Illiterate Addenbrooke's Cognitive Examination-III in Three Indian Languages: An Adaptation and Validation Study.

BACKGROUND: Literacy is an important factor that predicts cognitive performance. Existing cognitive screening tools are validated only in educated populations and are not appropriate for older adults with little or no education leading to poor performance on these tests and eventually leading to misdiagnosis. This challenge for clinicians necessitates a screening tool suitable for illiterate or low-literate older individuals. OBJECTIVES: The objective was to adapt and validate Addenbrooke's Cognitive Examination-III (ACE-III) for screening general cognitive functions in illiterate and low-literate older populations in the Indian context in three languages. METHOD: The Indian illiterate ACE-III was systematically adapted by modifying the original items of the Indian literate ACE-III to assess the cognitive functions of illiterates and low-literates with the consensus of an expert panel of professionals working in the area of dementia and related disorders. A total of 180 illiterate or low-literate participants (84 healthy-controls, 50 with dementia, and 46 with mild cognitive impairment [MCI]) were recruited from three different centers speaking Bengali, Hindi, and Kannada to validate the adapted version. RESULTS: The optimal cut-off score for illiterate ACE-III to distinguish controls from dementia in all 3 languages was 75. The optimal cut-off scores in distinguishing between controls and MCI ranged from 79 to 82, with a sensitivity ranging from 93% to 99% and a specificity ranging from 72% to 99%. CONCLUSION: The test is found to have good psychometric properties and is a reliable cognitive screening tool for identifying dementia and MCI in older adults with low educational backgrounds in the Indian context.

MoCA in five Indian languages: A brief screening tool to diagnose dementia and MCI in a linguistically diverse setting.

INTRODUCTION AND OBJECTIVES: Early dementia diagnosis in low and middle-income countries (LMIC) is challenging due to limited availability of brief, culturally appropriate, and psychometrically validated tests. Montreal Cognitive Assessment (MoCA) is one of the most widely used cognitive screening tests in primary and secondary care globally. In the current study, we adapted and validated MoCA in five Indian languages (Hindi, Bengali, Telugu, Kannada, and Malayalam) and determined the optimal cut-off points that correspond to screening for clinical diagnosis of dementia and MCI. METHODS: A systematic process of adaptation and modifications of MoCA was fulfilled. A total of 446 participants: 214 controls, 102 dementia, and 130 MCI were recruited across six centers. RESULTS: Across five languages, the area under the curve for diagnosis of dementia varied from 0.89 to 0.98 and MCI varied from 0.73 to 0.96. The sensitivity, specificity and optimum cut-off scores were established separately for five Indian languages. CONCLUSIONS: The Indian adapted MoCA is standardized and validated in five Indian languages for early diagnosis of dementia and MCI in a linguistically and culturally diverse population.

Picture-naming test for a linguistically diverse population with cognitive impairment and dementia.

