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Resistance to androgen receptor (AR) targeting therapeutics in prostate cancer (PC) is a significant clinical problem. Mechanisms by which this is accomplished include AR amplification and expression of AR splice variants, demonstrating that AR remains a key therapeutic target in advanced disease. For the first time we show that IKBKE drives AR signalling in advanced PC. Significant inhibition of AR regulated gene expression was observed upon siRNA-mediated IKBKE depletion or pharmacological inhibition due to inhibited AR gene expression in multiple cell line models including a LNCaP derivative cell line resistant to the anti-androgen, enzalutamide (LNCaP-EnzR). Phenotypically, this resulted in significant inhibition of proliferation, migration and colony forming ability suggesting that targeting IKBKE could circumvent resistance to AR targeting therapies. Indeed, pharmacological inhibition in the CWR22Rv1 xenograft mouse model reduced tumour size and enhanced survival. Critically, this was validated in patient-derived explants where enzymatic inactivation of IKBKE reduced cell proliferation and AR expression. Mechanistically, we provide evidence that IKBKE regulates AR levels via Hippo pathway inhibition to reduce c-MYC levels at cis-regulatory elements within the AR gene. Thus, IKBKE is a therapeutic target in advanced PC suggesting repurposing of clinically tested IKBKE inhibitors could be beneficial to castrate resistant PC patients.
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Quinase I-kappa B/fisiologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Receptores Androgênicos/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Via de Sinalização Hippo , Humanos , Quinase I-kappa B/antagonistas & inibidores , Masculino , Camundongos Nus , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/patologia , Receptores Androgênicos/metabolismo , Transdução de Sinais , Fatores de Transcrição/metabolismo , Transcrição Gênica , Proteínas de Sinalização YAPRESUMO
BACKGROUND/AIMS: In a linguistically diverse country such as India, challenges remain with regard to diagnosis of early cognitive decline among the elderly, with no prior attempts made to simultaneously validate a comprehensive battery of tests across domains in multiple languages. This study aimed to determine the utility of the Indian Council of Medical Research-Neurocognitive Tool Box (ICMR-NCTB) in the diagnosis of mild cognitive impairment (MCI) and its vascular subtype (VaMCI) in 5 Indian languages. METHODS: Literate subjects from 5 centers across the country were recruited using a uniform process, and all subjects were classified based on clinical evaluations and a gold standard test protocol into normal cognition, MCI, and VaMCI. Following adaptation and harmonization of the ICMR-NCTB across 5 different Indian languages into a composite Z score, its test performance against standards, including sensitivity and specificity of the instrument as well as of its subcomponents in diagnosis of MCI, was evaluated in age and education unmatched and matched groups. RESULTS: Variability in sensitivity-specificity estimates was noted between languages when a total of 991 controls and 205 patients with MCI (157 MCI and 48 VaMCI) were compared due to a significant impact of age, education, and language. Data from a total of 506 controls, 144 patients with MCI, and 46 patients with VaMCI who were age- and education-matched were compared. Post hoc analysis after correction for multiple comparisons revealed better performance in controls relative to all-cause MCI. An optimum composite Z-score of -0.541 achieved a sensitivity of 81.1% and a specificity of 88.8% for diagnosis of all-cause MCI, with a high specificity for diagnosis of VaMCI. Using combinations of multiple-domain 2 test subcomponents retained a sensitivity and specificity of >80% for diagnosis of MCI. CONCLUSIONS: The ICMR-NCTB is a "first of its kind" approach at harmonizing neuropsychological tests across 5 Indian languages for the diagnosis of MCI due to vascular and other etiologies. Utilizing multiple-domain subcomponents also retains the validity of this instrument, making it a valuable tool in MCI research in multilingual settings.
