Primary Progressive Aphasia Subtypes Research Articles

Aβ amyloid and glucose metabolism in three variants of primary progressive aphasia

Alzheimer's disease (AD) is found at autopsy in up to one third of patients with primary progressive aphasia (PPA), but clinical features that predict AD pathology in PPA are not well defined. We studied the relationships between language presentation, Abeta amyloidosis, and glucose metabolism in three PPA variants using [11C]-Pittsburgh compound B ([11C]PIB) and [18F]-labeled fluorodeoxyglucose positron emission tomography ([18F]FDG-PET). Patients meeting PPA criteria (N = 15) were classified as logopenic aphasia (LPA), progressive nonfluent aphasia (PNFA), or semantic dementia (SD) based on language testing. [11C]PIB distribution volume ratios were calculated using Logan graphical analysis (cerebellar reference). [18F]FDG images were normalized to pons. Partial volume correction was applied. Elevated cortical PIB (by visual inspection) was more common in LPA (4/4 patients) than in PNFA (1/6) and SD (1/5) (p < 0.02). In PIB-positive PPA, PIB uptake was diffuse and indistinguishable from the pattern in matched AD patients (n = 10). FDG patterns were focal and varied by PPA subtype, with left temporoparietal hypometabolism in LPA, left frontal hypometabolism in PNFA, and left anterior temporal hypometabolism in SD. FDG uptake was significant asymmetric (favoring left hypometabolism) in PPA (p < 0.005) but not in AD. LPA is associated with Abeta amyloidosis, suggesting that subclassification of PPA based on language features can help predict the likelihood of AD pathology. Language phenotype in PPA is closely related to metabolic changes that are focal and anatomically distinct between subtypes, but not to amyloid deposition patterns that are diffuse and similar to AD.

Primary Progressive Aphasia

The diagnosis of primary progressive aphasia (PPA) is made in any patient in whom a language impairment (aphasia), caused by a neurodegenerative disease (progressive), constitutes the most salient aspect of the clinical picture (primary). The language impairment can be fluent or nonfluent and may or may not interfere with word comprehension. Memory for recent events is relatively preserved although memory scores obtained in verbally mediated tests may be abnormal. Lesser changes in behavior and object recognition may be present but are not the leading factors that bring the patient to medical attention. This selective clinical pattern is most conspicuous in the initial stages of the disease. Progressive nonfluent aphasia and some types of semantic dementia can be considered subtypes of PPA. Initially brought to the attention of contemporary literature 25 years ago, PPA has recently witnessed substantial progress related to its neurolinguistic features, neuroanatomy, imaging, neuropathology, genetics, and risk factors.

Visualizing language deterioration in progressive aphasias

In this issue of Neurology , Gorno-Tempini et al.1 and Rosen et al.2 present studies characterizing neuroimaging and behavioral changes in subtypes of primary progressive aphasia (PPA). They add new information to a large and growing body of literature on the frontotemporal lobar degenerations (FTLD), the second most common cause of dementia in persons under age 65. As this group of illnesses is still less common than other causes of dementia, such as Alzheimer disease (AD) and vascular dementia, both studies were made possible through the systematic study of a large number of such patients performed at a tertiary referral center. In order to explore the anatomic basis for mutism in progressive nonfluent aphasia (PNFA), one form of FTLD, Gorno-Tempini et al.1 compared gray matter volumes in regions of interest between mute and non-mute patients with PNFA using voxel-based morphometry. Many patients with PNFA eventually develop mutism so it is important to note that patients and controls in this study were matched for disease duration. These investigators found more severe atrophy in the left anterior insula and inferior frontal lobe in persons with PNFA with more prominent atrophy in the pars opercularis and underlying basal ganglia in …

