Secondary language impairment in posterior cortical atrophy: insights from sentence repetition.

Introduction: Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by progressive impairment in visuospatial and perceptual function linked to atrophy of the occipito-parietal cortex. Besides the salient visual impairment, several studies have documented subtle changes in language may also be present. Sentence repetition is a highly constrained linguistic task involving multiple linguistic and cognitive processes and have been shown to be impaired in other AD spectrum disorders, with little consensus on its relevance in PCA. This aim of this study was to further delineate the linguistic and cognitive features of impaired language in PCA using a sentence repetition task. Method: Seven PCA patients and 16 healthy controls verbally repeated 16 sentences from the Boston Diagnostic Aphasia Examination. Responses were transcribed orthographically and coded for accuracy (percentage accuracy; percentage Correct Information Units; Levenshtein Distance) and for temporal characteristics (preparation duration (ms); utterance duration (ms); silent pause duration (ms); speech duration (ms); dysfluency duration (ms)). The potential modulating effects of attentional control and working memory capacity were explored. Results: PCA patients showed lower overall accuracy with retained semantic content of the sentences, and lower phonological accuracy. Temporal measures revealed longer preparation and utterance duration for PCA patients compared to controls, alongside longer speech duration but comparable dysfluency duration. PCA patients also showed comparable silent pause duration to controls. Attentional control, measured using the Hayling sentence completion task, predicted accuracy of sentence repetition. Discussion: The findings suggest that sentence repetition is impaired in PCA and is characterized by phonological, response planning and execution difficulties, underpinned in part by attentional control mechanisms. The emerging profile of language impairment in PCA suggests vulnerability of similar cognitive systems to other Alzheimer's syndromes, with subtle differences in clinical presentation.

Connected speech features in non-English speakers with Alzheimer's disease: protocol for scoping review.

BACKGROUND: A large body of literature indicates that connected speech profiles in patients with Alzheimer's disease (AD) can be utilized for diagnosis, disease monitoring, and for developing communication strategies for patients. Most connected speech research has been conducted in English, with little work in some European languages. Therefore, significant drawback remains with respect to the diversity of languages studied, and how the fragmentation of linguistic features differs across languages in AD. Accordingly, existing reviews on connected speech in AD have focused on findings from English-speaking patients; none have specifically focused on the linguistic diversity of AD populations. This scoping review is undertaken to provide the currently reported characteristics of connected speech in AD in languages other than English. It also seeks to identify the type of assessments, methods to elicit speech samples, type of analysis and linguistic frameworks used, and micro- and macro-linguistic features of speech reported in non-English speakers with AD. METHOD: We will conduct a scoping review of published studies that have quantitively assessed connected speech in AD in languages other than English. The inclusion criteria for the studies would be subject/s with a clinical diagnosis of AD. The search will include the electronic databases PubMed, Ovid-Embase, PsycINFO, Linguistic and Language Behaviour Abstracts (LLBA), and Web of Science up until March 2023. Findings will be mapped and described according to the languages studied, the methodology employed (e.g., patient characteristics, tasks used, linguistic analysis framework utilized), and connected speech profiles derived (e.g., micro- and macro-linguistic reported). DISCUSSION: The scoping review will provide an overview of languages studied in connected speech research in AD with variation in linguistic features across languages, thus allowing comparison with the established key features that distinguish AD patients from healthy controls. The findings will inform future research in connected speech in different languages to facilitate robust connected speech research in linguistically and ethnically diverse populations.

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.

Importance of Task Selection for Connected Speech Analysis in Patients with Alzheimer's Disease from an Ethnically Diverse Sample.

Features of linguistic impairment in Alzheimer's disease (AD) are primarily derived from English-speaking patients. Little is known regarding such deficits in linguistically diverse speakers with AD. We aimed to detail linguistic profiles (speech rate, dysfluencies, syntactic, lexical, morphological, semantics) from two connected speech tasks-Frog Story and picture description-in Bengali-speaking AD patients. The Frog Story detected group differences on all six linguistic levels, compared to only three with picture description. Critically, Frog Story captured the language-specific differences between the groups. Careful consideration should be given to the choice of connected speech tasks for dementia diagnosis in linguistically diverse populations.