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Disfunção Cognitiva , Diversidade Cultural , Demência Vascular , Idioma , Testes Neuropsicológicos/normas , Idoso , Cognição , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/psicologia , Demência Vascular/diagnóstico , Demência Vascular/epidemiologia , Escolaridade , Feminino , Humanos , Índia/epidemiologia , Masculino , Reprodutibilidade dos Testes , Projetos de Pesquisa , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: While the burden of dementia is increasing in low- and middle-income countries, there is a low rate of diagnosis and paucity of research in these regions. A major challenge to study dementia is the limited availability of standardised diagnostic tools for use in populations with linguistic and educational diversity. The objectives of the study were to develop a standardised and comprehensive neurocognitive test battery to diagnose dementia and mild cognitive impairment (MCI) due to varied etiologies, across different languages and educational levels in India, to facilitate research efforts in diverse settings. METHODS: A multidisciplinary expert group formed by Indian Council of Medical Research (ICMR) collaborated towards adapting and validating a neurocognitive test battery, that is, the ICMR Neurocognitive Tool Box (ICMR-NCTB) in five Indian languages (Hindi, Bengali, Telugu, Kannada, and Malayalam), for illiterates and literates, to standardise diagnosis of dementia and MCI in India. RESULTS: Following a review of existing international and national efforts at standardising dementia diagnosis, the ICMR-NCTB was developed and adapted to the Indian setting of sociolinguistic diversity. The battery consisted of tests of cognition, behaviour, and functional activities. A uniform protocol for diagnosis of normal cognition, MCI, and dementia due to neurodegenerative diseases and stroke was followed in six centres. A systematic plan for validating the ICMR-NCTB and establishing cut-off values in a diverse multicentric cohort was developed. CONCLUSIONS: A key outcome was the development of a comprehensive diagnostic tool for diagnosis of dementia and MCI due to varied etiologies, in the diverse socio-demographic setting of India.
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Disfunção Cognitiva/diagnóstico , Diversidade Cultural , Demência/diagnóstico , Testes Neuropsicológicos/normas , Guias de Prática Clínica como Assunto/normas , Psicometria/normas , Demência/etiologia , Humanos , Índia , Doenças Neurodegenerativas/complicações , Psicometria/instrumentação , Psicometria/métodos , Acidente Vascular Cerebral/complicações , TraduçãoRESUMO
BACKGROUND: Previous studies in western countries have shown that about 30%-50% of patients with frontotemporal lobar degeneration (FTLD) have a positive family history, whereas the few epidemiological studies on FTLD done in Asia reported much lower frequencies. It is not clear the reason why the frequencies of FTLD with positive family history were lower in Asia. Furthermore, these findings were not from studies focused on family history. Therefore, it is necessary to conduct further studies on the family history of FTLD in Asia. This international multi-center research aims to investigate the family histories in patients with FTLD and related neurodegenerative diseases such as progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and motor neuron diseases in a larger Asian cohort. METHODS: Participants were collected from five countries: India, Indonesia, Japan, Taiwan, and Philippines. All patients were diagnosed with behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SD), progressive non-fluent aphasia (PA), frontotemporal dementia with motor neuron disease (FTD/MND), PSP, and corticobasal degeneration (CBD) according to international consensus criteria. Family histories of FTLD and related neurodegenerative diseases were investigated in each patient. RESULTS: Ninety-one patients were included in this study. Forty-two patients were diagnosed to have bvFTD, two patients had FTD/MND, 22 had SD, 15 had PA, one had PA/CBS, five had CBS and four patients had PSP. Family history of any FTLD spectrum disorder was reported in 9.5% in bvFTD patients but in none of the SD or PA. CONCLUSION: In contrast to patients of the western countries, few Asian FTLD patients have positive family histories of dementia.
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Degeneração Lobar Frontotemporal , Linhagem , Ásia/epidemiologia , Sintomas Comportamentais/diagnóstico , Família , Saúde da Família/estatística & dados numéricos , Feminino , Degeneração Lobar Frontotemporal/diagnóstico , Degeneração Lobar Frontotemporal/epidemiologia , Degeneração Lobar Frontotemporal/etiologia , Degeneração Lobar Frontotemporal/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais/estatística & dados numéricosRESUMO
PURPOSE: Connected speech analysis has been effectively utilized for the diagnosis and disease monitoring of individuals with Alzheimer's disease (AD). Existing research has been conducted mostly in monolingual English speakers with a noticeable lack of evidence from bilinguals and non-English speakers, particularly in non-European languages. Using a case study approach, we characterized connected speech profiles of two Bengali-English bilingual speakers with AD to determine the universal features of language impairments in both languages, identify language-specific differences between the languages, and explore language impairment characteristics of the participants with AD in relation to their bilingual language experience. METHOD: Participants included two Bengali-English bilingual speakers with AD and a group of age-, gender-, education-, and language-matched neurologically healthy controls. Connected speech samples were collected in first language (L1; Bengali) and second language (L2; English) using a novel storytelling task (i.e., Frog, Where Are You?). These samples were analyzed using an augmented quantitative production analysis and correct information unit analyses for productivity, fluency, syntactic and morphosyntactic features, and lexical and semantic characteristics. RESULTS: Irrespective of the language, AD impacted speech productivity (speech rate and fluency) and semantic characteristics in both languages. Unique language-specific differences were noted on syntactic measures (reduced sentence length in Bengali), lexical distribution (fewer pronouns and absence of reduplication in Bengali), and inflectional properties (no difficulties with noun or verb inflections in Bengali). Among the two participants with AD, the individual who showed lower proficiency and usage in L2 (English) demonstrated reduced syntactic complexity and morphosyntactic richness in English. CONCLUSIONS: Evidence from these case studies suggests that language impairment features in AD are not universal across languages, particularly in comparison to impairments typically associated with language breakdowns in English. This study underscores the importance of establishing connected speech profiles in AD for non-English-speaking populations, especially for structurally different languages. This would in turn lead to the development of language-specific markers that can facilitate early detection of language deterioration and aid in improving diagnosis of AD in individuals belonging to underserved linguistically diverse populations. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25412458.
