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Executive dysfunction contributes to verbal encoding and retrieval deficits in posterior cortical atrophy.

ABSTRACT: Posterior Cortical Atrophy (PCA) is a neurodegenerative syndrome that typically presents with predominant visual and spatial impairments. The early diagnostic criteria specify a relative sparing of functioning in other cognitive domains, including executive functions, language, and episodic memory, yet little is known of the cognitive profile of PCA as the disease progresses. Studies of healthy adults and other posterior cortical lesion patients implicate posterior parietal and temporal regions in executive functions of working memory and verbal fluency, both of which may impact episodic memory. Relatively little has been reported about these cognitive functions in PCA, and to our knowledge there has not yet been a study of the impact of such deficits on memory function in PCA. We sought to examine PCA patients' performance on tests of executive function and the associations to verbal episodic memory encoding, storage, and delayed recall. Nineteen individuals with PCA underwent neuropsychological and neuroimaging evaluations as part of a comprehensive clinical assessment. We developed a novel consensus rating method-the Neuropsychological Assessment Rating (NAR) scale-to grade the severity of test performance impairments in selected cognitive domains and subdomains. Hypothesis-driven analyses demonstrated relative deficits in working memory and lexical-semantic retrieval. Preliminary analyses suggested associations between both deficits and atrophy in the left-hemisphere inferior parietal lobule. These executive deficits were also associated with impairments in verbal encoding and delayed recall, but not with recognition discriminability. We conclude that deficits in verbal executive functions impact verbal episodic memory in PCA. Our findings also support theories emphasizing the role of the posterior parietal cortex in supporting executive and lexical-semantic contributions to verbal episodic memory.

SUBMITTER: Putcha D

PROVIDER: S-EPMC6120771 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Executive dysfunction contributes to verbal encoding and retrieval deficits in posterior cortical atrophy.

Putcha Deepti D McGinnis Scott M SM Brickhouse Michael M Wong Bonnie B Sherman Janet C JC Dickerson Bradford C BC

Cortex; a journal devoted to the study of the nervous system and behavior 20180510

Posterior Cortical Atrophy (PCA) is a neurodegenerative syndrome that typically presents with predominant visual and spatial impairments. The early diagnostic criteria specify a relative sparing of functioning in other cognitive domains, including executive functions, language, and episodic memory, yet little is known of the cognitive profile of PCA as the disease progresses. Studies of healthy adults and other posterior cortical lesion patients implicate posterior parietal and temporal regions ...[more]

PMID: 29864594

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Project description:Posterior cortical atrophy (PCA), usually an atypical clinical syndrome of Alzheimer's disease, has well-characterized patterns of cortical atrophy and tau deposition that are distinct from typical amnestic presentations of Alzheimer's disease. However, the mechanisms underlying the cortical spread of tau in PCA remain unclear. Here, in a sample of 17 biomarker-confirmed (A+/T+/N+) individuals with PCA, we sought to identify functional networks with heightened vulnerability to tau pathology by examining the cortical distribution of elevated tau as measured by 18F-flortaucipir (FTP) PET. We then assessed the relationship between network-specific FTP uptake and visuospatial cognitive task performance. As predicted, we found consistent and prominent localization of tau pathology in the dorsal attention network and visual network of the cerebral cortex. Elevated FTP uptake within the dorsal attention network (particularly the ratio of FTP uptake between the anterior and posterior nodes) was associated with poorer visuospatial attention in PCA; associations were also identified in other functional networks, although to a weaker degree. Furthermore, using functional MRI data collected from each patient at wakeful rest, we found that a greater anterior-to-posterior ratio in FTP uptake was associated with stronger intrinsic functional connectivity between anterior and posterior nodes of the dorsal attention network. Taken together, we conclude that our cross-sectional marker of anterior-to-posterior FTP ratio could indicate tau propagation from posterior to anterior dorsal attention network nodes, and that this anterior progression occurs in relation to intrinsic functional connectivity within this network critical for visuospatial attention. Our findings help to clarify the spatiotemporal pattern of tau propagation in relation to visuospatial cognitive decline and highlight the key role of the dorsal attention network in the disease progression of PCA.

