The Role of Language Severity and Education in Explaining Performance on Object and Action Naming in Primary Progressive Aphasia

Despite the common assumption that atrophy in a certain brain area would compromise the function that it subserves, this is not always the case, especially in complex clinical syndromes such as primary progressive aphasia (PPA). Clinical and demographic information may contribute to PPA phenotypes and explain the manifested impairments better than atrophy. In the present study, we asked how much variance of the object and action naming impairments observed in PPA may be attributed to atrophy in the language network alone vs. additional clinical and demographic factors including language severity and education. Thirty-nine participants with PPA underwent magnetic resonance imaging (MRI) for volumetric analysis and a complete neuropsychological examination, including standardized tests of object and action naming. We used stepwise regression models to compare atrophy (volumetric model) to clinical/demographic variables (clinical-demographic model) for naming objects and actions. The clinical-demographic model was the best-fit model that explained the largest amount of variance in both object and action naming. Brain volume measurements alone explained little variance in both object and action naming. Clinical factors, particularly language severity, and demographic factors, particularly education, need to be considered in conjunction with brain volumes in PPA. The present study emphasizes the complexity of PPA as a syndrome and provides an example of how volumetric, clinical and demographic factors may interact in determining naming performance/deterioration

Brain volumes as predictors of tDCS effects in primary progressive aphasia

The current study aims to determine the brain areas critical for response to anodal transcranial direct current stimulation (tDCS) in PPA. Anodal tDCS and sham were administered over the left inferior frontal gyrus (IFG), combined with written naming/spelling therapy. Thirty people with PPA were included in this study, and assessed immediately, 2 weeks, and 2 months post-therapy. We identified anatomical areas whose volumes significantly predicted the additional tDCS effects. For trained words, the volumes of the left Angular Gyrus and left Posterior Cingulate Cortex predicted the additional tDCS gain. For untrained words, the volumes of the left Middle Frontal Gyrus, left Supramarginal Gyrus, and right Posterior Cingulate Cortex predicted the additional tDCS gain. These findings show that areas involved in language, attention and working memory contribute to the maintenance and generalization of stimulation effects. The findings highlight that tDCS possibly affects areas anatomically or functionally connected to stimulation targets

P1‐349: Advancing Clinical And Biomarker Research In Ad: The Lead Study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152716/1/alzjjalz201906904.pd

Consensus classification of posterior cortical atrophy

INTRODUCTION: A classification framework for posterior cortical atrophy (PCA) is proposed to improve the uniformity of definition of the syndrome in a variety of research settings. METHODS: Consensus statements about PCA were developed through a detailed literature review, the formation of an international multidisciplinary working party which convened on four occasions, and a Web-based quantitative survey regarding symptom frequency and the conceptualization of PCA. RESULTS: A three-level classification framework for PCA is described comprising both syndrome- and disease-level descriptions. Classification level 1 (PCA) defines the core clinical, cognitive, and neuroimaging features and exclusion criteria of the clinico-radiological syndrome. Classification level 2 (PCA-pure, PCA-plus) establishes whether, in addition to the core PCA syndrome, the core features of any other neurodegenerative syndromes are present. Classification level 3 (PCA attributable to AD [PCA-AD], Lewy body disease [PCA-LBD], corticobasal degeneration [PCA-CBD], prion disease [PCA-prion]) provides a more formal determination of the underlying cause of the PCA syndrome, based on available pathophysiological biomarker evidence. The issue of additional syndrome-level descriptors is discussed in relation to the challenges of defining stages of syndrome severity and characterizing phenotypic heterogeneity within the PCA spectrum. DISCUSSION: There was strong agreement regarding the definition of the core clinico-radiological syndrome, meaning that the current consensus statement should be regarded as a refinement, development, and extension of previous single-center PCA criteria rather than any wholesale alteration or redescription of the syndrome. The framework and terminology may facilitate the interpretation of research data across studies, be applicable across a broad range of research scenarios (e.g., behavioral interventions, pharmacological trials), and provide a foundation for future collaborative work

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

The epidemiology of frontotemporal dementia.

Frontotemporal dementia, a heterogeneous neurodegenerative disorder, is a common cause of young onset dementia (i.e. dementia developing in midlife or earlier). The estimated point prevalence is 15-22/100,000, and incidence 2.7-4.1/100,000. Some 25% are late-life onset cases. Population studies show nearly equal distribution by gender, which contrasts with myriad clinical and neuropathology reports. FTD is frequently familial and hereditary; five genetic loci for causal mutations have been identified, all showing 100% penetrance. Non-genetic risk factors are yet to be identified. FTD shows poor life expectancy but with survival comparable to that of Alzheimer's disease. Recent progress includes the formulation of up-to-date diagnostic criteria for the behavioural and language variants, and the development of new and urgently needed instruments for monitoring and staging the illness. There is still need for descriptive population studies to fill gaps in our knowledge about minority groups and developing regions. More pressing, however, is the need for reliable physiological markers for disease. There is a present imperative to develop a translational science to form the conduit for transferring neurobiological discoveries and insights from bench to bedside