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Doença de Alzheimer , Transtornos do Desenvolvimento da Linguagem , Multilinguismo , Humanos , Fala , IdiomaRESUMO
Objectives: The clock drawing test (CDT) is a widely used cognitive screening test. However, CDT performance is affected by education. This study examined an alternative, the Papadum test, designed for people with low levels of education/literacy. The association between education and test performance, correlation between CDT and Papadum test, and diagnostic accuracy of both CDT and Papadum tests were examined. Method: 89 healthy literate adults and 59 literate adults (all Bengali speaking) with a diagnosis of mild-moderate dementia from hospitals in Kolkata, India undertook the CDT and the Papadum test. Results: Education had a significant association with the CDT but not with the Papadum test. Across the whole sample there was a significant correlation between CDT and Papadum, but not within separate groups of healthy controls and patients. Diagnostic accuracy for the Papadum test was similar to that for CDT. Conclusions: Results highlight the strong influence that education has on CDT performance indicating that it is not suitable for those with low levels of literacy. The Papadum test could provide a viable alternative as a screening tool to the CDT for use with people who are illiterate or have low levels of education. Further validation studies are required.
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Demência , Adulto , Humanos , Testes Neuropsicológicos , Escolaridade , Demência/diagnóstico , Demência/psicologia , AlfabetizaçãoRESUMO
OBJECTIVE: Much of the information about the ethical practice of clinical neuropsychology has focused on North America. Additionally, of the scholarly publications on the intersection of ethical issues and cultural diversity practices in neuropsychology, most have focused on North America. The extent to which practitioners in other parts of the world are aware of, and find useful, such information is largely unknown. Similarly, the extent to which North American neuropsychologists are familiar with ethical issues and challenges encountered around the world is unknown. The purpose of this article is to advance the discussion of ethical issues in clinical neuropsychology from an international diversity perspective. METHOD: The article presents, via a panel interview format, the thoughts and experiences of a small sample of neuropsychologists who represent all continents except North America (and Antarctica). RESULTS: Neuropsychologists across continents share an ethical commitment to providing services that are beneficial, and not harmful, to the recipients of the services. Professional competence is at the heart of such services. CONCLUSIONS: Through continued and expanded dialogue about ethical issues with neuropsychology colleagues around the world, the potential exists for improvement in the provision of effective and compassionate care in our own towns.
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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.
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Doença de Alzheimer , Transtornos da Linguagem , Doença de Alzheimer/diagnóstico , Humanos , Idioma , Linguística , Semântica , FalaRESUMO
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.
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The Brixton Spatial Anticipation Test is a well-established test of executive function that evaluates the capacity to abstract, follow, and switch rules. There has been remarkably little systematic analysis of Brixton test performance in the prototypical neurodegenerative disorder of the frontal lobes: behavioural variant frontotemporal dementia (bvFTD) or evaluation of the test's ability to distinguish frontal from temporal lobe degenerative disease. We carried out a quantitative and qualitative analysis of Brixton performance in 76 patients with bvFTD and 34 with semantic dementia (SD) associated with temporal lobe degeneration. The groups were matched for demographic variables and illness duration. The bvFTD group performed significantly more poorly (U = 348, p < .0001, r = .58), 53% of patients scoring in the poor-impaired range compared with 6% of SD patients. Whereas bvFTD patients showed problems in rule acquisition and switching, SD patients did not, despite their impaired conceptual knowledge. Error analysis revealed more frequent perseverative errors in bvFTD, particularly responses unconnected to the stimulus, as well as random responses. Stimulus-bound errors were rare. Within the bvFTD group, there was variation in performance profile, which could not be explained by demographic, neurological, or genetic factors. The findings demonstrate sensitivity and specificity of the Brixton test in identifying frontal lobe degenerative disease and highlight the clinical value of qualitative analysis of test performance. From a theoretical perspective, the findings provide evidence that semantic knowledge and the capacity to acquire rules are dissociable. Moreover, they exemplify the separable functional contributions to executive performance.
