Exploring experiential differences in everyday activities - A focused ethnographic study in the homes of people living with memory-led Alzheimer's disease and posterior cortical atrophy.

BACKGROUND: Supporting ageing in place, quality of life and activity engagement are public health priorities for people living with dementia, but little is known about the needs and experiences of community-dwelling people with rarer forms of dementia with lesser known symptoms. Posterior cortical atrophy (PCA) is a rare form of dementia usually caused by Alzheimer's disease but which is characterised by diminished visual processing (rather than a dominant memory problem), which poses challenges for maintaining independence and accessing appropriate support. METHODS: This study used a comparative qualitative design and focussed ethnographic methods to explore experiential differences in activity engagement for 10 people with the most common, memory-led presentation of Alzheimer's disease and 10 people with posterior cortical atrophy within their everyday home environments. RESULTS: While the data collection revealed much rich variation in individual and contextual factors, some tentative high-level differences in the experiences of everyday activities could be drawn out, seemingly attributable to the different diagnoses' differing dominant symptoms. These included people with posterior cortical atrophy being less likely to use environmental cues to initiate activities, and more likely to withhold from asking for support because of preserved insight into the impact of this on carers. This lack of initiation of activities could be misinterpreted as apathy. People with posterior cortical atrophy also were discouraged from engaging in activities by disorientation within the home, and difficulties localising, identifying and manipulating objects. People with the more common, memory-led presentation of Alzheimer's disease exhibited more memory-based difficulties with engaging with activities such as forgetting planned activities, where to locate the items required for an activity and the steps involved. Despite these distinct symptom-led challenges, all participants and their family members demonstrated resourcefulness and resilience in making creative adaptations to support continued engagement in everyday activities, supporting the widely reported management strategies of people with dementia of the Alzheimer's type more generally. CONCLUSIONS: These findings offer helpful insights into some the differing impacts dementia related visual and memory impairments can have on everyday activity engagement, which will be helpful for others navigating these challenges and the health and social care practitioners working with people affected by these conditions. The findings also highlight the vast individual variation in the multitude of individual and contextual factors involved in everyday activity engagement, and suggest important areas for future work utilising methods which are similarly high in ecological validity and accessibility as the home-based focussed ethnographic methods utilised here.

Symptom-based staging for logopenic variant primary progressive aphasia.

BACKGROUND AND PURPOSE: Logopenic variant primary progressive aphasia (lvPPA) is a major variant presentation of Alzheimer's disease (AD) that signals the importance of communication dysfunction across AD phenotypes. A clinical staging system is lacking for the evolution of AD-associated communication difficulties that could guide diagnosis and care planning. Our aim was to create a symptom-based staging scheme for lvPPA, identifying functional milestones relevant to the broader AD spectrum. METHODS: An international lvPPA caregiver cohort was surveyed on symptom development under an 'exploratory' survey (34 UK caregivers). Feedback from this survey informed the development of a 'consolidation' survey (27 UK, 10 Australian caregivers) in which caregivers were presented with six provisional clinical stages and feedback was analysed using a mixed-methods approach. RESULTS: Six clinical stages were endorsed. Early symptoms included word-finding difficulty, with loss of message comprehension and speech intelligibility signalling later-stage progression. Additionally, problems with hearing in noise, memory and route-finding were prominent early non-verbal symptoms. 'Milestone' symptoms were identified that anticipate daily-life functional transitions and care needs. CONCLUSIONS: This work introduces a new symptom-based staging scheme for lvPPA, and highlights milestone symptoms that could inform future clinical scales for anticipating and managing communication dysfunction across the AD spectrum.

"I Want to Do Something" - Exploring What Makes Activities Meaningful for Community-Dwelling People Living With Dementia: A Focused Ethnographic Study.

Supporting ageing in place, quality of life, and activity engagement are public health priorities for people with dementia. The importance of maintaining opportunities for meaningful activities has been widely acknowledged for those with dementia in long-term care, but little is known about what makes activities meaningful for, and how they are experienced by, people with different types of dementia in their own homes. This study used focussed ethnographic methods to explore the motivations and meanings of everyday activity engagement within the homes of 10 people with memory-led Alzheimer's disease and 10 people with posterior cortical atrophy. While participants' interactions with their everyday environments were challenged by their diagnoses, they were all finding ways to continue meaning-making via various activities. The main findings are encapsulated in three themes: (1) The fun and the function of activities; (2) Reciprocities of care, and (3) The constitution and continuity of (a changing) self. Ongoing engagement with both fun and functional activities offered participants living with different dementias opportunities to connect with others, to offer care and support (as well as receive it), and to maintain a sense of self and identity. Implications are discussed regarding the development and delivery of tailored interventions and support to enable continued engagement in meaningful activities for people with different types of dementia living in the community.