Connected Speech Characteristics of Bengali Speakers With Alzheimer's Disease: Evidence for Language-Specific Diagnostic Markers.

Background and aim: Speech and language characteristics of connected speech provide a valuable tool for identifying, diagnosing and monitoring progression in Alzheimer's Disease (AD). Our knowledge of linguistic features of connected speech in AD is primarily derived from English speakers; very little is known regarding patterns of linguistic deficits in speakers of other languages, such as Bengali. Bengali is a highly inflected pro-drop language from the Indo-Aryan language family. It is the seventh most spoken language in the world, yet to date, no studies have investigated the profile of linguistic impairments in Bengali speakers with AD. The aim of this study was to characterize connected speech production and identify the linguistic features affected in Bengali speakers with AD. Methods: Participants were six Bengali speaking AD patients and eight matched controls from the urban metropolis, Kolkata, India. Narrative samples were elicited in Bengali using the Frog Story. Samples were analyzed using the Quantitative Production Analysis and the Correct Information Unit analyses to quantify six different aspects of speech production: speech rate, structural and syntactic measures, lexical measures, morphological and inflectional measures, semantic measures and measure of spontaneity and fluency disruptions. Results and conclusions: In line with the extant literature from English speakers, the Bengali AD participants demonstrated decreased speech rate, simplicity of sentence forms and structures, and reduced semantic content. Critically, differences with English speakers' literature emerged in the domains of Bengali specific linguistic features, such as the pro-drop nature of Bengali and its inflectional properties of nominal and verbal systems. Bengali AD participants produced fewer pronouns, which is in direct contrast with the overuse of pronouns by English AD participants. No obvious difficulty in producing nominal and verbal inflections was evident. However, differences in the type of noun inflections were evident; these were characterized by simpler inflectional features used by AD speakers. This study represents the first of its kind to characterize connected speech production in Bengali AD participants and is a significant step forward toward the development of language-specific clinical markers in AD. It also provides a framework for cross-linguistic comparisons across structurally distinct and under-explored languages.

Splenial white matter integrity is associated with memory impairments in posterior cortical atrophy.

Posterior cortical atrophy is an atypical form of Alzheimer's disease characterized by visuospatial impairments and predominant tissue loss in the posterior parieto-occipital and temporo-occipital cortex. Whilst episodic memory is traditionally thought to be relatively preserved in posterior cortical atrophy, recent work indicates that memory impairments form a common clinical symptom in the early stages of the disease. Neuroimaging studies suggest that memory dysfunction in posterior cortical atrophy may originate from atrophy and functional hypoconnectivity of parietal cortex. The structural connectivity patterns underpinning these memory impairments, however, have not been investigated. This line of inquiry is of particular interest, as changes in white matter tracts of posterior cortical atrophy patients have been shown to be more extensive than expected based on posterior atrophy of grey matter. In this cross-sectional diffusion tensor imaging MRI study, we examine the relationship between white matter microstructure and verbal episodic memory in posterior cortical atrophy. We assessed episodic memory performance in a group of posterior cortical atrophy patients (n = 14) and a group of matched healthy control participants (n = 19) using the Free and Cued Selective Reminding Test with Immediate Recall. Diffusion tensor imaging measures were obtained for 13 of the posterior cortical atrophy patients and a second control group of 18 healthy adults. Patients and healthy controls demonstrated similar memory encoding performance, indicating that learning of verbal information was preserved in posterior cortical atrophy. However, retrieval of verbal items was significantly impaired in the patient group compared with control participants. As expected, tract-based spatial statistics analyses showed widespread reductions of white matter integrity in posterior cortical regions of patients compared with healthy adults. Correlation analyses indicated that poor verbal retrieval in the patient group was specifically associated with microstructural damage of the splenium of the corpus callosum. Post-hoc tractography analyses in healthy controls demonstrated that this splenial region was connected to thalamic radiations and the retrolenticular part of the internal capsule. These results provide insight into the brain circuits that underlie memory impairments in posterior cortical atrophy. From a cognitive perspective, we propose that the association between splenial integrity and memory dysfunction could arise indirectly via disruption of attentional processes. We discuss implications for the clinical phenotype and development of therapeutic aids for cognitive impairment in posterior cortical atrophy.

