Quantitating Severity and Progression in Primary Progressive Aphasia

Frontotemporal Dementia Unit, Department of Neurology, Massachusetts Alzheimer's Disease Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Journal of Molecular Neuroscience (Impact Factor: 2.34). 05/2011; 45(3):618-28. DOI: 10.1007/s12031-011-9534-2
Source: PubMed


Primary progressive aphasia (PPA) is an insidiously progressive clinical syndrome that includes at its core an impairment in language. From a clinical perspective, there are a variety of diagnostic challenges; international consensus has only recently been reached on the nomenclature for specific clinical subtypes. There are at present no established treatments, and efforts to develop treatments have been hampered by the lack of standardized methods to monitor progression of the illness. This is further complicated by the multiplicity of underlying neuropathologies. Although measures developed from work with stroke aphasia and from work with disorders such as Alzheimer's disease and frontotemporal dementia have provided a valuable foundation for monitoring progression, PPA presents unique challenges to clinicians aiming to quantify impairments for the purposes of full characterization and monitoring, and ultimately with the goal of designing clinical trials of interventions to make a meaningful difference in patients' lives. In this review, I will summarize the main points made in my presentation at the 2010 International Conference on Frontotemporal Dementia, expand from there to summarize our current approach to monitoring progression of PPA, and finally will outline some ideas about goals for the development of better tools for this purpose.

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Available from: Bradford Dickerson, Jan 21, 2014
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    ABSTRACT: Introduction: Primary progressive aphasia (PPA) is a clinical syndrome characterised by a progressive decline in language and speech of neurodegenerative origin. Major breakthroughs made in recent years have lent us a better understanding of this syndrome, which may be the first manifestation of any of a number of neurodegenerative diseases. Development: We reviewed the main aspects of PPA epidemiology, clinical manifestations, diagnosis, aetiology and treatment. Most cases manifest sporadically and the typical age of onset is between 50 and 70 years. Three clinically distinct variants have been described: nonfluent or agrammatic PPA, semantic PPA and logopenic PPA. Each of these variants tends to be associated with specific histopathological findings, but clinical diagnostic methods are imperfect predictors of underlying pathology. Anatomical and functional neuroimaging can provide useful biomarkers. Several treatments have been proposed, and while no clear benefits have been demonstrated, acetylcholinesterase inhibitors may be useful, especially in the logopenic variant. Conclusions: PPA is an emerging syndrome which may be more prevalent than we might expect. It was previously listed as part of the frontotemporal dementia spectrum, and it is also related to Alzheimer disease. Clinical diagnosis, complemented by a biomarker evaluation, may predict the underlying pathology, which in turn will improve treatment possibilities.
    Neurologia (Barcelona, Spain) 06/2012; DOI:10.1016/j.nrl.2012.04.003 · 1.38 Impact Factor
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    ABSTRACT: Review of clinical and biological features of primary progressive aphasia (PPA). The PPA syndrome arises when language-dominant (usually left) hemisphere becomes the principal target of neurodegeneration. Depending on the distribution of neuronal loss within the language network, agrammatic (PPA-G), logopenic (PPA-L), and semantic (PPA-S) subtypes are identified. The most common underlying neuropathology is frontotemporal degeneration with tauopathy in PPA-G, frontotemporal degeneration with TDP-43 proteinopathy in PPA-S, and Alzheimer pathology in PPA-L. When Alzheimer pathology is detected, the neurofibrillary tangles show lower entorhinal-to-neocortical ratios and greater leftward asymmetry in PPA than in the typical amnestic dementia of Alzheimer disease. The ε4 allele of APOE, a major risk factor for Alzheimer pathology in amnestic dementias, is not a risk factor for Alzheimer pathology in PPA. These observations indicate that Alzheimer disease has biological variants with distinct patterns of lesion distribution and perhaps also molecular background. The selective vulnerability of the language network in PPA is likely to reflect complex interactions between factors that determine the type of histopathology, on one hand, and those that influence the resilience of the language network, on the other. A history of learning disability, including dyslexia, is emerging as one of the potential factors in this second group of determinants. Patient care in PPA should be individualized so that speech therapy can address the specific type of language impairment while pharmacologic therapy is directed to the underlying disease process.
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