Symptom-led staging for semantic and non-fluent/agrammatic variants of primary progressive aphasia.

INTRODUCTION: Here we set out to create a symptom-led staging system for the canonical semantic and non-fluent/agrammatic variants of primary progressive aphasia (PPA), which present unique diagnostic and management challenges not well captured by functional scales developed for Alzheimer's disease and other dementias. METHODS: An international PPA caregiver cohort was surveyed on symptom development under six provisional clinical stages and feedback was analyzed using a mixed-methods sequential explanatory design. RESULTS: Both PPA syndromes were characterized by initial communication dysfunction and non-verbal behavioral changes, with increasing syndromic convergence and functional dependency at later stages. Milestone symptoms were distilled to create a prototypical progression and severity scale of functional impairment: the PPA Progression Planning Aid ("PPA-Squared"). DISCUSSION: This work introduces a symptom-led staging scheme and functional scale for semantic and non-fluent/agrammatic variants of PPA. Our findings have implications for diagnostic and care pathway guidelines, trial design, and personalized prognosis and treatment for PPA. HIGHLIGHTS: We introduce new symptom-led perspectives on primary progressive aphasia (PPA). The focus is on non-fluent/agrammatic (nfvPPA) and semantic (svPPA) variants. Foregrounding of early and non-verbal features of PPA and clinical trajectories is featured. We introduce a symptom-led staging scheme for PPA. We propose a prototype for a functional impairment scale, the PPA Progression Planning Aid.

Revealing Individual Neuroanatomical Heterogeneity in Alzheimer Disease Using Neuroanatomical Normative Modeling.

BACKGROUND AND OBJECTIVES: Alzheimer disease (AD) is highly heterogeneous, with marked individual differences in clinical presentation and neurobiology. To explore this, we used neuroanatomical normative modeling to index regional patterns of variability in cortical thickness. We aimed to characterize individual differences and outliers in cortical thickness in patients with AD, people with mild cognitive impairment (MCI), and controls. Furthermore, we assessed the relationships between cortical thickness heterogeneity and cognitive function, ß-amyloid, phosphorylated-tau, and ApoE genotype. Finally, we examined whether cortical thickness heterogeneity was predictive of conversion from MCI to AD. METHODS: Cortical thickness measurements across 148 brain regions were obtained from T1-weighted MRI scans from 62 sites of the Alzheimer's Disease Neuroimaging Initiative. AD was determined by clinical and neuropsychological examination with no comorbidities present. Participants with MCI had reported memory complaints, and controls were cognitively normal. A neuroanatomical normative model indexed cortical thickness distributions using a separate healthy reference data set (n = 33,072), which used hierarchical Bayesian regression to predict cortical thickness per region using age and sex, while adjusting for site noise. Z-scores per region were calculated, resulting in a Z-score brain map per participant. Regions with Z-scores <-1.96 were classified as outliers. RESULTS: Patients with AD (n = 206) had a median of 12 outlier regions (out of a possible 148), with the highest proportion of outliers (47%) in the parahippocampal gyrus. For 62 regions, over 90% of these patients had cortical thicknesses within the normal range. Patients with AD had more outlier regions than people with MCI (n = 662) or controls (n = 159) (F(2, 1,022) = 95.39, p = 2.0 × 10-16). They were also more dissimilar to each other than people with MCI or controls (F(2, 1,024) = 209.42, p = 2.2 × 10-16). A greater number of outlier regions were associated with worse cognitive function, CSF protein concentrations, and an increased risk of converting from MCI to AD within 3 years (hazard ratio 1.028, 95% CI 1.016-1.039, p = 1.8 × 10-16). DISCUSSION: Individualized normative maps of cortical thickness highlight the heterogeneous effect of AD on the brain. Regional outlier estimates have the potential to be a marker of disease and could be used to track an individual's disease progression or treatment response in clinical trials.

Effects of the visual environment on object localization in posterior cortical atrophy and typical Alzheimer's disease.

