PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-18 (18)
 

Clipboard (0)
None

Select a Filter Below

Year of Publication
Document Types
1.  Distinct regional anatomic and functional correlates of neurodegenerative apraxia of speech and aphasia: an MRI and FDG-PET study 
Brain and language  2013;125(3):245-252.
Progressive apraxia of speech (AOS) can result from neurodegenerative disease and can occur in isolation or in the presence of agrammatic aphasia. We aimed to determine the neuroanatomical and metabolic correlates of progressive AOS and aphasia. Thirty-six prospectively recruited subjects with progressive AOS or agrammatic aphasia, or both, underwent the Western Aphasia Battery (WAB) and Token Test to assess aphasia, an AOS rating scale (ASRS), 3T MRI and 18-F fluorodeoxyglucose (FDG) PET. Correlations between clinical measures and imaging were assessed. The only region that correlated to ASRS was left superior premotor volume. In contrast, WAB and Token Test correlated with hypometabolism and volume of a network of left hemisphere regions, including pars triangularis, pars opercularis, pars orbitalis, middle frontal gyrus, superior temporal gyrus, precentral gyrus and inferior parietal lobe. Progressive agrammatic aphasia and AOS have non-overlapping regional correlations, suggesting that these are dissociable clinical features that have different neuroanatomical underpinnings.
doi:10.1016/j.bandl.2013.02.005
PMCID: PMC3660445  PMID: 23542727
apraxia of speech; aphasia; atrophy; Broca’s area; premotor cortex; hypometabolism
2.  Ideomotor Apraxia in Agrammatic and Logopenic Variants of Primary Progressive Aphasia 
Journal of neurology  2013;260(6):1594-1600.
There are few studies examining praxis in subjects with primary progressive aphasia. The aim of this study was to examine the pattern and severity of ideomotor apraxia in subjects with logopenic and agrammatic variants of primary progressive aphasia and to determine if the presence of ideomotor apraxia correlated with specific neuroanatomical structural abnormalities. Subjects with primary progressive aphasia were prospectively recruited and classified according to published criteria. Using the apraxia subtest of the Western Aphasia Battery, pattern and severity of ideomotor apraxia was examined in all subjects diagnosed with agrammatic and logopenic variants of primary progressive aphasia. The study included 47 subjects, 21 diagnosed with agrammatic variant of primary progressive aphasia and 26 with logopenic variant primary progressive aphasia. Subjects with agrammatic aphasia were older at onset than the logopenic variant (67.2 versus 61.7 years, p=0.02), but there was no difference in illness duration prior to evaluation. Those with logopenic aphasia showed more cognitive impairment on the Mini-Mental Status Examination (agrammatic=26.7/30, logopenic=22/30, p=0.002), and a trend for more severe language impairment as measured by Western Aphasia Battery-Aphasia Quotient (agrammatic=82.3, logopenic=75.2, p=0.11). Strong correlations were found between Western Aphasia Battery-Aphasia Quotient and total apraxia, instrumental apraxia, and complex apraxia, while average correlation were seen with upper limb apraxia and modest correlation with facial apraxia. After adjusting for age, mental status performance, and Western Aphasia Battery-Aphasia Quotient score, those with agrammatic aphasia had a higher degree of total apraxia (p=0.004), facial apraxia (p=0.03), instrumental apraxia (p=0.0006), and complex apraxia (p=0.0006) than those with logopenic aphasia. The agrammatic variant of primary progressive aphasia was associated with greater praxis deficits but less cognitive impairment than the logopenic variant. The presence of ideomotor apraxia was associated with grey matter loss in the left lateral premotor cortex with extension into the motor cortex. These findings suggest that although some affected areas in the agrammatic and logopenic variants of primary progressive aphasia overlap, there exists an area that is more affected in the agrammatic variant than the logopenic variant that accounts for the greater association of agrammatic aphasia with apraxia.
doi:10.1007/s00415-013-6839-9
PMCID: PMC3676701  PMID: 23358624
Primary progressive aphasia; Agrammatic; Logopenic; Apraxia; Ideomotor; Cortical atrophy
3.  Neuroimaging comparison of Primary Progressive Apraxia of Speech & Progressive Supranuclear Palsy 
Background
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.
