Longitudinal neuroanatomical and cognitive progression of posterior cortical atrophy.

Posterior cortical atrophy is a clinico-radiological syndrome characterized by progressive decline in visual processing and atrophy of posterior brain regions. With the majority of cases attributable to Alzheimer's disease and recent evidence for genetic risk factors specifically related to posterior cortical atrophy, the syndrome can provide important insights into selective vulnerability and phenotypic diversity. The present study describes the first major longitudinal investigation of posterior cortical atrophy disease progression. Three hundred and sixty-one individuals (117 posterior cortical atrophy, 106 typical Alzheimer's disease, 138 controls) fulfilling consensus criteria for posterior cortical atrophy-pure and typical Alzheimer's disease were recruited from three centres in the UK, Spain and USA. Participants underwent up to six annual assessments involving MRI scans and neuropsychological testing. We constructed longitudinal trajectories of regional brain volumes within posterior cortical atrophy and typical Alzheimer's disease using differential equation models. We compared and contrasted the order in which regional brain volumes become abnormal within posterior cortical atrophy and typical Alzheimer's disease using event-based models. We also examined trajectories of cognitive decline and the order in which different cognitive tests show abnormality using the same models. Temporally aligned trajectories for eight regions of interest revealed distinct (P < 0.002) patterns of progression in posterior cortical atrophy and typical Alzheimer's disease. Patients with posterior cortical atrophy showed early occipital and parietal atrophy, with subsequent higher rates of temporal atrophy and ventricular expansion leading to tissue loss of comparable extent later. Hippocampal, entorhinal and frontal regions underwent a lower rate of change and never approached the extent of posterior cortical involvement. Patients with typical Alzheimer's disease showed early hippocampal atrophy, with subsequent higher rates of temporal atrophy and ventricular expansion. Cognitive models showed tests sensitive to visuospatial dysfunction declined earlier in posterior cortical atrophy than typical Alzheimer's disease whilst tests sensitive to working memory impairment declined earlier in typical Alzheimer's disease than posterior cortical atrophy. These findings indicate that posterior cortical atrophy and typical Alzheimer's disease have distinct sites of onset and different profiles of spatial and temporal progression. The ordering of disease events both motivates investigation of biological factors underpinning phenotypic heterogeneity, and informs the selection of measures for clinical trials in posterior cortical atrophy.

A framework synthesis reviewing the impact of neonatal care unit admission on early caregiver-infant relationships.

AIMS: To critically review and synthesize qualitative research pertaining to the establishment of early caregiver-infant relationships in the neonatal care unit (NCU). BACKGROUND: It is well-established that bonding and attachment, established across the prenatal and early childhood periods, affect child cognitive and behavioural development. Proximity, reciprocity, and commitment are key to the formation of these early relationships. It is intuitively likely that an admission to the NCU may affect early reciprocal caregiver-infant relationships. DESIGN: A qualitative best-fit framework synthesis. DATA SOURCES: A systematic search of four databases (PsycINFO, MEDLINE, British Nursing Index and CINAHL) was conducted, from January 2000-December 2018. REVIEW METHODS: The RATS quality appraisal tool was used to evaluate study quality. To ensure reliability, 20% of studies were randomly selected for independent rating. A "best-fit" synthesis approach using an existing framework of early parent-infant attachment and bonding was adopted to synthesize the review findings. FINDINGS: Twenty studies, from an original 3,526 unique articles, were included in the review. Studies varied in the extent to which they demonstrated transparency of procedures and in the quality of recruitment information provided. The meta-synthesis demonstrated that proximity, reciprocity, and commitment were affected by admission to a NCU and identified that parental reflections on bonding and the role of staff in this process, were important factors to consider. CONCLUSIONS: Caregiver-infant relationships are affected by admission to the NCU. The review theoretically supports moves to Family Integrated Care. Units should evaluate caregiver emotional state and consider the role of peer support. IMPACT: The synthesis revealed that areas typically implicated in the formation of attachment and bonds were affected by admission to a NCU. Results have implications on the clinical care delivered as part of neonatal care.

Prominent effects and neural correlates of visual crowding in a neurodegenerative disease population.