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Demência Frontotemporal , Doença de Pick , Função Executiva , Lobo Frontal/diagnóstico por imagem , Humanos , Testes Neuropsicológicos , SemânticaRESUMO
OBJECTIVE: In the background of a large population of bilinguals globally, the study aimed to develop standards of neuropsychological testing in the context of bilingualism. Because bilingualism is known to affect cognitive processes, bilinguals and monolinguals were compared on their performance on cognitive tests, to investigate the possibility of the need for separate normative data for the two groups. METHOD: A comprehensive neuropsychological test battery, standardized across five Indian languages: the Indian Council of Medical Research-Neuro Cognitive Tool Box (ICMR-NCTB) was administered to 530 participants (267 monolingual and 263 bilinguals matched for age and education). A systematic method of testing cognition in bilinguals was developed; to identify the appropriate language for testing, ensure language proficiency of examiner, and to interpret the bilingual responses. Additionally, the performance of bilinguals on the ICMR-NCTB was compared with monolinguals. RESULTS: Cognitive testing in the bilingual context was performed in the most proficient language of the participants, by examiners well versed with the language. Results from the language-based tests suggested that the frequent occurrence of borrowed- and language-mixed words required consideration while scoring. The reported bilingual effect on cognitive processes did not reflect as differences in the performance between bilinguals and monolinguals. CONCLUSIONS: Observations from the study provide robust recommendations for neuropsychological testing in the context of bilingualism. Results indicate that separate normative data may not be required for bilinguals and monolinguals. The study will be relevant and provide a reference framework to address similar issues in the large population of bilinguals in other societies.
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OBJECTIVE: To study the occurrence of utilisation behaviour (UB) in patients with frontotemporal dementia (FTD). MATERIALS AND METHODS: Twenty patients who fulfilled all core Consensus statement criteria for FTD were examined by a neurologist experienced in dementia and by a clinical neuropsychologist. All patients had imaging evidence of predominantly frontal or frontotemporal involvement. Behavioural data were obtained from care givers using a semistructured questionnaire. Questions related to UB were asked in detail. Further assessment for UB was done during the interview with the patient using common objects. Only frank and coherent UB was considered for the study. For comparison, 34 patients with probable Alzheimer's disease diagnosed by the NINCDS-ADRDA criteria were also similarly studied. RESULTS: 80 per cent of our patients with FTD but none with probable Alzheimer's disease exhibited UB. Fourteen out of the 16 patients with FTD who exhibited UB were less than 70 years old. Among patients with UB, 88% exhibited a wide range of 'incidental' UB. Objects of daily use tended to trigger UB most commonly. Utilisation behaviour tended to correspond to premorbid habits in at least 75% of our patients. CONCLUSION: Utilisation behaviour may be more common in FTD patients than is currently recognised. The presence of UB should be queried in every patient suspected to be suffering from FTD. A comprehensive questionnaire for UB such as that used here could be useful.
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Atividades Cotidianas , Demência Frontotemporal/fisiopatologia , Desempenho Psicomotor , Idoso , Doença de Alzheimer/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Aphasia is a common consequence of stroke. To optimize recovery, it becomes critical as there are early identification and treatment of language deficits. The rising burden of stroke aphasia and lack of screening tools in the Indian context necessitates the need for a screening tool. OBJECTIVE: We aimed to adapt and validate the Frenchay Aphasia Screening Test (FAST) to the Indian context in two widely spoken Indian languages, Telugu and Kannada, for the literate and illiterate population. METHODS: A systematic process of adaptation and culturally appropriate modifications of the original FAST were done in 116 healthy controls and 115 patients. The validity of the adapted test was established. RESULTS: The optimum cut-off values for detecting aphasia in our sample ranged from 25 to 25.5 (literate) and 13.5 to 15.5 (illiterate) with high sensitivity and specificity. There was also a significant correlation between aphasia scores for adapted FAST and the Western Aphasia Battery (WAB), establishing good convergent validity. DISCUSSION: Results of the adaptation and validation of two Indian versions of FAST, suggest that it is an easy-to-use screening measure for detecting stroke-related language disabilities. The psychometric properties of the Indian version of FAST met the standardised requirements for adaptation and validation. CONCLUSIONS: The Indian version of FAST was found to be a reliable and valid bedside screening tool for aphasia in stroke patients. We aim that this study will facilitate the use of the test across other Indian languages and a large clinical population in the future.