Cortical diffusivity investigation in posterior cortical atrophy and typical Alzheimer's disease.

OBJECTIVES: To 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). METHODS: A 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. RESULTS: The 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). CONCLUSIONS: Diagnostic 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.

Pronounced Impairment of Activities of Daily Living in Posterior Cortical Atrophy.

INTRODUCTION: The impact of several dementia syndromes on activities of daily living (ADLs) has been well documented, but no study has yet investigated functional ability in posterior cortical atrophy (PCA). The primarily visual nature of deficits in this condition is likely to have a pronounced impact on ADLs. OBJECTIVE: The aim of this study was to profile functional change in PCA and identify predictors of change. METHOD: Twenty-nine PCA patients and 25 patients with typical Alzheimer's disease (AD) and their caregivers were included in this cross-sectional study. ADLs were assessed using the Disability Assessment for Dementia (DAD), administered to caregivers, assessing basic ADLs (e.g., eating, dressing) and instrumental ADLs (e.g., managing finances, meal preparation). The predictive utility of cognitive domains (Addenbrooke's Cognitive Examination), behavioural impairment (Cambridge Behavioural Inventory-Revised) and demographic variables on ADL ability was also examined. RESULTS: PCA patients showed significantly reduced total ADL scores compared to AD patients (medium effect size, d = -0.7; p < 0.05), with significantly more impairment on basic ADLs (large effect size, d = -0.8; p < 0.05) but similar impairment on instrumental ADLs (medium effect size, d = -0.5; p > 0.05). A model combining patient mood, disinhibition, apathy, symptom duration, and memory and attention/orientation scores explained the variance of scores in functional decline (61.2%), but the key factor predicting ADL scores was attention/orientation (p = 0.048). CONCLUSION: This study shows the profound impact of PCA on ADLs and factors underpinning patients' disability. Attention/orientation deficits were found to correlate and contribute to variance in ADL scores. Future work to develop tailored interventions to manage ADL impairment in PCA should take these findings into account.

Using memories to support the self in Alzheimer's disease.

The impact of memory loss on the self in Alzheimer's disease (AD) is poorly understood. Previous research is mixed on whether episodic or semantic memories are most important for supporting identity. The present study examined autobiographical memories cued by self-images (e.g., I am a father) and non-self-related cues in 16 AD patients and 29 healthy older adults. The AD group generated fewer self-images and memories compared to controls, but demonstrated similar temporal organization of self-cued memories. In both groups, self-images were supported by semantic memories that were temporally clustered around times of identity-formation. These self-supporting memories are proposed to form a scaffold to support the self and may persist the longest in AD, as opposed to memories from early adulthood per se. In both AD and control groups, self-images cued more semantic memories than non-self-relevant cues, further suggesting that semantic autobiographical memories play a fundamental role in supporting the self. These findings demonstrate that the self remains largely intact in AD, in spite of severe episodic memory deficits and global cognitive decline. In later stages of the disease, these self-supporting memories could provide effective tools for reminiscence therapy.

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.

Hippocampal network abnormalities explain amnesia after VGKCC-Ab related autoimmune limbic encephalitis.

