Facilitating text reading in posterior cortical atrophy

Objective We report 1) the first quantitative investigation of text reading in posterior cortical atrophy (PCA); and 2) the effects of two novel software-based reading aids that result in dramatic improvements in PCA patients' reading ability. Methods Reading performance, eye movements and fixations were assessed in PCA and typical Alzheimer’s disease (tAD) patients and healthy controls (Experiment 1). Two reading aids (single- and double-word) were evaluated based on the notion that reducing the spatial and oculomotor demands of text reading might support reading in PCA (Experiment 2). Results PCA patients’ mean reading accuracy was significantly worse (57%) compared to both tAD patients (98%) and healthy controls (99%); spatial aspects of passages were the primary determinants of text reading ability in PCA. Both aids led to considerable gains in reading accuracy (PCA mean reading accuracy: single-word reading aid = 96%; individual patient improvement range: 6%-270%) and self-rated measures of reading. Data suggest a greater efficiency of PCA patients’ fixations and eye movements under the single-word reading aid. Conclusions These findings demonstrate how neurological characterisation of a neurodegenerative syndrome (PCA) and detailed cognitive analysis of an important everyday skill (reading) can combine to yield aids capable of supporting important everyday functional abilities. Classification of evidence This study provides Class III evidence that for patients with posterior cortical atrophy, two software-based reading aids (single-word and double-word) improve reading accuracy

Looking but Not Seeing: Recent Perspectives on Posterior Cortical Atrophy

Posterior cortical atrophy (PCA) is the canonical “visual dementia,” with affected individuals experiencing a progressive disintegration of their visual world owing to dysfunction and atrophy at the back of the brain. The syndrome, which also affects literacy, numeracy, and gesture, is typically caused by Alzheimer’s disease, but is distinguished from more common amnestic presentations by virtue of relatively preserved episodic memory and insight. Although problems with object and space perception are the most widely reported and investigated symptoms, these higher-order perceptual difficulties are often underpinned by an array of changes in more basic visual and oculomotor processes. Here we review recent studies providing insights into these more elementary aspects of vision in PCA, including fixation stability, saccade generation, point localization, excessive crowding, and factors affecting the effective field of vision. We argue that a more detailed appreciation of these fundamental changes in the early visual system not only will improve the characterization and understanding of this rare clinico-radiological syndrome but will also guide the design of visual aids and strategies aimed at maintaining everyday abilities in individuals with PCA

Neuropsychology, eye tracking and neuroimaging perspectives on Posterior Cortical Atrophy

This thesis describes investigations of the clinico-radiological syndrome Posterior Cortical Atrophy, addressing two broad themes: the consequences of PCA for everyday activities (particularly scene perception) and the heterogeneity of symptoms in PCA. Despite improvements in the recognition and characterisation of PCA, we have little understanding of what the world looks like to someone with PCA. This thesis investigates patients’ perception of real-world stimuli (scenes) using a number of methodologies; characterising their response times when categorising scenes and giving a novel qualitative report of patients’ verbal descriptions (Chapter 2). It is possible that oculomotor behaviour is a contributory factor in these tasks, therefore a study of fixation, saccades and smooth pursuit was carried out. This characterised in detail for the first time the oculomotor abnormalities present in PCA (Chapter 3), facilitating further investigation of patients’ eye movements when viewing scenes (Chapters 4 and 5), revealing a striking impairment in the ability to change fixation patterns in response to task demands. The consequences of PCA for everyday activities are also investigated through a questionnaire given to carers allowing a wide range of symptoms and behaviours to be investigated over different stages of disease severity (Chapter 6). The range of symptoms and severity that this questionnaire measures will eventually allow better characterisation of the heterogeneity within PCA, and the early onset Alzheimer’s Disease spectrum more broadly. One specific manifestation of this heterogeneity is investigated in Chapter 7, demonstrating that a proportion of PCA patients show asymmetric motor symptoms (myoclonus and limb rigidity on the left side) associated with atrophy of motor cortex in the right hemisphere. Together, these studies improve our knowledge of the consequences of PCA for scene perception and more general everyday activities, and address aspects of heterogeneity in the syndrome; with implications for interventions to improve diagnosis and clinical management