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This work concerns the investigation of executive functions in patients with focal brain lesion. In order to identify the underlying substrates for executive functions, 54 patients with focal cortical (n=30), subcortical (n=13) and cerebellar damage (n=10) (M=9; F=1) in the age range of 24-65 years with a minimum of Class V education have been investigated. The patients were admitted to the Department of Neuromedicine of Bangur Institute of Neurology, Calcutta. Each patient with focal lesion was matched with a healthy normal subject controlling for age and education. The socio-economic background was also taken into consideration. Controls were selected from the families of other patients admitted to the institution and also from individuals who volunteered to act as controls. Here too, rigid criteria have been followed to select the normals. Mini Mental State Examination (MMSE) and General Health Questionnaire (GHQ) were administered to screen out the neurological and psychiatric abnormalities in selection of normal control and Wisconsin Card Sorting Test (WCST) was administered to find out the executive function, in terms of set-shifting ability. Since standard anatomical groupings can obscure more specific brain-behavior relations, group-comparison design does not always allow determination of the effective lesion responsible for a particular deficit (Godefroy et al., 1998). The Classification and Regression Tree (CART) analysis has been used to determine the brain-behavior relationships. The result reveals that the frontal lobes are essential determinants of set-shifting capacity. However, for optimal execution of set-shifting function, the frontal lobes require participation of other cortical, subcortical and cerebellar regions. The result has been discussed in the light of the existing theories and research reports.
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Atenção/fisiologia , Lesões Encefálicas/fisiopatologia , Mapeamento Encefálico , Resolução de Problemas/fisiologia , Enquadramento Psicológico , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Testes Neuropsicológicos , Inquéritos e QuestionáriosRESUMO
Episodic memory recall processes in Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) can be similarly impaired, whereas recognition performance is more variable. A potential reason for this variability could be false-positive errors made on recognition trials and whether these errors are due to amnesia per se or a general over-endorsement of recognition items regardless of memory. The current study addressed this issue by analysing recognition performance on the Rey Auditory Verbal Learning Test (RAVLT) in 39 bvFTD, 77 AD and 61 control participants from two centers (India, Australia), as well as disinhibition assessed using the Hayling test. Whereas both AD and bvFTD patients were comparably impaired on delayed recall, bvFTD patients showed intact recognition performance in terms of the number of correct hits. However, both patient groups endorsed significantly more false-positives than controls, and bvFTD and AD patients scored equally poorly on a sensitivity index (correct hits-false-positives). Furthermore, measures of disinhibition were significantly associated with false positives in both groups, with a stronger relationship with false-positives in bvFTD. Voxel-based morphometry analyses revealed similar neural correlates of false positive endorsement across bvFTD and AD, with both patient groups showing involvement of prefrontal and Papez circuitry regions, such as medial temporal and thalamic regions, and a DTI analysis detected an emerging but non-significant trend between false positives and decreased fornix integrity in bvFTD only. These findings suggest that false-positive errors on recognition tests relate to similar mechanisms in bvFTD and AD, reflecting deficits in episodic memory processes and disinhibition. These findings highlight that current memory tests are not sufficient to accurately distinguish between bvFTD and AD patients.
