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). 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

Risk factors for mortality of patients with ceftriaxone resistant E. coli bacteremia receiving carbapenem versus beta lactam/beta lactamase inhibitor therapy

Objective: Extended spectrum β-lactamases (ESBL) producing Enterobacteriaceae predominantly E. coli and K. pneumoniae bacteremia have limited treatment options and high mortality. The objective was to determine the risk factors for in-hospital mortality particularly treatment with carbapenem versus beta lactam/beta lactamase combination (BL/BLI) in patients with ceftriaxone resistant E. coli bacteremia. A retrospective cohort study was conducted at the Aga Khan University, Karachi, Pakistan. Adult patients with sepsis and monomicrobial ceftriaxone resistant E. coli bacteremia were enrolled. Factors associated with mortality in patients were determined using logistic regression analysis. Results: Mortality rate was 37% in those empirically treated with carbapenem compared to 20% treated with BL/BLI combination therapy (p-value: 0.012) and was 21% in those treated with a carbapenem compared to 13% in patients definitively treated with BL/BLI combination therapy (p-value: 0.152). In multivariable logistic regression analysis, only Pitt bacteremia score of ≥ four was significantly associated with mortality (OR: 7.7 CI 2.6-22.8) while a urinary source of bacteremia was protective (OR: 0.26 CI 0.11-0.58). In-hospital mortality in patients with Ceftriaxone resistant E. coli bacteremia did not differ in patients treated with either a carbapenem or BL/BLI combination. However, Pitt bacteremia score of ≥ 4 was strongly associated with mortality

Connected speech characteristics of Bengali speakers with Alzheimer’s Disease: evidence for language-specific diagnostic markers

Background & 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 & 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 towards 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

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.MethodWe 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).DiscussionThe 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

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

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

The Mini-Addenbrooke's Cognitive Examination: a new assessment tool for dementia.

BACKGROUND/AIMS: We developed and validated the Mini-Addenbrooke's Cognitive Examination (M-ACE) in dementia patients. Comparisons were also made with the Mini Mental State Examination (MMSE). METHOD: The M-ACE was developed using Mokken scaling analysis in 117 dementia patients [behavioural variant frontotemporal dementia (bvFTD), n = 25; primary progressive aphasia (PPA), n = 49; Alzheimer's disease (AD), n = 34; corticobasal syndrome (CBS), n = 9] and validated in an independent sample of 164 dementia patients (bvFTD, n = 23; PPA, n = 82; AD, n = 38; CBS, n = 21) and 78 controls, who also completed the MMSE. RESULTS: The M-ACE consists of 5 items with a maximum score of 30. Two cut-offs were identified: (1) ≤25/30 has both high sensitivity and specificity, and (2) ≤21/30 is almost certainly a score to have come from a dementia patient regardless of the clinical setting. The M-ACE is more sensitive than the MMSE and is less likely to have ceiling effects. CONCLUSION: The M-ACE is a brief and sensitive cognitive screening tool for dementia. Two cut-offs (25 or 21) are recommended.This work was supported by funding to Forefront, a collaborative research group dedicated to the study of frontotemporal dementia and motor neurone disease, by the National Health and Medical Research council (NHMRC) of Australia program grant (1037746) and the Australian Research Council (ARC) Centre of Excellence in Cognition and Its Disorders Memory Node (CE110001021). S.H. is supported by the Graham Linford Fellowship from the Motor Neurone Disease Research Institute of Australia. S.M. is supported by Alzheimer Scotland (PhD Studentship). F.L. is supported by an Australian Postgraduate Award (PhD Scholarship). K.D. is supported by NIHR Cambridge Biomedical Research Centre. S.A. is supported by the NIHR Biomedical Research Centre, Oxford. C.R.B. is supported by a Clinician Scientist Fellowship from the Medical Research Council (MR/K010395/1). J.B.R. is supported by the Wellcome Trust (088324), Medical Research Council, McDonnell Foundation and the NIHR (Cambridge Biomedical Research Centre and Biomedical Research Unit in Dementia). E.M. is supported by the NHMRC Early Career Fellowship (1016399) and Alzheimer Association USA. J.R.H. is supported by an ARC Federation Fellowship (FF0776229).This is the final version of the article. It first appeared from Karger via http://dx.doi.org/10.1159/00036604