The oral spelling profile of Posterior Cortical Atrophy and the nature of the graphemic representation

Spelling is a complex cognitive task where central and peripheral components are involved in engaging resources from many different cognitive processes. The present paper aims to both characterize the oral spelling deficit in a population of patients affected by a neurodegenerative condition and to clarify the nature of the graphemic representation within the currently available spelling models. Indeed, the nature of graphemic representation as a linear or multi-componential structure is still debated. Different hypotheses have been raised about its nature in the orthographic lexicon, with one positing that graphemes are complex objects whereby quantity and identity are separately represented in orthographic representations and can thus be selectively impaired. Posterior cortical atrophy (PCA) is a neurodegenerative condition that mainly affects visuoperceptual and visuospatial functions. Spelling impairments are considered part of the disease. Nonetheless the spelling deficit has received little attention so far and often it has been interpreted in relation to peripheral impairments such as writing difficulties associated with visuoperceptual and visuospatial deficits. In the present study we provide a detailed characterization of the oral spelling profile in PCA. The data suggest that multiple deficits underpin oral spelling problems in PCA, with elements of surface and phonological dysgraphia but also suggesting the involvement of the graphemic buffer. A large phenotypic individual variability is reported. Moreover, the larger proportion and the specific nature of errors involving geminate (i.e., double) as compared to non-geminate (i.e., non-double) letters suggest that a further central impairment might be associated with the abstract graphemic representation of letter numerosity. The present study contributes to the clinical characterization of PCA and to the current debate in the cognitive literature on spelling models. Findings despite not definitive, support the hypothesis that graphemic representations are multidimensional mental objects that separately encode information about grapheme identity and quantity

Synthesis and structures of polyiodide radical cation salts of donors combining tetrathiafulvalene with multiple thiophene or oligo-thiophene substituents

A series of TTF and EDT-TTF derived donors bearing thiophene, bithiophene and terthiophene side chains is described, from which a group of six radical cation salts with polyiodide ions were formed and structurally characterised. Typically, they contain complex networks of pentaiodide or triiodide anions or both, in some cases including further iodine, with networks of eight, ten, twelve or sixteen iodine atoms. Donor monocations form face-to-face pairs, but tetrakis-substituted donors are slipped along their main axis so the donor side chains can wrap around each other

Pronounced Impairment of Everyday Skills and Self-Care in Posterior Cortical Atrophy.

Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by progressive visual dysfunction and parietal, occipital, and occipitotemporal atrophy. The aim of this study was to compare the impact of PCA and typical Alzheimer's disease (tAD) on everyday functional abilities and neuropsychiatric status. The Cambridge Behavioural Inventory-Revised was given to carers of 32 PCA and 71 tAD patients. PCA patients showed significantly greater impairment in everyday skills and self-care while the tAD group showed greater impairment in aspects of memory and orientation, and motivation. We suggest that PCA poses specific challenges for those caring for people affected by the condition

Physiological phenotyping of dementias using emotional sounds.

INTRODUCTION: Emotional behavioral disturbances are hallmarks of many dementias but their pathophysiology is poorly understood. Here we addressed this issue using the paradigm of emotionally salient sounds. METHODS: Pupil responses and affective valence ratings for nonverbal sounds of varying emotional salience were assessed in patients with behavioral variant frontotemporal dementia (bvFTD) (n = 14), semantic dementia (SD) (n = 10), progressive nonfluent aphasia (PNFA) (n = 12), and AD (n = 10) versus healthy age-matched individuals (n = 26). RESULTS: Referenced to healthy individuals, overall autonomic reactivity to sound was normal in Alzheimer's disease (AD) but reduced in other syndromes. Patients with bvFTD, SD, and AD showed altered coupling between pupillary and affective behavioral responses to emotionally salient sounds. DISCUSSION: Emotional sounds are a useful model system for analyzing how dementias affect the processing of salient environmental signals, with implications for defining pathophysiological mechanisms and novel biomarker development

(Con)text-specific effects of visual dysfunction on reading in posterior cortical atrophy.