OBJECTIVE: Limbic encephalitis associated with antibodies to components of the voltage-gated potassium channel complex (VGKCC-Ab-LE) often leads to hippocampal atrophy and persistent memory impairment. Its long-term impact on regions beyond the hippocampus, and the relationship between brain damage and cognitive outcome, are poorly understood. We investigated the nature of structural and functional brain abnormalities following VGKCC-Ab-LE and its role in residual memory impairment. METHOD: A cross-sectional group study was conducted. Twenty-four VGKCC-Ab-LE patients (20 male, 4 female; mean (SD) age 63.86 (11.31) years) were recruited post-acutely along with age- and sex-matched healthy controls for neuropsychological assessment, structural MRI and resting-state functional MRI (rs-fMRI). Structural abnormalities were determined using volumetry and voxel-based morphometry; rs-fMRI data were analysed to investigate hippocampal functional connectivity (FC). Associations of memory performance with neuroimaging measures were examined. RESULTS: Patients showed selective memory impairment. Structural analyses revealed focal hippocampal atrophy within the medial temporal lobes, correlative atrophy in the mediodorsal thalamus, and additional volume reduction in the posteromedial cortex. There was no association between regional volumes and memory performance. Instead, patients demonstrated reduced posteromedial cortico-hippocampal and inter-hippocampal FC, which correlated with memory scores (r = 0.553; r = 0.582, respectively). The latter declined as a function of time since the acute illness (r = -0.531). CONCLUSION: VGKCC-Ab-LE results in persistent isolated memory impairment. Patients have hippocampal atrophy with further reduced mediodorsal thalamic and posteromedial cortical volumes. Crucially, reduced FC of remaining hippocampal tissue correlates more closely with memory function than does regional atrophy.

Attention network dysfunction underlies memory impairment in posterior cortical atrophy.

Accumulating evidence suggests that memory is impaired in posterior cortical atrophy (PCA), alongside the early and defining visual disorder. The posterior parietal cortex is a key region of pathology in PCA and memory impairment may be the result of dysfunction of parietally dependent network function rather than the medial temporal lobe dependent dysfunction that defines the storage deficits in typical Alzheimer's disease. We assessed episodic memory performance and network function in16 PCA patients and 19 healthy controls who underwent structural and resting-state functional MRI and neuropsychological testing. Memory was assessed using the Free and Cued Selective Reminding Test (FCSRT), a sensitive test of episodic memory storage and retrieval. We examined correlations between memory performance and functional connectivity in the dorsal attention (DAN) and default mode network (DMN). Immediate recall on the FCSRT was relatively preserved in PCA patients. Total recall performance was impaired in patients relative to healthy controls and performance benefitted from retrieval cues. In patients only, disrupted connectivity in the DAN, but not the DMN, was associated with total recall. Memory impairment may arise from disruption to the dorsal attention network, subserved by the dorsal posterior parietal cortex, a key region of pathology in PCA, rather than classic medial temporal lobe memory circuitry.We propose that functional dysconnectivity in attentional circuits underpins memory impairment in PCA.

Lateral parietal contributions to memory impairment in posterior cortical atrophy.

Objective: Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterised by progressive impairment in visuospatial and perceptual function. Recent findings show that memory functioning can also be compromised early in the course of disease. In this study, we investigated the neural basis of memory impairment in PCA, and hypothesised that correlations would be observed with parietal cortex rather than classic medial temporal memory structures. Methods: Eighteen PCA patients, 15 typical Alzheimer's disease (tAD) patients and 21 healthy controls underwent memory testing with the Rey Auditory Verbal Learning Test (RAVLT) word list and MRI. Voxel-based morphometry (VBM) was used to identify regions in the parietal and medial temporal lobes that correlated with memory performance. Results: Compared with controls, PCA patients were impaired at learning, immediate and delayed recall and recognition of the RAVLT. Learning rate and immediate recall was significantly better in PCA compared to tAD, whereas there was no difference in delayed recall. Recognition memory also was not statistically different between patient groups, but PCA patients made significantly more false positive errors than tAD patients. VBM analysis in the PCA patients revealed a significant correlation between total learning and grey matter density in the right supramarginal gyrus, right angular gyrus and left postcentral gyrus. The left post central gyrus also significantly correlated with immediate and delayed recall and with recognition memory. No correlations were detected in the medial temporal lobe. Conclusions: The findings provide novel evidence that early verbal memory impairment is frequently observed in PCA, and is associated with damage to lateral parietal structures. The results have implications for the diagnosis and management of PCA.