BACKGROUND: Picture-naming tests (PNTs) evaluate linguistic impairment in dementia due to semantic memory impairment, impaired lexical retrieval or perceptual deficits. They also assess the decline in naming impairment at various stages of dementia and mild cognitive impairment (MCI) that occurs due to progressive cognitive impairment. With the increasing numbers of people with dementia globally, it is necessary to have validated naming tests and norms that are culturally and linguistically appropriate. AIMS: In this cross-sectional study we harmonized a set of 30 images applicable to the Indian context across five languages and investigated the picture-naming performance in patients with MCI and dementia. METHODS & PROCEDURES: A multidisciplinary expert group formed by the Indian Council of Medical Research (ICMR) collaborated towards developing and adapting a picture naming test (PNT) known as the ICMR-PNT in five Indian languages: Hindi, Bengali, Telugu, Kannada and Malayalam. Based on cross-cultural adaptation guidelines and item-wise factor analysis and correlations established separately across five languages, the final version of the ICMR-PNT test was developed. A total of 368 controls, 123 dementia and 128 MCI patients were recruited for the study. Psychometric properties of the adapted version of the ICMR-PNT were examined, and sensitivity and specificity were examined. OUTCOMES & RESULTS: The ICMR-PNT scores in all languages combined were higher in controls compared with patients with dementia and MCI (F2, 615 = 139.85; p < 0.001). Furthermore, PNT scores for MCI was higher in comparison with patients with dementia in all languages combined (p < 0.001). The area under the curve across the five languages ranged from 0.81 to 1.00 for detecting dementia. There was a negative correlation between Clinical Dementia Rating (CDR) and ICMR-PNT scores and a positive correlation between Addenbrooke's Cognitive Examination-III (ACE-III) and ICMR-PNT scores in control and patient groups. CONCLUSIONS & IMPLICATIONS: The ICMR-PNT was developed by following cross-cultural adaptation guidelines and establishing correlations using item-wise factor analysis across five languages. This adapted PNT was found to be a reliable tool when assessing naming abilities effectively in mild to moderate dementia in a linguistically diverse context. WHAT THIS PAPER ADDS: What is already known on this subject Picture-naming evaluates language impairment linked to naming difficulties due to semantic memory, lexical retrieval or perceptual disturbances. As a result, picture naming tests (PNTs) play an important role in the diagnosis of dementia. In a heterogeneous population such as India, there is a need for a common PNT that can be used across the wide range of languages. What this study adds to existing knowledge PNTs such as the Boston Naming Test (BNT) were developed for the educated, mostly English-speaking, Western populations and are not appropriate for use in an Indian context. To overcome this challenge, a PNT was harmonized in five Indian languages (Hindi, Bengali, Telugu, Kannada and Malayalam) and we report the patterns of naming difficulty in patients with MCI and dementia. The ICMR-PNT demonstrated good diagnostic accuracy when distinguishing patients with mild to moderate dementia from cognitively normal individuals. What are the potential or actual clinical implications of this work? With the growing number of persons suffering from Alzheimer's disease and other forms of dementia around the world, its critical to have culturally and linguistically relevant naming tests and diagnosis. This validated ICMR-PNT can be used widely as a clinical tool to diagnose dementia and harmonize research efforts across diverse populations.

Evaluation of Vascular Cognitive Impairment Using the ICMR-Neuro Cognitive Tool Box (ICMR-NCTB) in a Stroke Cohort from India.

Background and Purpose: Vascular cognitive impairment (VCI) presents with a spectrum of cognitive impairment due to stroke and poses a huge socioeconomic burden especially in low middle-income countries. There is a critical need for early recognition and identification of VCI patients. Therefore, we developed and validated culturally appropriate neuropsychological instruments, the ICMR-Neuro Cognitive Tool-Box (ICMR-NCTB) and Montreal Cognitive Assessment (MoCA) to diagnose vascular MCI and dementia in the Indian context. Methods: A total of 181 participants: 59 normal cognition, 25 stroke with normal cognition, 46 vascular MCI (VaMCI) and 51 vascular dementia (VaD) were recruited for the study. The ICMR-NCTB and MoCA were administered to patients with VCI and major cognitive domains were evaluated. Results: The ICMR-NCTB was found to have good internal reliability in VaMCI and VaD. The sensitivity of the ICMR-NCTB to detect VaMCI and VaD ranged from 70.8% to 72.9% and 75.9% to 79.7%, respectively, and the specificity for VaMCI and VaD ranged from 84.8% to 86.1% and 82.5% to 85.2%, respectively. The MoCA had excellent sensitivity and specificity to detect VaMCI and VaD at ideal cut-off scores. Conclusion: The ICMR-NCTB is a valid neuropsychological toolbox that can be used for comprehensive cognitive assessment and diagnosis of VCI in India. In addition, the Indian version of MoCA is more adept as a screening instrument to detect VCI due to its high sensitivity. The ICMR-NCTB will aid in early detection and management of many patients, thereby reducing the burden of vascular MCI and dementia in India.

Effects of Meditation on Structural Changes of the Brain in Patients With Mild Cognitive Impairment or Alzheimer's Disease Dementia.