Methods
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.
Results
All progressive supranuclear palsy subjects had typical occulomotor/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. While 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 was 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.
Discussion
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.
doi:10.1111/ene.12004
PMCID: PMC3556348  PMID: 23078273
Progressive supranuclear palsy; apraxia of speech; voxel-based morphometry; diffusion tensor imaging; midbrain
4.  Occupational differences between Alzheimer’s and aphasic dementias: implication for teachers 
We aimed to determine if there is an association between teaching and the development of progressive speech and language disorders (SLDs). Occupation was compared between 100 patients with a progressive SLD, 404 Alzheimer’s dementia patients, and the 2008 US census. In SLDs the most common occupation was teacher (22%), versus 8% in Alzheimer’s dementia. The odds ratio of being a teacher in SLDs compared to Alzheimer’s dementia was 3.4 (95% CI=1.87, 6.17). No differences were observed in the frequency of other occupations. The frequency of teachers was higher in SLDs compared to the US census; odds ratio of 6.9 (95% CI=4.3, 11.1). Farming, forestry and fishing occupations were more frequent in SLDs compared to the US census. We identified an association between progressive SLDs and the occupation of teaching. Since teaching is a communication demanding occupation, teachers may be more sensitive to the development of speech and language impairments.
doi:10.1177/1533317513494455
PMCID: PMC3920458  PMID: 23838322
Alzheimer’s; dementia; aphasia; teacher; occupation
5.  Elevated occipital β-amyloid deposition is associated with widespread cognitive impairment in logopenic progressive aphasia 
Background
Most subjects with logopenic primary progressive aphasia (lvPPA) have beta-amyloid (Aβ) deposition on Pittsburgh Compound B PET (PiB-PET), usually affecting prefrontal and temporoparietal cortices, with less occipital involvement.
Objectives
To assess clinical and imaging features in lvPPA subjects with unusual topographic patterns of Aβ deposition with highest uptake in occipital lobe.
Methods
Thirty-three lvPPA subjects with Aβ deposition on PiB-PET were included in this case-control study. Line-plots of regional PiB uptake were created, including frontal, temporal, parietal and occipital regions, for each subject. Subjects in which the line sloped downwards in occipital lobe (lvPPA-low), representing low uptake, were separated from those where the line sloped upwards in occipital lobe (lvPPA-high), representing unusually high occipital uptake compared to other regions. Clinical variables, atrophy on MRI, hypometabolism on F18-fluorodeoxyglucose PET, and presence and distribution of microbleeds and white matter hyperintensities (WMH) were assessed.
Results
Seventeen subjects (52%) were classified as lvPPA-high. Mean occipital PiB uptake in lvPPA-high was higher than all other regions, and higher than all regions in lvPPA-low. The lvPPA-high subjects performed more poorly on cognitive testing, including executive and visuospatial testing, but the two groups did not differ in aphasia severity. Proportion of microbleeds and WMH was higher in lvPPA-high than lvPPA-low. Parietal hypometabolism was greater in lvPPA-high than lvPPA-low.
Conclusions
Unusually high occipital Aβ deposition is associated with widespread cognitive impairment and different imaging findings in lvPPA. These findings help explain clinical heterogeneity in lvPPA, and suggest that Aβ influences severity of overall cognitive impairment but not aphasia.
doi:10.1136/jnnp-2013-305628
PMCID: PMC3920541  PMID: 23946416
6.  The Diagnosis and Understanding of Apraxia of Speech: Why Including Neurodegenerative Etiologies May Be Important 
Purpose
To discuss apraxia of speech (AOS) as it occurs in neurodegenerative disease (progressive AOS, or PAOS) and how its careful study may contribute to general concepts of AOS and help refine its diagnostic criteria.