Association between precuneus volume and autobiographical memory impairment in posterior cortical atrophy: Beyond the visual syndrome.

Posterior cortical atrophy is a neurodegenerative syndrome characterised by progressive disruption of visual and perceptual processing, associated with atrophy in the parieto-occipital cortex. Current diagnostic criteria describe relative sparing of episodic memory function, but recent findings suggest that anterograde memory is often impaired. Whether these deficits extend to remote memory has not been addressed. A large body of evidence suggests that the recollection of an autobiographical event from the remote past coincides with the successful retrieval of visual images. We hypothesised that the profound visual processing deficits in posterior cortical atrophy would result in impaired autobiographical memory retrieval. Fourteen posterior cortical atrophy patients, eighteen typical Alzheimer's disease patients and twenty-eight healthy controls completed the Autobiographical Interview. Autobiographical memory in posterior cortical atrophy was characterised by a striking loss of internal, episodic detail relative to controls and to same extent as typical Alzheimer's disease patients, in conjunction with an increase in external details tangential to the memory described. The memory narratives of posterior cortical atrophy patients showed a specific reduction in spatiotemporal and perceptual detail. Voxel-based morphometry analysis revealed atrophy of the parieto-occipital cortices in posterior cortical atrophy but relatively spared hippocampi bilaterally, compared with characteristic atrophy of the medial temporal lobes in typical Alzheimer's disease. Analysis of brain regions showing posterior cortical atrophy-specific atrophy revealed a correlation between perceptual details in autobiographical memory and grey matter density in the right precuneus. This study demonstrates remote memory impairment in posterior cortical atrophy despite relatively preserved medial temporal lobe structures. The results demonstrate, for the first time, profound autobiographical memory impairment in PCA and suggest that this is driven by the well-recognised deficits in higher-order visual processing. The findings are discussed in the context of posterior parietal contributions to imagery and memory, and the clinical implications of autobiographical memory impairment for diagnostic and management protocols in posterior cortical atrophy.

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.

Diagnosing young onset dementia can be challenging.

Although the risk of developing dementia increases with age, onset can be as early as the third or fourth decade of life. Genetic influences play a more important role in younger than in older people with dementia, so young onset dementia may cluster in families. Diagnosing young onset dementia is challenging. The range of possible presenting features is broad, encompassing behavioural, cognitive, psychiatric and neurological domains, and symptoms are often subtle initially. Frequently the complaints are misattributed to stress or depression, and the patient is falsely reassured that they are too young to have dementia. The most common causes of young onset dementia are early onset forms of adult neurodegenerative conditions and alcohol. Vascular dementia is the second most common cause of young onset dementia after Alzheimer's disease. Conventional vascular risk factors may be absent and diagnosis relies on imaging evidence of cerebrovascular disease. Obtaining a detailed history remains the most important part of the workup and usually requires corroboration by a third party. Undertaking a basic neurological examination is also important. Those with suspected young onset dementia should be referred to a neurology-led cognitive disorders clinic where available as the differenti diagnosis is considerably broader tha in older adults and requires specialist investigation.

Utility of testing for apraxia and associated features in dementia.

