logopenic variant PPA by dysfluencies (false starts and hesitations); and semantic variant PPA by poor retrieval of nouns. Strong correlations were found between this brief speech sample and a lengthier narrative speech sample. A composite measure of grammaticality and other measures of speech production were correlated with distinct regions of gray matter atrophy and reduced white matter fractional anisotropy in each PPA variant.
These findings provide evidence that large-scale networks are required for fluent, grammatical expression; that these networks can be selectively disrupted in PPA syndromes; and that quantitative analysis of a brief speech sample can reveal the corresponding distinct speech characteristics.

3 Followers
 · 
105 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Logopenic progressive aphasia is the most recently described clinical variant of primary progressive aphasia (PPA), defined by impairment of lexical retrieval and sentence repetition. Unlike other PPA variants, the logopenic variant of PPA (lv-PPA) is commonly associated with Alzheimer's disease (AD), a fact that is relevant to the selection of patients for clinical trials and disease-modifying therapies. Despite the straightforward definition and coherent pathological association, the existence of lv-PPA has been challenged, as its distinction from AD or other PPA variants can be difficult. Despite these issues, lv-PPA patients display characteristic linguistic deficits, a pattern of brain atrophy, and possibly genetic susceptibility, which warrant considering this variant as a discrete AD endophenotype. More specific clinical and anatomical markers can strengthen the consistency of this syndrome.
    Current Neurology and Neuroscience Reports 11/2013; 13(11):396. DOI:10.1007/s11910-013-0396-6 · 3.67 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this review, the authors outline a clinical approach to frontotemporal lobar degeneration (FTLD), a term coined to describe a pathology associated with atrophy of the frontal and temporal lobes commonly seen with abnormal protein aggregates. It accounts for ∼10% of pathologically confirmed dementias. The three clinical syndromes associated with FTLD are jointly classified as frontotemporal dementia (FTD) and include behavioral variant frontotemporal dementia (bvFTD), nonfluent-agrammatic primary progressive aphasia (nfvPPA), and semantic variant PPA (svPPA; left: l-svPPA and right: r-svPPA). All syndromes have differential impairment in behavioral (bvFTD; r-svPPA), executive (bvFTD; nfvPPA), and language (nfvPPA; svPPA) functions early in the disease course. With all three there is relative sparing of short-term memory and visuospatial abilities early on, and with the two language syndromes, nfvPPA and svPPA, behavior is also intact. Symptoms are associated with specific atrophy patterns, lending unique imaging signatures to each syndrome (frontal: bvFTD and nfvPPA; temporal: svPPA). Common proteinopathies involve accumulation of tau, transactive response DNA binding protein 43, and fusion in sarcoma protein. Parkinsonism presents in all syndromes, especially cases with tau pathology and MAPT or GRN mutations. nfvPPA often has corticobasal degeneration or progressive supranuclear palsy as the underlying neuropathological substrate. bvFTD co-occurs with motor neuron disease in ∼15% of cases, and many such cases are due to C9Orf72 mutations. Other common genetic mutations in FTLD involve GRN and MAPT. Behavioral symptoms are best managed by selective serotonin reuptake inhibitors, while atypical antipsychotics should be used with caution given side effects. Promising etiologic treatments include anti-tau antibodies, antisense oligonucleotides, and progranulin enhancers.
    Seminars in Neurology 04/2014; 34(2):189-201. DOI:10.1055/s-0034-1381735 · 1.78 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We examined narrative discourse in amyotrophic lateral sclerosis (ALS) to assess the role of executive functioning in support of language and the neuroanatomical basis for such support.METHODS: We analyzed a semistructured speech sample in 26 patients with ALS and 19 healthy seniors for narrative discourse features of coherence. Regression analyses related a measure of discourse coherence ("local connectedness") to gray matter atrophy and reduced white matter fractional anisotropy.RESULTS: Patients with ALS were impaired relative to controls on measures of discourse adequacy, including local connectedness and maintenance of the theme. These discourse measures were related to measures of executive functioning but not to motor functioning. Regressions related local connectedness to gray matter atrophy in ventral and dorsal prefrontal regions and to reduced fractional anisotropy in white matter tracts mediating projections between prefrontal regions.CONCLUSION: Patients with ALS exhibit deficits in their ability to organize narrative discourse. These deficits appear to be related in part to executive limitations. Consistent with the hypothesis that ALS is a multisystem disorder, this deficit is related to disease in prefrontal regions.
    Neurology 07/2014; 83(6). DOI:10.1212/WNL.0000000000000670 · 8.30 Impact Factor