Method
The paper summarizes our current understanding of the clinical features and neuroanatomical and pathologic correlates of PAOS and its relationship to primary progressive aphasia (PPA). It addresses similarities and differences between PAOS and stroke-induced AOS that may be relevant to improving our understanding of AOS in general.
Conclusions
PAOS is clinical disorder that should be distinguished from PPA. Its recognition is important to clinical care provided by speech-language pathologists, but it also has implications for neurologic localization and diagnosis, and prediction of underlying pathology and histochemistry. The clinical features of PAOS and stroke-induced AOS have not been explicitly compared, but they may not be identical because PAOS does not follow a vascular distribution, the brunt of cortical pathology is in the premotor and supplementary motor area, and its onset, rather than acute, is slowly progressive with potential for adaptation to gradual impairment. Careful description and study of PAOS may be a valuable source of information for refining our understanding of AOS in general.
doi:10.1044/1092-4388(2012/11-0309)
PMCID: PMC3907169  PMID: 23033445
apraxia of speech; progressive apraxia of speech; primary progressive aphasia; motor speech programming
7.  Parkinsonian motor features distinguish the agrammatic from logopenic variant of primary progressive aphasia 
Parkinsonism & related disorders  2012;18(7):890-892.
Background
Few studies have assessed parkinsonian motor features features across variants of primary progressive aphasia (PPA). Our objective was to compare degree of parkinsonian motor features features between two PPA variants.
Methods
Parkinsonian motor features were assessed with the Unified Parkinson’s Disease Rating scale in prospectively recruited PPA subjects, classified based on recently published criteria. Comparisons across groups were performed with Fisher’s exact test for binary data and Mann-Whitney U test for continuous data.
Results
Twenty-three PPA subjects were diagnosed with logopenic (n=11) or nonfluent/agrammatic (n=12) aphasia. There were no significant differences in illness duration (agrammatic=3.4 years; logopenic=3.3 years) or age at onset (nonfluent/agrammatic =67.3; logopenic=62.0), but those with logopenic aphasia were more impaired on Mini-Mental State Examination (21.7/30 points vs. 26.1/30; p=0.04). In contrast, those with logopenic aphasia had fewer parkinsonian motor features than those with agrammatic aphasia (5.7/132 vs. 16.8/132; p=0.003) which was driven by bradykinesia (p=0.02) and speech facial/expression (p=0.04); less so rigidity (p=0.06). Dysarthria was more frequent in the nonfluent/agrammatic subgroup.
Conclusions
Nonfluent/agrammatic subjects have more parkinsonian motor features than logopenic subjects, likely reflecting underlying tau pathology in the agrammatic variant.
doi:10.1016/j.parkreldis.2012.04.011
PMCID: PMC3424382  PMID: 22575236
Parkinsonism; primary progressive aphasia; logopenic aphasia; agrammatic aphasia; extrapyramidal
8.  FDG PET and MRI in Logopenic Primary Progressive Aphasia versus Dementia of the Alzheimer’s Type 
PLoS ONE  2013;8(4):e62471.
Objectives
The logopenic variant of primary progressive aphasia is an atypical clinical variant of Alzheimer’s disease which is typically characterized by left temporoparietal atrophy on magnetic resonance imaging and hypometabolism on F-18 fluorodeoxyglucose positron emission tomography. We aimed to characterize and compare patterns of atrophy and hypometabolism in logopenic primary progressive aphasia, and determine which brain regions and imaging modality best differentiates logopenic primary progressive aphasia from typical dementia of the Alzheimer’s type.
Methods
A total of 27 logopenic primary progressive aphasia subjects underwent fluorodeoxyglucose positron emission tomography and volumetric magnetic resonance imaging. These subjects were matched to 27 controls and 27 subjects with dementia of the Alzheimer’s type. Patterns of atrophy and hypometabolism were assessed at the voxel and region-level using Statistical Parametric Mapping. Penalized logistic regression analysis was used to determine what combinations of regions best discriminate between groups.