INTRODUCTION: Existing literature suggests that the presence or absence of apraxia and associated parietal deficits may be clinically relevant in differential diagnosis of dementia syndromes. AIM: This study investigated the profile of these features in Alzheimer's disease (AD) and frontotemporal dementia (FTD) spectrum disorders, at first presentation. METHODS: Retrospective case note analysis was undertaken in 111 patients who presented to the Oxford Cognitive Disorders Clinic, Oxford, UK, including 29 amnestic AD, 12 posterior cortical atrophy (PCA), 12 logopenic primary progressive aphasia (lvPPA), 20 behavioural variant FTD (bvFTD), 7 non-fluent variant PPA (nfvPPA), 6 semantic variant PPA (svPPA) and 25 patients with subjective cognitive impairment (SCI). The clinical features of interest were: limb apraxia, apraxia of speech (AOS), and left parietal symptoms of dyslexia, dysgraphia, and dyscalculia. RESULTS: The prevalence of limb apraxia was highest in PCA, amnestic AD, lvPPA and nfvPPA. AOS was only observed in nfvPPA. Associated parietal features were more prevalent in AD spectrum than FTD spectrum disorders. Group comparisons between key differential diagnostic challenges showed that lvPPA and nfvPPA could be significantly differentiated on the presence of left parietal features and AOS, and amnestic AD could be differentiated from bvFTD, svPPA and SCI by limb apraxia. Regression analysis showed that limb apraxia could successfully differentiate between AD and FTLD spectrum disorders with 83% accuracy. DISCUSSION: Disease-specific profiles of limb apraxia and associated deficits can be observed. FTD and AD spectrum disorders can be difficult to differentiate due to overlapping cognitive symptoms, and measures of apraxia, in particular, appear to be a promising discriminator.

Memory Impairment at Initial Clinical Presentation in Posterior Cortical Atrophy.

Posterior cortical atrophy (PCA) is characterized by core visuospatial and visuoperceptual deficits, and predominant atrophy in the parieto-occipital cortex. The most common underlying pathology is Alzheimer's disease (AD). Existing diagnostic criteria suggest that episodic memory is relatively preserved. The aim of this study was to examine memory performance at initial clinical presentation in PCA, compared to early-onset AD patients (EOAD). 15 PCA patients and 32 EOAD patients, and 34 healthy controls were entered into the study. Patients were tested on the Addenbrooke's Cognitive Examination (ACE-R), consisting of subscales in memory and visuospatial skills. PCA and EOAD patients were significantly impaired compared to controls on the ACE total score (p < 0.001), visuospatial skills (p < 0.001), and memory (p < 0.001). Consistent with the salient diagnostic deficits, PCA patients were significantly more impaired on visuospatial skills compared to EOAD patients (p < 0.001). However, there was no significant difference between patient groups in memory. Further analysis of learning, recall, and recognition components of the memory subscale showed that EOAD and PCA patients were significantly impaired compared to controls on all three components (p < 0.001), however, there was no significant difference between EOAD and PCA patients. The results of this study show that memory is impaired in the majority of PCA patients at clinical presentation. The findings suggest that memory impairment must be considered in assessment and management of PCA. Further study into memory in PCA is warranted, since the ACE-R is a brief screening tool and is likely to underestimate the presence of memory impairment.

Visuoconstructional Impairment in Subtypes of Mild Cognitive Impairment.

Clock Drawing Test performance was examined alongside other neuropsychological tests in mild cognitive impairment (MCI). We tested the hypothesis that clock-drawing errors are related to executive impairment. The current research examined 86 patients with MCI for whom, in prior research, cluster analysis was used to sort patients into dysexecutive (dMCI, n = 22), amnestic (aMCI, n = 13), and multidomain (mMCI, n = 51) subtypes. First, principal components analysis (PCA) and linear regression examined relations between clock-drawing errors and neuropsychological test performance independent of MCI subtype. Second, between-group differences were assessed with analysis of variance (ANOVA) where MCI subgroups were compared to normal controls (NC). PCA yielded a 3-group solution. Contrary to expectations, clock-drawing errors loaded with lower performance on naming/lexical retrieval, rather than with executive tests. Regression analyses found increasing clock-drawing errors to command were associated with worse performance only on naming/lexical retrieval tests. ANOVAs revealed no differences in clock-drawing errors between dMCI versus mMCI or aMCI versus NCs. Both the dMCI and mMCI groups generated more clock-drawing errors than the aMCI and NC groups in the command condition. In MCI, language-related skills contribute to clock-drawing impairment.