Reading deficits are a common early feature of the degenerative syndrome posterior cortical atrophy (PCA) but are poorly understood even at the single word level. The current study evaluated the reading accuracy and speed of 26 PCA patients, 17 typical Alzheimer's disease (tAD) patients and 14 healthy controls on a corpus of 192 single words in which the following perceptual properties were manipulated systematically: inter-letter spacing, font size, length, font type, case and confusability. PCA reading was significantly less accurate and slower than tAD patients and controls, with performance significantly adversely affected by increased letter spacing, size, length and font (cursive < non-cursive), and characterised by visual errors (69% of all error responses). By contrast, tAD and control accuracy rates were at or near ceiling, letter spacing was the only perceptual factor to influence reading speed in the same direction as controls, and, in contrast to PCA patients, control reading was faster for larger font sizes. The inverse size effect in PCA (less accurate reading of large than small font size print) was associated with lower grey matter volume in the right superior parietal lobule. Reading accuracy was associated with impairments of early visual (especially crowding), visuoperceptual and visuospatial processes. However, these deficits were not causally related to a universal impairment of reading as some patients showed preserved reading for small, unspaced words despite grave visual deficits. Rather, the impact of specific types of visual dysfunction on reading was found to be (con)text specific, being particularly evident for large, spaced, lengthy words. These findings improve the characterisation of dyslexia in PCA, shed light on the causative and associative factors, and provide clear direction for the development of reading aids and strategies to maximise and sustain reading ability in the early stages of disease

Motor features in posterior cortical atrophy and their imaging correlates

Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by impaired higher visual processing skills; however, motor features more commonly associated with corticobasal syndrome may also occur. We investigated the frequency and clinical characteristics of motor features in 44 PCA patients and, with 30 controls, conducted voxel-based morphometry, cortical thickness, and subcortical volumetric analyses of their magnetic resonance imaging. Prominent limb rigidity was used to define a PCA-motor subgroup. A total of 30% (13) had PCA-motor; all demonstrating asymmetrical left upper limb rigidity. Limb apraxia was more frequent and asymmetrical in PCA-motor, as was myoclonus. Tremor and alien limb phenomena only occurred in this subgroup. The subgroups did not differ in neuropsychological test performance or apolipoprotein E4 allele frequency. Greater asymmetry of atrophy occurred in PCA-motor, particularly involving right frontoparietal and peri-rolandic cortices, putamen, and thalamus. The 9 patients (including 4 PCA-motor) with pathology or cerebrospinal fluid all showed evidence of Alzheimer's disease. Our data suggest that PCA patients with motor features have greater atrophy of contralateral sensorimotor areas but are still likely to have underlying Alzheimer's disease

Eyetracking Metrics in Young Onset Alzheimer’s Disease: A Window into Cognitive Visual Functions

Young onset Alzheimer’s disease (YOAD) is defined as symptom onset before the age of 65 years and is particularly associated with phenotypic heterogeneity. Atypical presentations, such as the clinic-radiological visual syndrome posterior cortical atrophy (PCA), often lead to delays in accurate diagnosis. Eyetracking has been used to demonstrate basic oculomotor impairments in individuals with dementia. In the present study, we aim to explore the relationship between eyetracking metrics and standard tests of visual cognition in individuals with YOAD. Fifty-seven participants were included: 36 individuals with YOAD (n =  26 typical AD; n =  10 PCA) and 21 age-matched healthy controls. Participants completed three eyetracking experiments: fixation, pro-saccade, and smooth pursuit tasks. Summary metrics were used as outcome measures and their predictive value explored looking at correlations with visuoperceptual and visuospatial metrics. Significant correlations between eyetracking metrics and standard visual cognitive estimates are reported. A machine-learning approach using a classification method based on the smooth pursuit raw eyetracking data discriminates with approximately 95% accuracy patients and controls in cross-validation tests. Results suggest that the eyetracking paradigms of a relatively simple and specific nature provide measures not only reflecting basic oculomotor characteristics but also predicting higher order visuospatial and visuoperceptual impairments. Eyetracking measures can represent extremely useful markers during the diagnostic phase and may be exploited as potential outcome measures for clinical trials