There is a growing body of literature examining the utility of behavioral treatment in primary progressive aphasia (PPA). There are, however, no studies exploring treatment approaches to improve speech production in individuals with apraxia of speech (AOS) associated with the nonfluent variant of PPA. The purpose of this study was to examine a novel approach to treatment of AOS in nonfluent PPA. We implemented a treatment method using structured oral reading as a tool for improving production of multisyllabic words in an individual with mild AOS and nonfluent variant PPA. Our participant showed a reduction in speech errors during reading of novel text that was maintained at one year post-treatment. Generalization of improved speech production was observed on repetition of words and sentences and the participant showed stability of speech production over time in connected speech. Results suggest that oral reading treatment is an efficient and effective means of addressing multisyllabic word production in AOS associated with nonfluent PPA, with lasting and generalized treatment effects.

Individuals with primary progressive aphasia (PPA) suffer a gradual decline in communication ability as a result of neurodegenerative disease. Language treatment shows promise as a means of addressing these difficulties but much remains to be learned with regard to the potential value of treatment across variants and stages of the disorder. We present two cases, one with semantic variant of PPA and the other with logopenic PPA, each of whom underwent treatment that was unique in its focus on training self-cueing strategies to engage residual language skills. Despite differing language profiles and levels of aphasia severity, each individual benefited from treatment and showed maintenance of gains as well as generalization to untrained lexical items. These cases highlight the potential for treatment to capitalize on spared cognitive and neural systems in individuals with PPA, improving current language function as well as potentially preserving targeted skills in the face of disease progression.

Determining the relative contribution of amyloid plaques and neurofibrillary tangles to brain dysfunction in Alzheimer disease is critical for therapeutic approaches, but until recently could only be assessed at autopsy. We report a patient with posterior cortical atrophy (visual variant of Alzheimer disease) who was studied using the novel tau tracer [18F]AV-1451 in conjunction with [11C]Pittsburgh compound B (PIB; amyloid) and [18F]fluorodeoxyglucose (FDG) positron emission tomography. Whereas [11C]PIB bound throughout association neocortex, [18F]AV-1451 was selectively retained in posterior brain regions that were affected clinically and showed markedly reduced [18F]FDG uptake. This provides preliminary in vivo evidence that tau is more closely linked to hypometabolism and symptomatology than amyloid.

The common and specific involvement of brain networks in clinical variants of Alzheimer's disease (AD) is not well understood. We performed task-free ("resting-state") functional imaging in 60 nonfamilial AD patients, including 20 early-onset AD (age at onset <65 years, amnestic/dysexecutive deficits), 24 logopenic aphasia (language deficits), and 16 posterior cortical atrophy patients (visual deficits), as well as 60 healthy controls. Seed-based connectivity analyses were conducted to assess differences between groups in 3 default mode network (DMN) components (anterior, posterior, and ventral) and 4 additional non-DMN networks: left and right executive-control, language, and higher visual networks. Significant decreases in connectivity were found across AD variants compared with controls in the non-DMN networks. Within the DMN components, patients showed higher connectivity in the anterior DMN, in particular in logopenic aphasia. No significant differences were found for the posterior and ventral DMN. Our findings suggest that loss of functional connectivity is greatest in networks outside the DMN in early-onset and nonamnestic AD variants and may thus be a better biomarker in these patients.

© 2015 Published by Elsevier Inc.The present study investigated the pattern of longitudinal changes in cognition and anatomy in three variants of primary progressive aphasia (PPA). Eight patients with the non-fluent variant of PPA (nfvPPA), 13 patients wit

Decades of neuroscientific findings have elucidated the highly specialized brain areas involved in reading, especially along the ventral occipitotemporal stream where the critical step of recognizing words occurs. We report on a 14-year-old female with temporary dyslexia after a left ventral occipitotemporal ischemic stroke. Our longitudinal multimodal findings show that the resolution of the reading impairment was associated with heightened activity in the left posterior superior and inferior temporal gyri. Our findings highlight the role of the left inferior temporal gyrus in reading and the importance of perilesional and ipsilateral cortical areas for functional recovery after childhood stroke.