Results
Atrophy and hypometabolism was observed in lateral temporoparietal and medial parietal lobes, left greater than right, and left frontal lobe in the logopenic group. The logopenic group showed greater left inferior, middle and superior lateral temporal atrophy (inferior p = 0.02; middle p = 0.007, superior p = 0.002) and hypometabolism (inferior p = 0.006, middle p = 0.002, superior p = 0.001), and less right medial temporal atrophy (p = 0.02) and hypometabolism (p<0.001), and right posterior cingulate hypometabolism (p<0.001) than dementia of the Alzheimer’s type. An age-adjusted penalized logistic model incorporating atrophy and hypometabolism achieved excellent discrimination (area under the receiver operator characteristic curve = 0.89) between logopenic and dementia of the Alzheimer’s type subjects, with optimal discrimination achieved using right medial temporal and posterior cingulate hypometabolism, left inferior, middle and superior temporal hypometabolism, and left superior temporal volume.
Conclusions
Patterns of atrophy and hypometabolism both differ between logopenic primary progressive aphasia and dementia of the Alzheimer’s type and both modalities provide excellent discrimination between groups.
doi:10.1371/journal.pone.0062471
PMCID: PMC3633885  PMID: 23626825
9.  Clinical Characterization of a Kindred with a Novel Twelve Octapeptide Repeat Insertion in the Prion Protein Gene 
Archives of Neurology  2011;68(9):1165-1170.
Objective
To report the clinical, electroencephalographic, and neuroradiologic findings in a kindred with a novel insertion in the prion protein gene (PRNP).
Design
Clinical description of a kindred.
Setting
Mayo Clinic Alzheimer’s Disease Research Center (Rochester).
Subjects
Two pathologically-confirmed cases and their relatives.
Main outcome measures
Clinical features, electroencephalographic patterns, magnetic resonance imaging abnormalities, genetic analyses and neuropathological features.
Results
The proband presented with clinical and neuroimaging features of atypical frontotemporal dementia (FTD) and ataxia. Generalized tonic-clonic seizures developed later in her course, and electroencephalography revealed spike and wave discharges but no periodic sharp wave complexes. Her affected sister and father also exhibited FTD-like features, and both experienced generalized tonic-clonic seizures and gait ataxia late in their course. Genetic analyses in the proband identified a novel defect in PRNP with one mutated allele carrying a 288 base pair insertion (BPI) consisting of 12 octapeptide repeats. Neuropathologic examination of the sister and proband revealed PrP-positive plaques and widespread tau-positive tangles.
Conclusion
This kindred has a unique combination of clinical and neuropathologic features associated with the largest BPI identified to date in PRNP, and underscores the need to consider familial prion disease in the differential diagnosis of a familial FTD-like syndrome.
doi:10.1001/archneurol.2011.187
PMCID: PMC3326586  PMID: 21911696
frontotemporal dementia; FTD; nonfluent aphasia; Gerstmann–Straüssler–Scheinker syndrome (GSS); Creutzfeldt-Jakob disease (CJD); prion; PRNP
10.  Neuropsychiatric Aspects of Primary Progressive Aphasia 
Few studies have reported neuropsychiatric symptoms (NPS) in Primary Progressive Aphasia (PPA), a neurodegenerative disorder that primarily affects the left hemisphere. Depression is associated with left-sided stroke, but it remains unclear if depression and other NPS are also associated with PPA. The authors compared the frequency of NPS in 55 cases of PPA with 110 cognitively normal persons matched for age, sex and education. Depression, apathy, agitation, anxiety, appetite change, and irritability are associated with PPA. Hallucinations, delusion and night time behavior were not associated with PPA.
doi:10.1176/appi.neuropsych.23.2.168
PMCID: PMC3204925  PMID: 21677245
11.  Characterizing a neurodegenerative syndrome: primary progressive apraxia of speech 
Brain  2012;135(5):1522-1536.