Crowding is a breakdown in the ability to identify objects in clutter, and is a major constraint on object recognition. Crowding particularly impairs object perception in peripheral, amblyopic and possibly developing vision. Here we argue that crowding is also a critical factor limiting object perception in central vision of individuals with neurodegeneration of the occipital cortices. In the current study, individuals with posterior cortical atrophy (n=26), typical Alzheimer's disease (n=17) and healthy control subjects (n=14) completed centrally-presented tests of letter identification under six different flanking conditions (unflanked, and with letter, shape, number, same polarity and reverse polarity flankers) with two different target-flanker spacings (condensed, spaced). Patients with posterior cortical atrophy were significantly less accurate and slower to identify targets in the condensed than spaced condition even when the target letters were surrounded by flankers of a different category. Importantly, this spacing effect was observed for same, but not reverse, polarity flankers. The difference in accuracy between spaced and condensed stimuli was significantly associated with lower grey matter volume in the right collateral sulcus, in a region lying between the fusiform and lingual gyri. Detailed error analysis also revealed that similarity between the error response and the averaged target and flanker stimuli (but not individual target or flanker stimuli) was a significant predictor of error rate, more consistent with averaging than substitution accounts of crowding. Our findings suggest that crowding in posterior cortical atrophy can be regarded as a pre-attentive process that uses averaging to regularize the pathologically noisy representation of letter feature position in central vision. These results also help to clarify the cortical localization of feature integration components of crowding. More broadly, we suggest that posterior cortical atrophy provides a neurodegenerative disease model for exploring the basis of crowding. These data have significant implications for patients with, or who will go on to develop, dementia-related visual impairment, in whom acquired excessive crowding likely contributes to deficits in word, object, face and scene perception.

Assessing the relationship between eating disorder psychopathology and autistic traits in a non-clinical adult population.

PURPOSE: Previous research demonstrates a genetic and behavioural link between eating disorders and autism spectrum disorders, and a recent study (Coombs et al. in Br J Clin Psychol 50:326-338, 2011) extends this link to typical populations, showing a positive correlation between behaviours in typically developing children. The purpose of the present study was to examine whether this relationship continues beyond development, by studying the link between behaviours in a non-clinical adult population. METHODS: We examined associations between performance on measures relating to autistic traits and disordered eating. Undergraduate students, equally balanced by gender and by subject studied (i.e. humanity or science), completed three tasks: to measure autistic traits, participants were administered the Embedded Figures Test (EFT) and the Autism-Spectrum Quotient (AQ). Eating disorder symptomatology was measured by the Eating Attitudes Test (Eat-26). RESULTS: Our data revealed a significant positive correlation between scores on the AQ and Eat-26. Multiple linear regressions showed that higher scores on the AQ were particularly associated with higher scores on the Bulimia & Food Preoccupation subscale of the Eat-26. EFT performance was positively related to behaviours associated with autism and eating disorders, although not reliably so. CONCLUSIONS: These data support the broader link between autistic traits and disordered eating in the non-clinical population, and demonstrate that it extends into adulthood (a time at which autistic behaviours can decrease). This work carries implications for the development of cognitive therapies for people with eating disorders.

Exploring factors which contribute to the resilience of nurses working in the neonatal care unit: A grounded theory study.

OBJECTIVES: This study aimed to produce a theoretical model to understand factors which affect the resilience of neonatal nurses. Nurses experience high levels of burnout due to the occupational stress they are exposed to. Burnout negatively affects both staff and patient outcomes, and in this population would likely affect the establishment of crucial early caregiver-infant relationships in the neonatal unit. Research suggests that increasing nurses' resilience can protect them against burnout, thus understanding factors that affect resilience in this population is critical. RESEARCH METHODOLOGY: The study adopted a constructivist grounded theory design. SETTING AND PARTICIPANTS: All participants were qualified registered nurses employed on a permanent basis in a Level 3 neonatal unit. Thirteen registered nurses attended one individual semi-structured interview. A constructivist grounded theory approach was used to analyse the subsequent verbatim transcripts. FINDINGS: The resulting model identified that individuals working as nurses in the neonatal unit function within different systemic contexts: the nursing team; the family unit; the broader neonatal team; the National Health Service and their world outside the unit. Each context presents different practical, emotional and ethical challenges. These challenges are navigated through a combination of contextual, interpersonal and intrapersonal strategies. CONCLUSIONS: The model is contextually embedded and extends existing literature pertaining to resilience of healthcare staff in other contexts. Suggestions are made in terms of adaptations to the organisational, social and individual contexts to benefit nursing resilience. Implications of the findings are also considered within the context of the ongoing Covid-19 pandemic.

