Primary Progressive Apraxia Research Articles

APOE ε4 influences β-amyloid deposition in primary progressive aphasia and speech apraxia

BackgroundApolipoprotein E ε4 (APOE ε4) is a risk factor for β-amyloid deposition in Alzheimer's disease dementia. Its influence on β-amyloid deposition in speech and language disorders, including primary progressive aphasia (PPA), is unclear. MethodsOne hundred thirty subjects with PPA or progressive speech apraxia underwent APOE genotyping and Pittsburgh compound B (PiB) PET scanning. The relationship between APOE ε4 and PiB status, as well as severity and regional distribution of PiB, was assessed. ResultsForty-five subjects had an APOE ε4 allele and 60 subjects were PiB-positive. The odds ratio for a subject with APOE ε4 being PiB-positive compared with a subject without APOE ε4 being PiB-positive was 10.2 (95% confidence interval, 4.4–25.5; P < .0001). The APOE ε4 allele did not influence regional PiB distribution or severity. ConclusionAPOE ε4 increases the risk of β-amyloid deposition in PPA and progressive speech apraxia but does not influence regional β-amyloid distribution or severity.

Nonverbal oral apraxia in primary progressive aphasia and apraxia of speech.

The goal of this study was to explore the prevalence of nonverbal oral apraxia (NVOA), its association with other forms of apraxia, and associated imaging findings in patients with primary progressive aphasia (PPA) and progressive apraxia of speech (PAOS). Patients with a degenerative speech or language disorder were prospectively recruited and diagnosed with a subtype of PPA or with PAOS. All patients had comprehensive speech and language examinations. Voxel-based morphometry was performed to determine whether atrophy of a specific region correlated with the presence of NVOA. Eighty-nine patients were identified, of which 34 had PAOS, 9 had agrammatic PPA, 41 had logopenic aphasia, and 5 had semantic dementia. NVOA was very common among patients with PAOS but was found in patients with PPA as well. Several patients exhibited only one of NVOA or apraxia of speech. Among patients with apraxia of speech, the severity of the apraxia of speech was predictive of NVOA, whereas ideomotor apraxia severity was predictive of the presence of NVOA in those without apraxia of speech. Bilateral atrophy of the prefrontal cortex anterior to the premotor area and supplementary motor area was associated with NVOA. Apraxia of speech, NVOA, and ideomotor apraxia are at least partially separable disorders. The association of NVOA and apraxia of speech likely results from the proximity of the area reported here and the premotor area, which has been implicated in apraxia of speech. The association of ideomotor apraxia and NVOA among patients without apraxia of speech could represent disruption of modules shared by nonverbal oral movements and limb movements.

Nonverbal Oral Apraxia in Primary Progressive Aphasia and Apraxia of Speech (P2.166)

Nonverbal Oral Apraxia in Primary Progressive Aphasia and Apraxia of Speech (P2.166)

Pathophysiology of language, speech and emotions in neurodegenerative disease

Studying neurodegenerative diseases has greatly expanded our knowledge of language, speech and emotion as these diseases can affect areas not typically seen with stroke or tumor. Newer imaging techniques such as voxel based morphometry), fluorodeoxyglucose (F18) positron emission tomography and functional magnetic resonance imaging have allowed localization of these deficits and a greater understanding of the language network targeted by these progressive neurodegenerative illnesses. This review illustrates these important points by describing five syndromes, using clinical cases and then noting the anatomy, typical pathology, and proposed pathophysiology. The syndromes are Progressive Nonfluent Aphasia, Semantic Dementia, Logopenic Aphasia, Primary Progressive Apraxia of Speech and Dysprosody of Speech. Clinicians recognizing these syndromes using the associated clinico-anatomic patterns will lead to more accurate diagnosis and improved patient counseling and management. Further, patients may be included in appropriate clinical trials when their doctors are aware of the most likely pathology.

Primary Progressive Aphasia and Apraxia of Speech

Primary progressive aphasia is a neurodegenerative syndrome characterized by progressive language dysfunction. The majority of primary progressive aphasia cases can be classified into three subtypes: nonfluent/agrammatic, semantic, and logopenic variants. Each variant presents with unique clinical features, and is associated with distinctive underlying pathology and neuroimaging findings. Unlike primary progressive aphasia, apraxia of speech is a disorder that involves inaccurate production of sounds secondary to impaired planning or programming of speech movements. Primary progressive apraxia of speech is a neurodegenerative form of apraxia of speech, and it should be distinguished from primary progressive aphasia given its discrete clinicopathological presentation. Recently, there have been substantial advances in our understanding of these speech and language disorders. The clinical, neuroimaging, and histopathological features of primary progressive aphasia and apraxia of speech are reviewed in this article. The distinctions among these disorders for accurate diagnosis are increasingly important from a prognostic and therapeutic standpoint.