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.
doi:10.1093/brain/aws032
PMCID: PMC3338923  PMID: 22382356
primary progressive apraxia of speech; apraxia of speech; primary progressive aphasia; voxel-based morphometry; diffusion tensor imaging; fluorodeoxyglucose; Pittsburg compound B; supplementary motor area
12.  Posterior Localization of Dynein and Dorsal-Ventral Axis Formation Depend on Kinesin in Drosophila Oocytes 
Current biology : CB  2002;12(17):1541-1545.
Summary
To establish the major body axes, late Drosophila oocytes localize determinants to discrete cortical positions: bicoid mRNA to the anterior cortex, oskar mRNA to the posterior cortex, and gurken mRNA to the margin of the anterior cortex adjacent to the oocyte nucleus (the “anterodorsal corner”) [1–3]. These localizations depend on microtubules [4–7] that are thought to be organized such that plus end-directed motors can move cargoes, like oskar, away from the anterior/lateral surfaces and hence toward the posterior pole [8–10]. Likewise, minus end-directed motors may move cargoes toward anterior destinations [6, 11–13]. Contradicting this, cytoplasmic dynein, a minus-end motor, accumulates at the posterior [14]. Here, we report that disruption of the plus-end motor kinesin I causes a shift of dynein from posterior to anterior. This provides an explanation for the dynein paradox, suggesting that dynein is moved as a cargo toward the posterior pole by kinesin-generated forces. However, other results present a new transport polarity puzzle. Disruption of kinesin I causes partial defects in anterior positioning of the nucleus and severe defects in anterodorsal localization of gurken mRNA. Kinesin may generate anterodorsal forces directly, despite the apparent preponderance of minus ends at the anterior cortex. Alternatively, kinesin I may facilitate cytoplasmic dynein-based anterodorsal forces by repositioning dynein toward microtubule plus ends.
PMCID: PMC3209760  PMID: 12225672
13.  Statistical Models of F2 Slope in Relation to Severity of Dysarthria 
Folia Phoniatrica et Logopaedica  2009;61(6):329-335.
Objective
This study investigated the distribution of second-formant (F2) slopes in a relatively large number of speakers with dysarthria associated with two different underlying diseases.
Patients and Methods
Forty speakers with dysarthria (20 with Parkinson's disease, PD; 20 with stroke) and 5 control speakers without a history of neurological disease were asked to repeat six words (coat, hail, sigh, shoot, row and wax) 10 times. Acoustic analysis was performed to derive F2 slope, and speech intelligibility data were collected using a direct magnitude estimate technique to examine its relationship to F2 slope.
Results
Statistical analysis revealed that both clinical groups showed significantly reduced F2 slopes compared to healthy speakers for all words but row. No group difference was found between speakers with PD and stroke; however, different words showed varying sensitivity to the speech motor control problems. The F2 slopes of only two words, shoot and wax, were significantly correlated with scaled speech intelligibility.
Conclusion
The findings support the idea that distributional characteristics of acoustic variables, such as F2 slope, could be used to develop a quantitative metric of severity of speech motor control deficits in dysarthria, when the materials are appropriately selected and additional distributional characteristics are studied.
doi:10.1159/000252849
PMCID: PMC2855272  PMID: 19864914
Acoustic analysis; Dysarthria; Speech intelligibility
14.  Very Early Semantic Dementia With Progressive Left≫Right Temporal Lobe Atrophy: An Eight-Year Longitudinal Study 
Archives of neurology  2008;65(12):1659-1663.
Background
Semantic dementia (SD) is a syndrome within the spectrum of frontotemporal lobar degenerations (FTLD) characterized by fluent progressive aphasia (particularly anomia) and loss of word meaning.