Detection and localisation of hesitant steps in people with Alzheimer's disease navigating routes of varying complexity.

People with Alzheimer's disease (AD) have characteristic problems navigating everyday environments. While patients may exhibit abnormal gait parameters, adaptive gait irregularities when navigating environments are little explored or understood. The aim of this study was to assess adaptive locomotor responses of AD subjects in a complex environment requiring spatial navigation. A controlled environment of three corridors was set up: straight (I), U-shaped (U) and dog-leg (S). Participants were asked to walk along corridors as part of a counterbalanced repeated-measures design. Three groups were studied: 11 people with posterior cortical atrophy (PCA), 10 with typical Alzheimer's disease (tAD) and 13 controls. Spatio-temporal gait parameters and position within the corridors were monitored with shoe-mounted inertial measurement units (IMUs). Hesitant steps were identified from statistical analysis of the distribution of step time data. Walking paths were generated from position data calculated by double integration of IMU acceleration. People with PCA and tAD had similar gait characteristics, having shorter steps and longer step times than controls. Hesitant steps tended to be clustered within certain regions of the walking paths. IMUs enabled identification of key gait characteristics in this clinical population (step time, length and step hesitancy) and environmental conditions (route complexity) modifying their expression.

Profiles in paint: contrasting responses to a common artistic exercise by people with different dementias.

Paintings could offer insight into the varied experiences of people with different dementias. In this project, a single exercise - the painting of a group of objects in still-life - was used to capture artistic production in four artists with different diagnoses of dementia and four healthy artists. Whilst quantitative studies provide important insights into the neuroanatomical supports for artistic actions, autonomous art exercises may yield deeper understanding of the individual creative experience in the context of neurodegenerative disease.

The functional neuroanatomy of musical memory in Alzheimer's disease.

BACKGROUND: Memory for music has attracted much recent interest in Alzheimer's disease but the underlying brain mechanisms have not been defined in patients directly. Here we addressed this issue in an Alzheimer's disease cohort using activation fMRI of two core musical memory systems. METHODS: We studied 34 patients with younger onset Alzheimer's disease led either by episodic memory decline (typical Alzheimer's disease) or by visuospatial impairment (posterior cortical atrophy) in relation to 19 age-matched healthy individuals. We designed a novel fMRI paradigm based on passive listening to melodies that were either previously familiar or unfamiliar (musical semantic memory) and either presented singly or repeated (incidental musical episodic memory). RESULTS: Both syndromic groups showed significant functional neuroanatomical alterations relative to the healthy control group. For musical semantic memory, disease-associated activation group differences were localised to right inferior frontal cortex (reduced activation in the group with memory-led Alzheimer's disease); while for incidental musical episodic memory, disease-associated activation group differences were localised to precuneus and posterior cingulate cortex (abnormally enhanced activation in the syndromic groups). In post-scan behavioural testing, both patient groups had a deficit of musical episodic memory relative to healthy controls whereas musical semantic memory was unimpaired. CONCLUSIONS: Our findings define functional neuroanatomical substrates for the differential involvement of musical semantic and incidental episodic memory in major phenotypes of Alzheimer's disease. The complex dynamic profile of brain activation group differences observed suggests that musical memory may be an informative probe of neural network function in Alzheimer's disease. These findings may guide the development of future musical interventions in dementia.

Navigational cue effects in Alzheimer's disease and posterior cortical atrophy.

OBJECTIVE: Deficits in spatial navigation are characteristic and disabling features of typical Alzheimer's disease (tAD) and posterior cortical atrophy (PCA). Visual cues have been proposed to mitigate such deficits; however, there is currently little empirical evidence for their use. METHODS: The effect of visual cues on visually guided navigation was assessed within a simplified real-world setting in individuals with tAD (n = 10), PCA (n = 8), and healthy controls (n = 12). In a repeated-measures design comprising 36 trials, participants walked to a visible target destination (an open door within a built environment), with or without the presence of an obstacle. Contrast and motion-based cues were evaluated; both aimed to facilitate performance by applying perceptual changes to target destinations without carrying explicit information. The primary outcome was completion time; secondary outcomes were measures of fixation position and walking path directness during consecutive task phases, determined using mobile eyetracking and motion capture methods. RESULTS: Results illustrate marked deficits in patients' navigational ability, with patient groups taking an estimated two to three times longer to reach target destinations than controls and exhibiting tortuous walking paths. There were no significant differences between tAD and PCA task performance. Overall, patients took less time to reach target destinations under cue conditions (contrast-cue: 11.8%; 95% CI: [2.5, 20.3]) and were more likely initially to fixate on targets. INTERPRETATION: The study evaluated navigation to destinations within a real-world environment. There is evidence that introducing perceptual changes to the environment may improve patients' navigational ability.