Introduction: Visual processing deficits in Alzheimer's disease are associated with diminished functional independence. While environmental adaptations have been proposed to promote independence, recent guidance gives limited consideration to such deficits and offers conflicting recommendations for people with dementia. We evaluated the effects of clutter and color contrasts on performances of everyday actions in posterior cortical atrophy and memory-led typical Alzheimer's disease. Methods: 15 patients with posterior cortical atrophy, 11 with typical Alzheimer's disease and 16 healthy controls were asked to pick up a visible target object as part of two pilot repeated-measures investigations from a standing or seated position. Participants picked up the target within a controlled real-world setting under varying environmental conditions: with/without clutter, with/without color contrast cue and far/near target position. Task completion time was recorded using a target-mounted inertial measurement unit. Results: Across both experiments, difficulties locating a target object were apparent through patient groups taking an estimated 50-90% longer to pick up targets relative to controls. There was no evidence of effects of color contrast when locating objects from standing/seated positions and of any other environmental conditions from a standing position on completion time in any participant group. Locating objects, surrounded by five distractors rather than none, from a seated position was associated with a disproportionately greater effect on completion times in the posterior cortical atrophy group relative to the control or typical Alzheimer's disease groups. Smaller, not statistically significant but directionally consistent, ratios of relative effects were seen for two distractors compared with none. Discussion: Findings are consistent with inefficient object localization in posterior cortical atrophy relative to typical Alzheimer's disease and control groups, particularly with targets presented within reaching distance among visual clutter. Findings may carry implications for considering the adverse effects of visual clutter in developing and implementing environmental modifications to promote functional independence in Alzheimer's disease.

Diagnosis and Management of Posterior Cortical Atrophy.

Purpose of review: The study aims to provide a summary of recent developments for diagnosing and managing posterior cortical atrophy (PCA). We present current efforts to improve PCA characterisation and recommendations regarding use of clinical, neuropsychological and biomarker methods in PCA diagnosis and management and highlight current knowledge gaps. Recent findings: Recent multi-centre consensus recommendations provide PCA criteria with implications for different management strategies (e.g. targeting clinical features and/or disease). Studies emphasise the preponderance of primary or co-existing Alzheimer's disease (AD) pathology underpinning PCA. Evidence of approaches to manage PCA symptoms is largely derived from small studies. Summary: PCA diagnosis is frequently delayed, and people are likely to receive misdiagnoses of ocular or psychological conditions. Current treatment of PCA is symptomatic - pharmacological and non-pharmacological - and the use of most treatment options is based on small studies or expert opinion. Recommendations for non-pharmacological approaches include interdisciplinary management tailored to the PCA clinical profile - visual-spatial - rather than memory-led, predominantly young onset - and psychosocial implications. Whilst emerging disease-modifying treatments have not been tested in PCA, an accurate and timely diagnosis of PCA and determining underlying pathology is of increasing importance in the advent of disease-modifying therapies for AD and other albeit rare causes of PCA.

A cross-sectional study of memory and executive functions in patients with sporadic inclusion body myositis.

INTRODUCTION/AIMS: Sporadic inclusion body myositis (IBM) is a degenerative and inflammatory acquired myopathy characterized by muscle deposition of various proteins typically associated with Alzheimer disease and other neurodegenerative diseases. Although cognitive impairment is not noted as a clinical feature of IBM, evidence is lacking. In this study we investigated whether cognitive performance of patients with IBM differs from population norms, focusing on cognitive domains affected in early Alzheimer disease (memory, executive function), and to test whether disease duration and the level of disability of IBM are associated with cognitive function. METHODS: Twenty-four patients with IBM (mean [standard deviation]: age, 62.0 [7.2] years; disease duration, 9.6 [4.8] years) were assessed cross-sectionally on neuropsychological tests covering multiple cognitive domains, including the Preclinical Alzheimer Cognitive Composite (PACC). Performance was compared with published normative data adjusted for age, sex, and education (National Alzheimer's Coordinating Center; N = 3268). Associations were examined between PACC score, disease duration, and level of disability (assessed using the IBM Functional Rating Scale [IBMFRS]). RESULTS: Across all cognitive tests, group performance was within ±1 standard deviation of the normative mean. There was no evidence of associations between PACC score and either disease duration (ρ = -0.04, P = .87) or IBMFRS total score (ρ = 0.14, P = .52). DISCUSSION: Memory and executive function in patients with IBM did not differ from normative data, and we observed no evidence of associations between the cognitive composite and disease duration or level of disability. This addresses a question frequently asked by patients and will be of value for clinicians and patients alike.