Project description:BackgroundPosterior cortical atrophy (PCA) is typically considered to be a visual syndrome, primarily characterised by progressive impairment of visuoperceptual and visuospatial skills. However, patients commonly describe early difficulties with word retrieval. This paper details the first systematic analysis of linguistic function in PCA. Characterising and quantifying the aphasia associated with PCA is important for clarifying diagnostic and selection criteria for clinical and research studies.Methods15 patients with PCA, seven patients with logopenic/phonological aphasia (LPA) and 18 age matched healthy participants completed a detailed battery of linguistic tests evaluating auditory input processing, repetition and working memory, lexical and grammatical comprehension, single word retrieval and fluency, and spontaneous speech.ResultsRelative to healthy controls, PCA patients exhibited language impairments across all of the domains examined, but with anomia, reduced phonemic fluency and slowed speech rate the most prominent deficits. PCA performance most closely resembled that of LPA patients on tests of auditory input processing, repetition and digit span, but was relatively stronger on tasks of comprehension and spontaneous speech.ConclusionsThe study demonstrates that in addition to the well reported degradation of vision, literacy and numeracy, PCA is characterised by progressive oral language dysfunction with prominent word retrieval difficulties. Overlap in the linguistic profiles of PCA and LPA, which are both most commonly caused by Alzheimer's disease, further emphasises the notion of a phenotypic continuum between typical and atypical manifestations of the disease. Clarifying the boundaries between Alzheimer's disease phenotypes has important implications for diagnosis, clinical trial recruitment and investigations into biological factors driving phenotypic heterogeneity in Alzheimer's disease. Rehabilitation strategies to ameliorate the phonological deficit in PCA are required.

Project description:ObjectiveTo determine whether atrophy relates to phenotypical variants of posterior cortical atrophy (PCA) recently proposed in clinical criteria (i.e., dorsal, ventral, dominant-parietal, and caudal) we assessed associations between latent atrophy factors and cognition.MethodsWe employed a data-driven Bayesian modeling framework based on latent Dirichlet allocation to identify latent atrophy factors in a multicenter cohort of 119 individuals with PCA (age 64 ± 7 years, 38% male, Mini-Mental State Examination 21 ± 5, 71% β-amyloid positive, 29% β-amyloid status unknown). The model uses standardized gray matter density images as input (adjusted for age, sex, intracranial volume, MRI scanner field strength, and whole-brain gray matter volume) and provides voxelwise probabilistic maps for a predetermined number of atrophy factors, allowing every individual to express each factor to a degree without a priori classification. Individual factor expressions were correlated to 4 PCA-specific cognitive domains (object perception, space perception, nonvisual/parietal functions, and primary visual processing) using general linear models.ResultsThe model revealed 4 distinct yet partially overlapping atrophy factors: right-dorsal, right-ventral, left-ventral, and limbic. We found that object perception and primary visual processing were associated with atrophy that predominantly reflects the right-ventral factor. Furthermore, space perception was associated with atrophy that predominantly represents the right-dorsal and right-ventral factors. However, individual participant profiles revealed that the large majority expressed multiple atrophy factors and had mixed clinical profiles with impairments across multiple domains, rather than displaying a discrete clinical-radiologic phenotype.ConclusionOur results indicate that specific brain behavior networks are vulnerable in PCA, but most individuals display a constellation of affected brain regions and symptoms, indicating that classification into 4 mutually exclusive variants is unlikely to be clinically useful.

Project description:ObjectivesTo investigate the global cortical and regional quantitative features of cortical neural architecture in the brains of patients with posterior cortical atrophy (PCA) and typical Alzheimer's disease (tAD) compared with elderly healthy controls (HC).MethodsA novel diffusion MRI method, that has been shown to correlate with minicolumnar organization changes in the cerebral cortex, was used as a surrogate of neuropathological changes in dementia. A cohort of 15 PCA patients, 23 tAD and 22 healthy elderly controls (HC) were enrolled to investigate the changes in cortical diffusivity among groups. For each subject, 3 T MRI T1-weighted images and diffusion tensor imaging (DTI) scans were analysed to extract novel cortical DTI derived measures (AngleR, PerpPD and ParlPD). Receiver operating characteristics (ROC) curve analysis and the area under the curve (AUC) were used to assess the group discrimination capability of the method.ResultsThe results showed that the global cortical DTI derived measures were able to detect differences, in both PCA and tAD patients compared to healthy controls. The AngleR was the best measure to discriminate HC from tAD (AUC?=?0.922), while PerpPD was the best measure to discriminate HC from PCA (AUC?=?0.961). Finally, the best global measure to differentiate the two patient groups was ParlPD (AUC?=?0.771). The comparison between PCA and tAD patients revealed a different pattern of damage within the AD spectrum and the regional comparisons identified significant differences in key regions including parietal and temporal lobe cortical areas. The best AUCs were shown by PerpPD right lingual cortex (AUC?=?0.856), PerpPD right superior parietal cortex (AUC?=?0.842) and ParlPD right lateral occipital cortex (AUC?=?0.826).ConclusionsDiagnostic group differences were found, suggesting that the new cortical DTI analysis method may be useful to investigate cortical changes in dementia, providing better characterization of neurodegeneration, and potentially aiding differential diagnosis and prognostic accuracy.

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Executive dysfunction contributes to verbal encoding and retrieval deficits in posterior cortical atrophy.

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Executive dysfunction contributes to verbal encoding and retrieval deficits in posterior cortical atrophy.

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