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

Selenium and Salt Interactions in Black Gram (Vigna mungo L.): Ion Uptake, Antioxidant Defense System, and Photochemistry Efficiency

Salinity is a major abiotic stress which limits crop production, especially under rainfed conditions. Selenium (Se), as an important micronutrient, plays a vital role in mitigating detrimental effects of different abiotic stresses. The objective of this research was to examine the effect of Se fertilization on black gram (Vigna mungo) under salt stress. Our results showed that salt stress (100 mM NaCl) in leaves significantly induced oxidative damage and caused a decline in relative water content, chlorophyll (Chl), stomatal conductance (gs), photochemical efficiency (Fv/Fm), sucrose, and reducing sugars. A low dose of Se (1.5 ppm) significantly reduced hydrogen peroxide content, malondialdehyde formation, cell membrane damage, and also improved antioxidative enzyme activities, including superoxide dismutase, catalase, ascorbate peroxidase, glutathione reductase, and glutathione peroxidase under salt stress. Se-treated plants exhibited higher Chl, gs, Fv/Fm, sucrose, and reducing sugars than untreated plants in response to salt stress. In addition, Se application enhanced Se uptake and reduced Na+ uptake, but Cl remained unaffected. Our results indicated that a low dose of Se effectively alleviated salt damage via inhibition of Na+ uptake and enhanced antioxidant defense resulting in a significant decrease in oxidative damage, and maintained gaseous exchange and PS II function for sucrose and reducing sugars accumulation in black gram

Paclobutrazol Improves Sesame Yield by Increasing Dry Matter Accumulation and Reducing Seed Shattering Under Rainfed Conditions

Several biotic and abiotic stresses significantly decrease the biomass accumulation and seed yield of sesame crops under rainfed areas. However, plant growth regulators (such as Paclobutrazol) can improve the total dry matter and seed production of the sesame crop. The effects of the paclobutrazol application on dry matter accumulation and seed yield had not been studied before in sesame under rainfed conditions. Therefore, a two-year field study during 2018 and 2019 was conducted with key objectives to assess the impacts of paclobutrazol on leaf greenness, leaf area, total dry matter production and partitioning, seed shattering, and seed yield of sesame. Two sesame cultivars (TS-5 and TS-3) were treated with four paclobutrazol concentrations (P0 = Control, P1 = 100 mg L-1, P2 = 200 mg L-1, P3 = 300 mg L-1). The experiment was executed in RCBD-factorial design with three replications. Compared with P0, treatment P3 improved the leaf greenness of sesame by 17%, 38%, and 60% at 45, 85, and 125 days after sowing, respectively. However, P3 treatment decreased the leaf area of sesame by 14% and 20% at 45 and 85 days after sowing than P0, respectively. Compared with P0, treatment P3 increased the leaf area by 46% at 125 days after sowing. On average, treatment P3 also improved the total biomass production by 21% and partitioning in roots, stems, leaves, capsules, and seeds by 23%, 19%, 23%, 22%, and 40%, respectively, in the whole growing seasons as compared to P0. Moreover, under P3 treatment, sesame attained the highest seed yield and lowest seed shattering by 27% and 30%, respectively, compared to P0. This study indicated that by applying the paclobutrazol concentration at the rate of 300 mg L-1 in sesame, the leaf greenness, leaf areas, biomass accumulation, partitioning, seed yield, and shatter resistance could be improved. Thus, the optimum paclobutrazol level could enhance the dry matter accumulation and seed production capacity of sesame by decreasing shattering losses under rainfed conditions