Altered visual and haptic verticality perception in posterior cortical atrophy and Alzheimer's disease.

There is increasing theoretical and empirical support for the brain combining multisensory information to determine the direction of gravity and hence uprightness. A fundamental part of the process is the spatial transformation of sensory signals between reference frames: eye-centred, head-centred, body-centred, etc. The question 'Am I the right way up?' posed by a patient with posterior cortical atrophy (PCA) suggests disturbances in upright perception, subsequently investigated in PCA and typical Alzheimer's disease (tAD) based on what looks or feels upright. Participants repeatedly aligned to vertical a rod presented either visually (visual-vertical) or haptically (haptic-vertical). Visual-vertical involved orienting a projected rod presented without or with a visual orientation cue (circle, tilted square (±18°)). Haptic-vertical involved orientating a grasped rod with eyes closed using a combination of side (left, right) and hand (unimanual, bimanual) configurations. Intraindividual uncertainty and bias defined verticality perception. Uncertainty was consistently greater in both patient groups than in control groups, and greater in PCA than tAD. Bias in the frontal plane was strongly directionally affected by visual cue tilt (visual-vertical) and grip side (haptic-vertical). A model was developed that assumed verticality information from multiple sources is combined in a statistically optimal way to produce observed uncertainties and biases. Model results suggest the mechanism that spatially transforms graviceptive information between body parts is disturbed in both patient groups. Despite visual dysfunction being typically considered the primary feature of PCA, disturbances were greater in PCA than tAD particularly for haptic-vertical, and are considered in light of posterior parietal vulnerability. KEY POINTS: The perception of upright requires accurate and precise estimates of orientation based on multiple noisy sensory signals. The question 'Am I the right way up?' posed by a patient with posterior cortical atrophy (PCA; purported 'visual variant Alzheimer's') suggests disturbances in the perception of upright. What looks or feels upright in PCA and typical Alzheimer's disease (tAD) was investigated by asking participants to repeatedly align to vertical a rod presented visually (visual-vertical) or haptically (haptic-vertical). PCA and tAD groups exhibited not only greater perceptual uncertainty than controls, but also exaggerated bias induced by tilted visual orientation cues (visual-vertical) and grip side (haptic-vertical). When modelled, these abnormalities, which were particularly evident in PCA haptic-vertical performance, were compatible with disruption of a mechanism that spatially transforms verticality information between body parts. The findings suggest an important role of posterior parietal cortex in verticality perception, and have implications for understanding spatial disorientation in dementia.

Retinal phenotyping of variants of Alzheimer's disease using ultra-widefield retinal images.

BACKGROUND: Posterior cortical atrophy (PCA) is the most common atypical variant of Alzheimer's disease (AD). Changes associated with PCA in the brain affect the visual cortex, but little is known about retinal changes in PCA. In this study, we explored retinal phenotypic variations in typical AD (tAD) and PCA. METHODS: Retinal phenotyping was carried out on ultra-widefield (UWF) images of 69 control, 24 tAD, and 25 PCA participants. RESULTS: Individuals with tAD (odds ratio [OR] = 2.76 [confidence interval (CI):1.24 to 6.10], P = .012) and PCA (OR = 3.40 [CI:1.25 to 9.22], P = .016) were more likely phenotyped as hard drusen. tAD (OR = 0.34 [CI:0.12 to 0.92], P = .035) were less likely to have soft drusen compared to control. Almost 3-fold increase in reticular pseudodrusen formation in tAD (OR = 2.93 [CI:1.10 to 7.76], P = .030) compared to control was estimated. DISCUSSION: Studying the peripheral retina may contribute to a better understanding of differences in retinal phenotypes of different AD variants.

Eye-tracking indices of impaired encoding of visual short-term memory in familial Alzheimer's disease.