Objective
To report a unique case of very early semantic dementia with slowly progressive course allowing insights into the early natural history of this disorder.
Design
Case report.
Setting
Tertiary care university hospital and academic center.
Patient
A 62-year-old female retired teacher presenting with “memory” complaints.
Main Outcome Measures
Clinical course, neuropsychological data, MRI.
Results
The patient was first evaluated when standard neuropsychological measures were normal, but subtle left anterior temporal lobe atrophy was present. Over the follow-up period of eight years, she developed profound anomia and loss of word meaning associated with progressive left anterior temporal lobe atrophy consistent with semantic dementia. In more recent years, anterograde memory impairment as well as mild prosopagnosia have evolved in association with left hippocampal atrophy and subtle atrophy in the homologous gyri of the right anterior temporal lobe. She remains functionally independent despite her current deficits.
Conclusions
Early identification of patients who will develop semantic dementia is difficult and might be missed with standard clinical, neuropsychological, and structural neuroimaging evaluations. Recognition of this relatively rare syndrome is important for early diagnosis and prognostication, and particularly for therapeutic interventions in the future.
doi:10.1001/archneurol.2008.507
PMCID: PMC2902001  PMID: 19064755
frontotemporal lobar degeneration; semantic dementia; MRI; neuropsychology
15.  Progressive aphasia secondary to Alzheimer disease pathology: A clinicopathologic and MRI study 
Neurology  2008;70(1):25-34.
Background
The pathology causing progressive aphasia is typically a variant of frontotemporal lobar degeneration, especially with ubiquitin-positive-inclusions (FTLD-U). Less commonly the underlying pathology is Alzheimer disease (AD).
Objective
To compare clinicopathological and MRI features of subjects with progressive aphasia and AD pathology, to subjects with aphasia and FTLD-U pathology, and subjects with typical AD.
Methods
We identified 5 subjects with aphasia and AD pathology and 5 with aphasia and FTLD-U pathology with an MRI from a total of 216 aphasia subjects. Ten subjects with typical AD clinical features and AD pathology were also identified. All subjects with AD pathology underwent pathological re-analysis with TDP-43 immunohistochemistry. Voxel-based morphometry (VBM) was used to assess patterns of grey matter atrophy in the aphasia cases with AD pathology, aphasia cases with FTLD-U, and typical AD cases with AD pathology, compared to a normal control group.
Results
All aphasic subjects had fluent speech output. However, those with AD pathology had better processing speed than those with FTLD-U pathology. Immunohistochemistry with TDP-43 antibodies was negative. VBM revealed grey matter atrophy predominantly in the temporoparietal cortices with notable sparing of the hippocampus in the aphasia with AD subjects. In comparison, the aphasic subjects with FTLD-U showed sparing of the parietal lobe. Typical AD subjects showed temporoparietal and hippocampal atrophy.
Conclusions
A temporoparietal pattern of atrophy on MRI in patients with progressive fluent aphasia and relatively preserved processing speed is suggestive of underlying AD pathology rather than FTLD-U.
doi:10.1212/01.wnl.0000287073.12737.35
PMCID: PMC2749307  PMID: 18166704
Primary progressive aphasia; Progressive non-fluent aphasia; Logopenic progressive aphasia; frontotemporal lobar degeneration with ubiquitin-only-immunoreactive changes; Voxel based morphometry
16.  Clinicopathologic and Imaging Correlates of Progressive Aphasia and Apraxia of Speech 
Brain : a journal of neurology  2006;129(Pt 6):1385-1398.