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BACKGROUND: The International Consortium (FTDC) that revised the diagnostic criteria for behavioural variant frontotemporal dementia (bvFTD) did not have an Asian representation. Whether the revised criteria are equally useful in the early detection of Asian bvFTD patients therefore remains largely unexplored. Earlier studies have indicated differences in clinical manifestations in Indian and other Asian bvFTD patients when compared to western groups. There is an urgent need for clarification, given the projected exponential rise in dementia in these countries and the imminent clinical trials on bvFTD. OBJECTIVE: To assess how Indian bvFTD patients fulfil the FTDC criteria, hypothesizing that our patients might present differently early in the illness. METHOD: In a hospital-based retrospective observational study, we assessed 48 probable bvFTD patients, diagnosed according to the FTDC criteria, for the speed with which these criteria were fulfilled, the frequency of individual symptoms and their order of appearance during the illness. RESULTS: Most of our patients presented with moderate to severe dementia, in spite of having relatively short onset to diagnosis times. Patients on average took 1.4 years from onset to meet the FTDC criteria, with 90% of them presenting with four or more symptoms at diagnosis. Disinhibition was the commonest symptom and the first symptom in most patients. CONCLUSION: With most patients presenting with advanced and florid disease, the FTDC criteria have little additional impact in early identification of bvFTD in India. Modifying the criteria further could allow detection of Indian patients early enough for their inclusion in future clinical trials.
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Demência Frontotemporal/diagnóstico , Adulto , Idade de Início , Idoso , Humanos , Índia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos RetrospectivosRESUMO
Environmental dependency (ED) behaviours, such as imitation behaviour (IB) and incidental utilization behaviour (UB), are considered pathognomonic of a frontal lesion and can play a unique role in diagnosing behavioural variant frontotemporal dementia (bvFTD). However, with only few focused observations of ED behaviour reported in earlier studies, their roles in the diagnosis of bvFTD have so far remained supportive. In this observational study, conducted in the cognitive clinic of a tertiary-care hospital, we explored the hypotheses that a focused and systematic search could uncover more ED behaviours in patients with bvFTD, and that the presence of ED behaviours such as incidental UB and IB should allow us to cleanly differentiate bvFTD from AD. Forty-one bvFTD patients and 75 probable AD patients, all diagnosed using accepted criteria, were seen by a neurologist and a neuropsychologist. Information regarding ED behaviour was obtained from the caregiver's history, observations for spontaneous behaviour and induction of the behaviour in the clinic. All ED behaviours were significantly more frequent in bvFTD compared with AD. UB (78 %; 66 % incidental) and IB (59 %) occurred exclusively in bvFTD. Multi-pronged and focused clinical assessment contributed to the high frequency of ED behaviours. Nearly two-thirds of bvFTD patients, but none with AD, showed three or more ED behaviours. We concluded that ED behaviours are more common in bvFTD than is currently recognized. UB, IB or three ED behaviours, if present, could clearly differentiate bvFTD from AD. A focused search should consistently uncover ED behaviours in bvFTD patients.
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Demência Frontotemporal/diagnóstico , Demência Frontotemporal/epidemiologia , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia , Testes Neuropsicológicos , Meio Social , Idoso , Feminino , Demência Frontotemporal/psicologia , Humanos , Comportamento Imitativo/fisiologia , Masculino , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Inquéritos e QuestionáriosAssuntos
Degeneração Lobar Frontotemporal/epidemiologia , Degeneração Lobar Frontotemporal/genética , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas/genética , Distribuição por Idade , Proteína C9orf72 , Comorbidade , Feminino , Estudos de Associação Genética , Marcadores Genéticos/genética , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Mutação/genética , Prevalência , Reprodutibilidade dos Testes , Medição de Risco/métodos , Sensibilidade e Especificidade , Distribuição por SexoRESUMO
Dementia is a clinical syndrome characterised by acquired loss of cognitive and emotional abilities that interfere with activities of daily living. It is a disease of the older adults. The overall prevalence of dementia in developed countries has been reported to be between 5% and 10% after 60 or 65 years and older. India is the second largest populous country. The prevalence doubles with every five-year increase in age. Looking at some studies, it appears that the prevalence of dementia in India is lower as compared to developed countries and even from other developing countries. The probable reasons for lower prevalence in India are enumerated as: False negatives, low life expectancy, shorter survival and duration of disease, low age-specific incidence. Risk factors include greater age, female sex, less education, positive family history, Down's syndrome, stroke and its risk factors, head trauma with loss of conscionsness and thyroid diseases. Protective factors include higher education, APOE2 gene, intake of antioxidant substances, use of anti-inflammatory drugs, oestrogen supplements in women and also cigarette smoking (controversial). Alzheimer's disease has been found to be commonest cause of dementia. Patients of dementia require proper evaluation and management requires a multidisciplinary approach. The government and the social organisations should come forward and only a concerted effort of all people in every sphere of life will enable to tackle the new menace of this country.