Paradoxical features of word finding difficulty in primary progressive aphasia

Impaired word retrieval is a main symptom of primary progressive aphasia (PPA). The cognitive features of this impairment in PPA are poorly understood. We studied 12 patients with PPA (6 English-speaking and 6 Dutch-speaking), 7 patients with early-stage clinically probable Alzheimer's disease (PRAD), 5 patients with mild cognitive impairment (MCI), and 15 age-matched, cognitively intact, control subjects. Subjects had to name a picture (the probe), which was preceded by a written word (the prime) that could be the correct name of the picture, a noun belonging to the same semantic subcategory (related prime), a semantically unrelated noun (unrelated prime), or a pseudoword (neutral control). Naming latencies were longer in PPA and PRAD patients than in control subjects. Critically, the interaction between group and prime type was highly significant. PPA patients named the probe more slowly after a related compared with an unrelated prime. In contrast, PRAD patients, mild cognitive impairment patients, and healthy control subjects tended to name the probe faster when it was preceded by a related prime. The semantic interference effect in PPA generalized across languages and PPA subtypes. Selection among competing word forms sharing a same semantic field is abnormal in PPA. The semantic interference effect constitutes a positive distinguishing feature between PPA and PRAD.

Introducción

While patients with primary progressive aphasia (PPA) typically present with predominant language impairment, behavioural symptoms, such as apathy, are often under-recognised. We aimed to systematically characterise apathy across the three recognised subtypes of PPA, plus atypical right-lateralised presentations of semantic dementia, and to evaluate the impact of apathy on carer burden and psychological wellbeing.Baseline assessments from 114 PPA patients were included: 31 left semantic dementia (left SD) 16 right semantic dementia (right SD), 30 progressive nonfluent aphasia (PNFA) and 37 logopenic progressive aphasia (LPA). Clinician (Neuropsychiatric Inventory; NPI) and carer rated (Cambridge Behavioural Inventory; CBI, Frontal Systems Behaviour Scale; FrSBe) measures were used to quantify symptoms of apathy, and carer burden and psychological wellbeing were determined using the Zarit Burden Interview and Depression, Anxiety and Stress Scale.On the NPI, symptoms of apathy were present in 39% left SD, 56% right SD, 33% PNFA and 43% LPA patients. Multiple regression analysis revealed that 17.9% of the variance in carer burden was uniquely explained by scores on carer rated measures of apathy (CBI, FrSBe), even after accounting for diagnosis, disease duration, and cognitive and language impairment.Apathy is much more common than current diagnostic criteria for PPA would suggest, though the severity of apathy is similar across patient groups. Increased awareness and routine assessments of apathy symptoms are needed, together with targeted pharmacological and behavioural interventions. Moreover, as apathy substantially contributes to carer burden in PPA, psychoeducation addressing behavioural symptoms may be beneficial.

Primary progressive aphasia

Primary progressive aphasia (PPA) is a focal dementia characterized by an isolated and gradual dissolution of language function. The disease starts with word-finding disturbances (anomia) and frequently proceeds to impair the grammatical structure (syntax) and comprehension (semantics) of language. The speech output in PPA can be fluent or nonfluent. Memory, visual processing, and personality remain relatively well-preserved until the advanced stages and help to distiguish PPA from frontal lobe dementia and the typical forms of Alzheimer's disease. The term "semantic dementia" was originally introduced to designate a different group of patients with a combination of verbal and visual processing deficits. In practice, however, this diagnosis is also being used in a variant sense to denote a subtype of PPA with fluent speech and impaired comprehension, even in the absence of visual processing deficits. Insofar as the diagnosis of semantic dementia can have these two different meanings, it is important to specify whether it is being used in the original sense or to denote a subtype of PPA. Structural and physiological neuroimaging confirms the selective predilection of PPA for the left hemisphere, especially for its language-related cortices. A few patients with PPA display the neuropathological markers of Alzheimer's disease, but in an unusual distribution. The majority of the autopsies in PPA have shown either Pick's disease or lobar atrophy without distinctive histopathology. The suggestion has been made that PPA and frontal lobe dementia constitute phenotypical variations of a unitary disease process within the "Pick-lobar atrophy" spectrum. Recent advances in chromosome 17-linked dementias justify a rigorous search for tau polymorphisms and tauopathy in sporadic PPA. An informed approach to this syndrome will increase the effectiveness with which clinicians can address the unique challenges associated with the diagnosis and care of PPA.