Apraxia of speech (AOS) is a motor speech disorder characterized by slow speaking rate, abnormal prosody and distorted sound substitutions, additions, repetitions and prolongations, sometimes accompanied by groping and trial-and error articulatory movements. Although AOS is frequently subsumed under the heading of aphasia, and indeed most often co-occurs with aphasia, it can be the predominant or even the sole manifestation of a degenerative neurologic disease. In this study we determined whether the clinical classifications of aphasia and AOS correlated with pathological diagnoses and specific biochemical and anatomical structural abnormalities. Seventeen cases with initial diagnoses of a degenerative aphasia or AOS were reclassified independently by two speech-language pathologists — blinded to pathologic and biochemical findings - into one of five operationally defined categories of aphasia and AOS. Pathological diagnoses in the 17 cases were progressive supranuclear palsy in six, corticobasal degeneration in five, frontotemporal lobar degeneration with ubiquitin-only-immunoreactive changes in five, and Pick’s disease in one. Voxel-based morphometry and SPECT were completed, blinded to the clinical diagnoses, and clinico-imaging and clinico-pathological associations were then sought. Interjudge clinical classification reliability was 87% (κ =0.8) for all evaluations. Eleven cases had evidence of AOS, of which all (100%) had a pathological diagnosis characterized by underlying tau biochemistry, while five of the other six cases without AOS did not have tau biochemistry (p=0.001). A majority of the 17 cases had more than one yearly evaluation, demonstrating the evolution of the speech and language syndromes, as well as motor signs. Voxel-based morphometry revealed the premotor and supplemental motor cortices to be the main cortical regions associated with AOS, while the anterior peri-sylvian region was associated with non-fluent aphasia. Refining the classification of the degenerative aphasias and AOS may be necessary to improve our understanding of the relationships among behavioral, pathological, and imaging correlations.
doi:10.1093/brain/awl078
PMCID: PMC2748312  PMID: 16613895
Premotor cortex; supplementary motor cortex; progressive supranuclear palsy; apraxia of speech; aphasia
17.  Analysis of Diadochokinesis in Ataxic Dysarthria Using the Motor Speech Profile Program™ 
Aims
The Diadochokinetic Rate Analysis (DRA) in the KayPENTAX Motor Speech Profile is a computer program for the analysis of diadochokinesis (DDK). The objective of this study is to evaluate the suitability, reliability, and concurrent validity of the results from the DRA protocol and hand measurement for individuals with ataxic dysarthria, which is characteristically associated with dysdiadochokinesis.
Methods
Twenty-one participants with ataxic dysarthria were recorded as they repeated various syllables as quickly and steadily as possible. The DDK samples were executed by the DRA protocol at different thresholds and were also hand-measured. Analyses were based on the percentage of nonexecutable DDK samples, defined as samples in which the lowest peak intensity during CV syllables is lower than the highest peak intensity during intersyllable pauses, and the comparisons of the results between repeated analyses at different thresholds and between automatic and manual measuring methods.
Results
(1) More than one third of the DDK samples were nonexecutable; (2) the reliability at different thresholds and concurrent validity between different measuring methods were both satisfactory, and (3) temporal variation parameters were more inconsistent between different measuring methods than intensity variation parameters.
Conclusion
DRA has notable limitations in its clinical application but there is a considerable potential for improving its performance.
doi:10.1159/000184539
PMCID: PMC2790744  PMID: 19088478
Diadochokinesis; Reliability; Validity
18.  A Function for Kinesin I in the Posterior Transport of oskar mRNA and Staufen Protein 
Science (New York, N.Y.)  2000;289(5487):2120-2122.
The asymmetric localization of messenger RNA (mRNA) and protein determinants plays an important role in the establishment of complex body plans. In Drosophila oocytes, the anterior localization of bicoid mRNA and the posterior localization of oskar mRNA are key events in establishing the anterior-posterior axis. Although the mechanisms that drive bicoid and oskar localization have been elusive, oocyte microtubules are known to be essential. Here we report that the plus end–directed microtubule motor kinesin I is required for the posterior localization of oskar mRNA and an associated protein, Staufen, but not for the anterior-posterior localization of other asymmetric factors. Thus, a complex containing oskar mRNA and Staufen may be transported along microtubules to the posterior pole by kinesin I.
PMCID: PMC1764218  PMID: 11000113

Results 1-18 (18)