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.

ApoE influences regional white-matter axonal density loss in Alzheimer's disease.

Mechanisms underlying phenotypic heterogeneity in young onset Alzheimer disease (YOAD) are poorly understood. We used diffusion tensor imaging and neurite orientation dispersion and density imaging (NODDI) with tract-based spatial statistics to investigate apolipoprotein (APOE) ε4 modulation of white-matter damage in 37 patients with YOAD (22, 59% APOE ε4 positive) and 23 age-matched controls. Correlation between neurite density index (NDI) and neuropsychological performance was assessed in 4 white-matter regions of interest. White-matter disruption was more widespread in ε4+ individuals but more focal (posterior predominant) in the absence of an ε4 allele. NODDI metrics indicate fractional anisotropy changes are underpinned by combinations of axonal loss and morphological change. Regional NDI in parieto-occipital white matter correlated with visual object and spatial perception battery performance (right and left, both p = 0.02), and performance (nonverbal) intelligence (WASI matrices, right, p = 0.04). NODDI provides tissue-specific microstructural metrics of white-matter tract damage in YOAD, including NDI which correlates with focal cognitive deficits, and APOEε4 status is associated with different patterns of white-matter neurodegeneration.

Processing emotion from abstract art in frontotemporal lobar degeneration.

art may signal emotions independently of a biological or social carrier: it might therefore constitute a test case for defining brain mechanisms of generic emotion decoding and the impact of disease states on those mechanisms. This is potentially of particular relevance to diseases in the frontotemporal lobar degeneration (FTLD) spectrum. These diseases are often led by emotional impairment despite retained or enhanced artistic interest in at least some patients. However, the processing of emotion from art has not been studied systematically in FTLD. Here we addressed this issue using a novel emotional valence matching task on abstract paintings in patients representing major syndromes of FTLD (behavioural variant frontotemporal dementia, n=11; sematic variant primary progressive aphasia (svPPA), n=7; nonfluent variant primary progressive aphasia (nfvPPA), n=6) relative to healthy older individuals (n=39). Performance on art emotion valence matching was compared between groups taking account of perceptual matching performance and assessed in relation to facial emotion matching using customised control tasks. Neuroanatomical correlates of art emotion processing were assessed using voxel-based morphometry of patients' brain MR images. All patient groups had a deficit of art emotion processing relative to healthy controls; there were no significant interactions between syndromic group and emotion modality. Poorer art emotion valence matching performance was associated with reduced grey matter volume in right lateral occopitotemporal cortex in proximity to regions previously implicated in the processing of dynamic visual signals. Our findings suggest that abstract art may be a useful model system for investigating mechanisms of generic emotion decoding and aesthetic processing in neurodegenerative diseases.

Locomotion and eye behaviour under controlled environment in individuals with Alzheimer's disease.

This study aimed to examine simple locomotion and eye behaviour of individuals with Posterior Cortical Atrophy (PCA) and typical Alzheimer's disease (tAD) within a simulated real-world environment. Posterior cortical atrophy (PCA) is a neurodegenerative condition characterised by parietal, occipital and occipito-temporal tissue loss and progressive impairment of higher-order visual function in contrast to relatively spared memory and language. Targeted types of locomotion were walking in a series of corridors, up or down stairs, and across an open room with or without the presence of an obstacle. Eye tracking measures and inertial moment units (IMU) were used in this experiment, and resultant acceleration of left foot and fixation duration were extracted. Findings from three participants are presented as a case series: one control, one PCA and one tAD patient. The averaged resultant acceleration of PCA patient was the slowest in all types of locomotion, especially in stairs. The averaged resultant accelerations of PCA and tAD participants were slower than the control participant. The PCA participant had longer mean fixation durations than the tAD and control participants, however, mean fixation duration was similar between tAD and control participants. Results may help characterise locomotion and eye behaviour in PCA and tAD and may suggest ways to support effective diagnosis and assessment of disease progression.