An Elderly Woman With Difficulty Reading and Abnormal Eye Movements

An Elderly Woman With Difficulty Reading and Abnormal Eye Movements

The effects of initiation, termination and inhibition impairments on speech rate in a case of progressive nonfluent aphasia with progressive apraxia of speech with frontotemporal degeneration

Recent research into nonfluent forms of primary progressive aphasia and progressive apraxia of speech has highlighted the importance of speech rate as a diagnostic feature. We describe detailed investigation and comparison of speech rate (latencies and utterance length in single word/nonword production and speech rate in connected speech) on a range of experimental tasks in a man with progressive speech deterioration of 10 years duration from Pick's Disease. C.S. had a progressive nonfluent aphasia (PNFA) together with progressive apraxia of speech (pAOS) with an absence of significant interlectual, phonological or semantic impairment. C.S. showed increased latencies but reduced word length compared to matched controls on single word and nonword repetition and reading, an absence of a syllabic length effect in either single word/nonword tasks or connected speech tasks. Further investigation suggested that underlying his speech production impairments were problems with speech initiation, termination and inhibition. Most impairments worsened with progression over a 12-month period. Results provide support for the view that progressive apraxia of speech presents differently to apraxia of speech following stroke and, especially at advanced stages, involves deterioration in more central and supportive cognitive processes.

Primary progressive apraxia: a syndrome difficult to categorize

Center of Computed Tomography (CETAC), INC, Curitiba PR, Brazil.Correspondece: Ricardo Krause Martinez de Souza; Instituto de Neurologia de Curitiba; Rua Jeremias Maciel Perretto 300; 81210-310 Curitiba PR - Brasil. E-mail: ricardo.neurologia@hotmail.comConflict of Interest: There is no conflict of interest to declare.Received 25 May 2012; Received in final form 13 September 2012; Accepted 20 September 2012.

Neuroimaging comparison of primary progressive apraxia of speech and progressive supranuclear palsy

Primary progressive apraxia of speech, a motor speech disorder of planning and programming, is a tauopathy that has overlapping histological features with progressive supranuclear palsy. We aimed to compare, for the first time, atrophy patterns, as well as white matter tract degeneration, between these two syndromes. Sixteen primary progressive apraxia of speech subjects were age- and gender-matched to 16 progressive supranuclear palsy subjects and 20 controls. All subjects were prospectively recruited, underwent neurological and speech evaluations and 3.0-Tesla magnetic resonance imaging. Grey and white matter atrophy was assessed using voxel-based morphometry and atlas-based parcellation, and white matter tract degeneration was assessed using diffusion tensor imaging. All progressive supranuclear palsy subjects had typical oculomotor/gait impairments, but none had speech apraxia. Both syndromes showed grey matter loss in supplementary motor area, white matter loss in posterior frontal lobes and degeneration of the body of the corpus callosum. Whilst lateral grey matter loss was focal, involving superior premotor cortex, in primary progressive apraxia of speech, loss was less focal extending into prefrontal cortex in progressive supranuclear palsy. Caudate volume loss and tract degeneration of superior cerebellar peduncles were also observed in progressive supranuclear palsy. Interestingly, area of the midbrain was reduced in both syndromes compared to controls, although this was greater in progressive supranuclear palsy. Although neuroanatomical differences were identified between these distinctive clinical syndromes, substantial overlap was also observed, including midbrain atrophy, suggesting these two syndromes may have common pathophysiological underpinnings.

Primary Progressive Apraxia of Speech (PAS): A Distinct Neurodegenerative Syndrome (P07.167)

Primary Progressive Apraxia of Speech (PAS): A Distinct Neurodegenerative Syndrome (P07.167)

Primary progressive apraxia of speech (AOS) in a patient with Pick's disease with Pick bodies: a neuropsychological and anatomical study and review of literatures

A 56-year-old right-handed man suffered from progressive apraxia of speech (AOS), characterized by agrammatism and buccofacial apraxia. He also became mute at the later stages of the disease progression. At autopsy, the left precentral gyrus, pars opercularis, and hippocampus showed severe atrophy. Pick bodies and Pick cells were observed. In this report, we also review previous case reports of AOS. Pick's disease is among the most commonly associated of the major diseases. Brain lesions associated with AOS may be found in regions such as the precentral gyrus and the pars opercularis in the left hemisphere.

Characterizing a neurodegenerative syndrome: primary progressive apraxia of speech