The basis of visual short-term memory (VSTM) impairments in preclinical Alzheimer's disease (AD) remains unclear. Research suggests that eye movements may serve as indirect surrogates to investigate VSTM. Yet, investigations in preclinical populations are lacking. Fifty-two individuals from a familial Alzheimer's disease (FAD) cohort (9 symptomatic carriers, 17 presymptomatic carriers and 26 controls) completed the "Object-localisation" VSTM task while an eye-tracker recorded eye movements during the stimulus presentation. VSTM function and oculomotor performance were compared between groups and their association during encoding investigated. Compared to controls, symptomatic FAD carriers showed eye movement patterns suggestive of an ineffective encoding and presymptomatic FAD carriers within 6 years of their expected age at symptom onset, were more reliant on the stimuli fixation time to achieve accuracy in the localisation of the target. Consequently, for shorter fixation times on the stimuli, presymptomatic carriers were less accurate at localising the target than controls. By contrast, the only deficits detected on behavioural VSTM function was in symptomatic individuals. Our findings provide novel evidence that encoding processes may be vulnerable and weakened in presymptomatic FAD carriers, most prominently for spatial memory, suggesting a possible explanation for the subtle VSTM impairments observed in the preclinical stages of AD.

New insights into atypical Alzheimer's disease in the era of biomarkers.

Most patients with Alzheimer's disease present with amnestic problems; however, a substantial proportion, over-represented in young-onset cases, have atypical phenotypes including predominant visual, language, executive, behavioural, or motor dysfunction. In the past, these individuals often received a late diagnosis; however, availability of CSF and PET biomarkers of Alzheimer's disease pathologies and incorporation of atypical forms of Alzheimer's disease into new diagnostic criteria increasingly allows them to be more confidently diagnosed early in their illness. This early diagnosis in turn allows patients to be offered tailored information, appropriate care and support, and individualised treatment plans. These advances will provide improved access to clinical trials, which often exclude atypical phenotypes. Research into atypical Alzheimer's disease has revealed previously unrecognised neuropathological heterogeneity across the Alzheimer's disease spectrum. Neuroimaging, genetic, biomarker, and basic science studies are providing key insights into the factors that might drive selective vulnerability of differing brain networks, with potential mechanistic implications for understanding typical late-onset Alzheimer's disease.

Analyzing large Alzheimer's disease cognitive datasets: Considerations and challenges.

Recent data-sharing initiatives of clinical and preclinical Alzheimer's disease (AD) have led to a growing number of non-clinical researchers analyzing these datasets using modern data-driven computational methods. Cognitive tests are key components of such datasets, representing the principal clinical tool to establish phenotypes and monitor symptomatic progression. Despite the potential of computational analyses in complementing the clinical understanding of AD, the characteristics and multifactorial nature of cognitive tests are often unfamiliar to computational researchers and other non-specialist audiences. This perspective paper outlines core features, idiosyncrasies, and applications of cognitive test data. We report tests commonly featured in data-sharing initiatives, highlight key considerations in their selection and analysis, and provide suggestions to avoid risks of misinterpretation. Ultimately, the greater transparency of cognitive measures will maximize insights offered in AD, particularly regarding understanding the extent and basis of AD phenotypic heterogeneity.

Effects of lighting variability on locomotion in posterior cortical atrophy.

INTRODUCTION: Clinical reports describe patients with Alzheimer's disease (AD) exhibiting atypical adaptive walking responses to the visual environment; however, there is limited empirical investigation of such behaviors or factors modulating their expression. We aim to evaluate effects of lighting-based interventions and clinical presentation (visual- vs memory-led) on walking function in participants with posterior cortical atrophy (PCA) and typical AD (tAD). METHODS: Participants with PCA (n = 10), tAD (n = 9), and healthy controls (n = 12) walked to visible target destinations under different lighting conditions within two pilot repeated-measures design investigations (Experiment 1: 32 trials per participant; Experiment 2: 36 trials per participant). Participants walked to destinations with the floorpath interrupted by shadows varying in spatial extent (Experiment 1: no, medium, high shadow) or with different localized parts of the environment illuminated (Experiment 2: target, middle, or distractor illuminated). The primary study outcome for both experimental tasks was completion time; secondary kinematic outcomes were proportions of steps identified as outliers (Experiment 1) and walking path directness (Experiment 2). RESULTS: In Experiment 1, PCA participants overall demonstrated modest reductions in time taken to reach destinations when walking to destinations uninterrupted by shadows compared to high shadow conditions (7.1% reduction [95% confidence interval 2.5, 11.5; P = .003]). Experiment 2 found no evidence of differences in task performance for different localized lighting conditions in PCA participants overall. Neither experiment found evidence of differences in task performance between conditions in tAD or control participants overall. Completion time in both patient groups was longer relative to controls, and longer in PCA relative to tAD groups. DISCUSSION: Findings represent a quantitative characterization of a clinical phenomenon involving patients misperceiving shadows, implicating dementia-related cortico-visual impairments. Results contribute to evidence-based design guidelines for dementia-friendly environments.