Post-mortem studies show that focal anterior temporal lobe (ATL) neurodegeneration is most often caused by frontotemporal lobar degeneration TDP-43 type C pathology. Clinically, these patients are described with different terms, such as semantic variant primary progressive aphasia (svPPA), semantic dementia (SD), or right temporal variant frontotemporal dementia (FTD) depending on whether the predominant symptoms affect language, semantic knowledge for object or people, or socio-emotional behaviors. ATL atrophy presents with various degrees of lateralization, with right-sided cases considered rarer even though estimation of their prevalence is hampered by the paucity of studies on well-characterized, pathology-proven cohorts. Moreover, it is not clear whether left and right variants show a similar distribution of atrophy within the ATL cross-sectionally and longitudinally. Here we study the largest cohort to-date of pathology-proven TDP-43-C cases diagnosed during life as svPPA, SD or right temporal variant FTD. We analyzed clinical, cognitive, and neuroimaging data from 30 cases, a subset of which was followed longitudinally. Guided by recent structural and functional parcellation studies, we constructed four bilateral ATL regions of interest (ROIs). The computation of an atrophy lateralization index allowed the comparison of atrophy patterns between the two hemispheres. This led to an automatic, imaging-based classification of the cases as left-predominant or right-predominant. We then compared the two groups in terms of regional atrophy patterns within the ATL ROIs (cross-sectionally) and atrophy progression (longitudinally). Results showed that 40% of pathology proven cases of TDP-43-C diagnosed with a temporal variant presented with right-lateralized atrophy. Moreover, the findings of our ATL ROI analysis indicated that, irrespective of atrophy lateralization, atrophy distribution within both ATLs follows a medial-to-lateral gradient. Finally, in both left and right cases, atrophy appeared to progress to the contralateral ATL, and from the anterior temporal pole to posterior temporal and orbitofrontal regions. Taken together, our findings indicate that incipient right predominant ATL atrophy is common in TDP-43-C pathology, and that distribution of damage within the ATLs appears to be the same in left- and right- sided variants. Thus, regardless of differences in clinical phenotype and atrophy lateralization, both temporal variants of FTD should be viewed as a spectrum presentation of the same disease.

There is increasing recognition of a relationship between regional variability in cerebral gyrification and neurodevelopment. Recent work in morphometric MRI has shown that the local gyrification index (lGI), a measure of regional brain folding, may be altered in certain neurodevelopmental disorders. Other studies report that the lGI generally decreases with age in adolescence and young adulthood; however, little is known about how these age-dependent differences in brain maturation occur in atypical neurodevelopment and mechanisms underlying gyrification, such as synaptic pruning. Organization and optimization of dendrites and axons connections across the brain might be driving gyrification and folding processes. In this study, we first assessed lGI differences in the left hemisphere in a cohort of 39 children with developmental dyslexia (DD) between the ages of 7 and 15 years in comparison to 56 typically developing controls (TDC). To better understand the microstructural basis of these changes, we next explored the relationship between lGI differences and cortical thickness and neurite morphology by applying neurite orientation dispersion and density imaging (NODDI). We identified significant differences in lGI between children with DD and TDC in left lateral temporal and middle frontal regions. Further, DD failed to show the expected age-related decreases in lGI in the same regions. Age-related differences in lGI in DD were not explained by differences in cortical thickness, but did correlate with NODDI neurite density and orientation dispersion index. Our findings suggest that gyrification changes in DD are related to abnormal neurite morphology, and are possibly an expression of differences in synaptic pruning.

Objective

We aimed to understand the impact of dopamine receptor D₄ (DRD₄) polymorphisms on neurodegeneration in patients with dementia. We hypothesized that DRD₄dampened-variants with reduced functional potency would be associated with greater atrophy in regions with higher receptor density. Given that DRD₄ is concentrated in anterior regions of the limbic and cortical forebrain we anticipated genotype effects in patients with a more rostral pattern of neurodegeneration.

Methods

337 subjects, including healthy controls, patients with Alzheimer's disease (AD) and frontotemporal dementia (FTD) underwent genotyping, structural MRI, and cognitive/behavioral testing. We conducted whole-brain voxel-based morphometry to examine the relationship between DRD₄ genotypes and brain atrophy patterns within and across groups. General linear modeling was used to evaluate relationships between genotype and cognitive/behavioral measures.

Results

DRD₄ dampened-variants predicted gray matter atrophy in disease-specific regions of FTD in anterior cingulate, ventromedial prefrontal, orbitofrontal and insular cortices on the right greater than the left. Genotype predicted greater apathy and repetitive motor disturbance in patients with FTD. These results covaried with frontoinsular cortical atrophy. Peak atrophy patterned along regions of neuroanatomic vulnerability in FTD-spectrum disorders. In AD subjects and controls, genotype did not impact gray matter intensity.

Conclusions

We conclude that DRD₄ polymorphisms with reduced functional potency exacerbate neuronal injury in sites of higher receptor density, which intersect with syndrome-specific regions undergoing neurodegeneration in FTD.