Apraxia of speech is a disorder of speech motor planning and/or programming that is distinguishable from aphasia and dysarthria. It most commonly results from vascular insults but can occur in degenerative diseases where it has typically been subsumed under aphasia, or it occurs in the context of more widespread neurodegeneration. The aim of this study was to determine whether apraxia of speech can present as an isolated sign of neurodegenerative disease. Between July 2010 and July 2011, 37 subjects with a neurodegenerative speech and language disorder were prospectively recruited and underwent detailed speech and language, neurological, neuropsychological and neuroimaging testing. The neuroimaging battery included 3.0 tesla volumetric head magnetic resonance imaging, [18F]-fluorodeoxyglucose and [11C] Pittsburg compound B positron emission tomography scanning. Twelve subjects were identified as having apraxia of speech without any signs of aphasia based on a comprehensive battery of language tests; hence, none met criteria for primary progressive aphasia. These subjects with primary progressive apraxia of speech included eight females and four males, with a mean age of onset of 73 years (range: 49–82). There were no specific additional shared patterns of neurological or neuropsychological impairment in the subjects with primary progressive apraxia of speech, but there was individual variability. Some subjects, for example, had mild features of behavioural change, executive dysfunction, limb apraxia or Parkinsonism. Voxel-based morphometry of grey matter revealed focal atrophy of superior lateral premotor cortex and supplementary motor area. Voxel-based morphometry of white matter showed volume loss in these same regions but with extension of loss involving the inferior premotor cortex and body of the corpus callosum. These same areas of white matter loss were observed with diffusion tensor imaging analysis, which also demonstrated reduced fractional anisotropy and increased mean diffusivity of the superior longitudinal fasciculus, particularly the premotor components. Statistical parametric mapping of the [18F]-fluorodeoxyglucose positron emission tomography scans revealed focal hypometabolism of superior lateral premotor cortex and supplementary motor area, although there was some variability across subjects noted with CortexID analysis. [11C]-Pittsburg compound B positron emission tomography binding was increased in only one of the 12 subjects, although it was unclear whether the increase was actually related to the primary progressive apraxia of speech. A syndrome characterized by progressive pure apraxia of speech clearly exists, with a neuroanatomic correlate of superior lateral premotor and supplementary motor atrophy, making this syndrome distinct from primary progressive aphasia.

Effects of alternative communication on the communicative effectiveness of an individual with a progressive language disorder

This study was designed to investigate the effects of two different modes of communication on the communicative output of an individual who is no longer able to communicate verbally, presenting with a primary progressive aphasia and apraxia of speech. The two treatment approaches included training the patient with a text-to-speech alternative communication device and with American sign language. An alternating treatment design was used to compare two communicative approaches (an alternative communication device and American sign language) on the subject's communicative effectiveness. Communicative effectiveness was measured in terms of number of words, correct information units and percentage correct information units, using a protocol that was adapted to quantify the output generated by the alternative communication device and American sign language. Increases across all three measures resulted for both the alternative communication device and American sign language. The clinical implications are explored, and the results add to existing studies regarding treatment possibilities using alternative communication for individuals who present with a progressive speech and language disorder, without concomitant cognitive deficits.

The Role of the Dynamic Body Schema in Praxis: Evidence from Primary Progressive Apraxia

On an influential model of limb praxis, ideomotor apraxia results from damage to stored gesture representations or disconnection of representations from sensory input or motor output (Heilman & Gonzalez Rothi, 1993; Gonzalez Rothi et al., 1991). We report data from a patient with progressive ideomotor limb apraxia which cannot be readily accommodated by this model. The patient, BG, is profoundly impaired in gesturing to command, to sight of object, and to imitation, but gestures nearly normally with tool in hand and recognizes gestures relatively well. In addition, performance is profoundly impaired on imitation of meaningless gestures and on tasks requiring spatiomotor transformations of body-position information. We provide evidence that BG's apraxia is largely attributable to impairments external to the stored gesture system in procedures coding the dynamic positions of the body parts of self and others; that is, the body schema. We propose a model of a dynamic, interactive praxis system subserved by posterior parietal cortex in which stored representational elements, when present, provide “top-down” support to spatiomotor procedures computed on-line. In addition to accounting for BG's performance, this model accommodates a common pattern of ideomotor apraxia more readily than competing accounts.

Primary progressive apraxia

We have investigated the clinical symptoms and pathological findings of primary progressive apraxia (PPA) in 31 cases in the literature and four of our own cases. The mean age of onset of the initial symptoms was 60.5 years, with a slight predilection for males. The time between the onset of symptoms and the medical examination was 3.1 years. The mean duration of illness was 4.2 years for the surviving cases and 6.8 years for the four deceased cases. The most frequently encountered apraxia symptom is a limb‐kinetic apraxia. It has become known that other forms of apraxia such as apraxia of speech, buccofacial apraxia and dressing apraxia, which are not established as a symptomatic condition, can manifest themselves in an isolated manner. Neurological examination often reveals extrapyramidal symptoms such as rigidity and myoclonus from the beginning of the illness. As for the higher functional problems, apraxia is often accompanied by a distrubance of calculation. With regard to the radiological findings, computed tomography and magnetic resonance imaging show characteristic atrophy with left–right inequality and diffuse disturbance in single photon emission computed tomography‐positron emission tomography study is seen on the more severely atrophic side. In autopsy and biopsy examinations, one patient was diagnosed with corticobasal degeneration, three cases were diagnosed with Alzheimer's disease and one with Pick's disease. PPA is a heterogeneous symptomatic condition. This paper confirm the existence of apraxias which were not previously recognized as concrete symptomatic conditions; furthermore, it is suggested that the cerebral system of behavioral association might be more subdivided than was formerly considered.