Impairments of auditory scene analysis in posterior cortical atrophy.

Although posterior cortical atrophy is often regarded as the canonical 'visual dementia', auditory symptoms may also be salient in this disorder. Patients often report particular difficulty hearing in busy environments; however, the core cognitive process-parsing of the auditory environment ('auditory scene analysis')-has been poorly characterized. In this cross-sectional study, we used customized perceptual tasks to assess two generic cognitive operations underpinning auditory scene analysis-sound source segregation and sound event grouping-in a cohort of 21 patients with posterior cortical atrophy, referenced to 15 healthy age-matched individuals and 21 patients with typical Alzheimer's disease. After adjusting for peripheral hearing function and performance on control tasks assessing perceptual and executive response demands, patients with posterior cortical atrophy performed significantly worse on both auditory scene analysis tasks relative to healthy controls and patients with typical Alzheimer's disease (all P < 0.05). Our findings provide further evidence of central auditory dysfunction in posterior cortical atrophy, with implications for our pathophysiological understanding of Alzheimer syndromes as well as clinical diagnosis and management.

Augmenting Dementia Cognitive Assessment With Instruction-Less Eye-Tracking Tests.

Eye-tracking technology is an innovative tool that holds promise for enhancing dementia screening. In this work, we introduce a novel way of extracting salient features directly from the raw eye-tracking data of a mixed sample of dementia patients during a novel instruction-less cognitive test. Our approach is based on self-supervised representation learning where, by training initially a deep neural network to solve a pretext task using well-defined available labels (e.g. recognising distinct cognitive activities in healthy individuals), the network encodes high-level semantic information which is useful for solving other problems of interest (e.g. dementia classification). Inspired by previous work in explainable AI, we use the Layer-wise Relevance Propagation (LRP) technique to describe our network's decisions in differentiating between the distinct cognitive activities. The extent to which eye-tracking features of dementia patients deviate from healthy behaviour is then explored, followed by a comparison between self-supervised and handcrafted representations on discriminating between participants with and without dementia. Our findings not only reveal novel self-supervised learning features that are more sensitive than handcrafted features in detecting performance differences between participants with and without dementia across a variety of tasks, but also validate that instruction-less eye-tracking tests can detect oculomotor biomarkers of dementia-related cognitive dysfunction. This work highlights the contribution of self-supervised representation learning techniques in biomedical applications where the small number of patients, the non-homogenous presentations of the disease and the complexity of the setting can be a challenge using state-of-the-art feature extraction methods.

Sequences of cognitive decline in typical Alzheimer's disease and posterior cortical atrophy estimated using a novel event-based model of disease progression.

INTRODUCTION: This work aims to characterize the sequence in which cognitive deficits appear in two dementia syndromes. METHODS: Event-based modeling estimated fine-grained sequences of cognitive decline in clinically-diagnosed posterior cortical atrophy (PCA) ( n=94 ) and typical Alzheimer's disease (tAD) ( n=61 ) at the UCL Dementia Research Centre. Our neuropsychological battery assessed memory, vision, arithmetic, and general cognition. We adapted the event-based model to handle highly non-Gaussian data such as cognitive test scores where ceiling/floor effects are common. RESULTS: Experiments revealed differences and similarities in the fine-grained ordering of cognitive decline in PCA (vision first) and tAD (memory first). Simulation experiments reveal that our new model equals or exceeds performance of the classic event-based model, especially for highly non-Gaussian data. DISCUSSION: Our model recovered realistic, phenotypical progression signatures that may be applied in dementia clinical trials for enrichment, and as a data-driven composite cognitive end-point.

ReadClear: An Assistive Reading Tool for People Living with Posterior Cortical Atrophy.

BACKGROUND: Progressive reading impairment is an early and debilitating symptom of posterior cortical atrophy (PCA) arising from the progressive deterioration of visual processing skills. OBJECTIVE: The goal of this study was to test the effectiveness of a purpose-built reading app (ReadClear) co-produced with people living with PCA and designed to reduce the reading difficulties experienced by this population (e.g., getting lost in the page and missing words when reading). METHODS: Twenty subjects with PCA were included in a cross-over design home-based study aimed at determining whether ReadClear could 1) enhance the subjective reading experience (reading pleasantness) and 2) improve reading accuracy (reducing the number of reading errors) compared with a sham condition (a standard e-reader). RESULTS: Reading using ReadClear provided a better subjective reading experience than sham (p = 0.018, d = 0.5) and significantly reduced the percentage of reading errors (p < 0.0001, r = 0.82), particularly errors due to omissions (p = 0.01, r = 0.50), repeated words (p = 0.002, r = 0.69), and regressions in the text (p = 0.003, r = 0.69). We found that different kinds of reading errors were related to specific neuropsychological profiles. CONCLUSION: ReadClear can assist reading in people living with PCA by reducing the number of reading errors and improving the subjective reading experience of users.

Unusual Pattern of Reading Errors in a Patient with Posterior Cortical Atrophy.

Posterior cortical atrophy (PCA) is a degenerative condition characterized by a progressive deterioration of visual processing. Dyslexia constitutes an early and frequent visual symptom of the disease and previous comprehensive investigations in series of individuals have extensively documented a characteristic abundance of visual errors as the most prevalent error category in this population. Here we describe the profile of a patient with PCA, C.P., who presents an unusual prevalence of phonological, instead of purely visual, errors in his reading, in the context of an otherwise classic PCA phenotype. In keeping with the well-known PCA profile, C.P. exhibited deficits at the pre-lexical level with elements of crowding and defective early visual processing impairments but additionally showed an unusually prominent disruption of phonological processing. We also argue that our patient may have a refractory access type deficit in reading given that accuracy doubled with the introduction of a five-second response-stimulus interval. To our knowledge, no previous case of a refractory deficit affecting word reading has been reported in PCA. Our examination builds on previous knowledge about reading behaviour in PCA and describes a singular example of the rich phenotypic heterogeneity within the syndrome.

Retinal thickness as potential biomarker in posterior cortical atrophy and typical Alzheimer's disease.

BACKGROUND: Retinal thickness can be measured non-invasively with optical coherence tomography (OCT) and may offer compelling potential as a biomarker for Alzheimer's disease (AD). Retinal thinning is hypothesized to be a result of retrograde atrophy and/or parallel neurodegenerative processes. Changes in the visual pathway are of particular interest in posterior cortical atrophy (PCA), the most common atypical AD phenotype predominantly affecting the parietal-occipital cortices. We therefore evaluated retinal thickness as non-invasive biomarker of neurodegeneration in well-characterized participants with posterior cortical atrophy (PCA) and typical Alzheimer's disease (tAD). METHODS: Retinal thickness measures were acquired from 48 patient participants (N = 25 PCA; N = 23 tAD) fulfilling consensus diagnostic criteria and 70 age-matched controls. Participants were recruited between 2014 and 2016. All participants underwent optical coherence tomography (OCT) imaging, including measurement of peripapillary retinal nerve fiber layer (pRNFL) thickness and total macular thickness (mRT). Participants did not show evidence of any significant ophthalmological conditions. Subgroup analyses were performed in participants with available MRI and CSF measures, providing evidence of neurodegeneration and underlying AD pathology respectively. RESULTS: There was no evidence of overall between-group differences in pRNFL thickness (mean PCA 98.7 ± 12.2; tAD 99.9 ± 8.7; controls 99.6 ± 10.0 µm, one-way analysis of variance (ANOVA) p = 0.92) or total mRT (mean PCA 266.9 ± 16.3; tAD 267.8 ± 13.6; controls 269.3 ± 13.6 µm, one-way ANOVA p = 0.75). Similarly, subgroup analysis with MRI biomarkers (PCA = 18, tAD = 17, controls = 31) showing neurodegeneration, and CSF biomarkers (PCA = 18, tAD = 14, controls = 13) supporting underlying AD pathology did not provide evidence of overall between-group differences in pRNFL or mRT measures (all p > 0.3). CONCLUSIONS: Retinal thickness did not discriminate tAD and PCA from controls or from one another despite unequivocal differences on standard clinical, neuro-imaging and CSF measures. Findings from this well-characterized sample, including cases with PCA, do not support the hypothesis that retinal neurodegeneration, measured using conventional OCT, is a useful biomarker for AD or PCA.