Previous cross-sectional studies reported positive effects of meditation on the brain areas related to attention and executive function in the healthy elderly population. Effects of long-term regular meditation in persons with mild cognitive impairment (MCI) and Alzheimer's disease dementia (AD) have rarely been studied. In this study, we explored changes in cortical thickness and gray matter volume in meditation-naïve persons with MCI or mild AD after long-term meditation intervention. MCI or mild AD patients underwent detailed clinical and neuropsychological assessment and were assigned into meditation or non-meditation groups. High resolution T1-weighted magnetic resonance images (MRI) were acquired at baseline and after 6 months. Longitudinal symmetrized percentage changes (SPC) in cortical thickness and gray matter volume were estimated. Left caudal middle frontal, left rostral middle frontal, left superior parietal, right lateral orbitofrontal, and right superior frontal cortices showed changes in both cortical thickness and gray matter volume; the left paracentral cortex showed changes in cortical thickness; the left lateral occipital, left superior frontal, left banks of the superior temporal sulcus (bankssts), and left medial orbitofrontal cortices showed changes in gray matter volume. All these areas exhibited significantly higher SPC values in meditators as compared to non-meditators. Conversely, the left lateral occipital, and right posterior cingulate cortices showed significantly lower SPC values for cortical thickness in the meditators. In hippocampal subfields analysis, we observed significantly higher SPC in gray matter volume of the left CA1, molecular layer HP, and CA3 with a trend for increased gray matter volume in most other areas. No significant changes were found for the hippocampal subfields in the right hemisphere. Analysis of the subcortical structures revealed significantly increased volume in the right thalamus in the meditation group. The results of the study point out that long-term meditation practice in persons with MCI or mild AD leads to salutary changes in cortical thickness and gray matter volumes. Most of these changes were observed in the brain areas related to executive control and memory that are prominently at risk in neurodegenerative diseases.

Validation of ICMR Neurocognitive Toolbox for Dementia in the Linguistically Diverse Context of India.

Objectives: The growing prevalence of dementia, especially in low- and middle-income countries (LMICs), has raised the need for a unified cognitive screening tool that can aid its early detection. The linguistically and educationally diverse population in India contributes to challenges in diagnosis. The present study aimed to assess the validity and diagnostic accuracy of the Indian Council of Medical Research-Neurocognitive Toolbox (ICMR-NCTB), a comprehensive neuropsychological test battery adapted in five languages, for the diagnosis of dementia. Methods: A multidisciplinary group of experts developed the ICMR-NCTB based on reviewing the existing tools and incorporation of culturally appropriate modifications. The finalized tests of the major cognitive domains of attention, executive functions, memory, language, and visuospatial skills were then adapted and translated into five Indian languages: Hindi, Bengali, Telugu, Kannada, and Malayalam. Three hundred fifty-four participants were recruited, including 222 controls and 132 dementia patients. The sensitivity and specificity of the adapted tests were established for the diagnosis of dementia. Results: A significant difference in the mean (median) performance scores between healthy controls and patients with dementia was observed on all tests of ICMR-NCTB. The area under the curve for majority of the tests included in the ICMR-NCTB ranged from 0.73 to 1.00, and the sensitivity and specificity of the ICMR-NCTB tests ranged from 70 to 100% and 70.7 to 100%, respectively, to identify dementia across all five languages. Conclusions: The ICMR-NCTB is a valid instrument to diagnose dementia across five Indian languages, with good diagnostic accuracy. The toolbox was effective in overcoming the challenge of linguistic diversity. The study has wide implications to address the problem of a high disease burden and low diagnostic rate of dementia in LMICs like India.

Identification of GBA mutations among neurodegenerative disease patients from eastern India.

INTRODUCTION: GBA mutations have been reported in PD, PDD and DLB - but not associated with cognitive impairment for example in PSP, AD or MSA. However, frequencies of GBA mutations are ethnicity dependent. The present study aims to identify commonly reported GBA mutations (mostly from Asia), among eastern Indian patients with neurodegenerative disorders. METHODS: The patient cohort consisting of 198 classical PD cases, 136 PD cases with cognitive impairment, 184 cases with Parkinson Plus syndrome, 46 AD and 241 unrelated controls, from eastern India. Subjects were analyzed for IVS2 + 1A > G, p.Arg120Trp, p.His255Gln, p.Arg257Gln, p.Glu326Lys, p.Asn370Ser, p.Asp409His, p.Leu444Pro, & RecNciI by PCR-RFLP techniques and confirmed by Sanger sequencing method. RESULTS: We have identified only p.Leu444Pro variant among nine cases; three PDD, one DLB, two PD, two PSP and one AD patients in heterozygous condition. The highest frequency for p.Leu444Pro variant was found among PDD subgroup (3.95 %, P = 0.0134). An overall significant overrepresentation of positive family history (P = 0.000049), impaired recent memory (P = 0.0123) was observed among p.Leu444Pro carriers. Further, subgroup analysis for PD, PD-MCI and PDD, revealed statistically significant higher frequency of early age at onset (P = 0.0455), positive family history (P = 0.0025), higher UPDRS III score (off state) (P = 0.006), advanced H&Y stage (P = 0.045) and anxious behaviour (P = 0.0124) among p.Leu444Pro positive patients. CONCLUSION: The p.Leu444Pro mutation of GBA was found in patients with PD, PDD, DLB, PSP and AD. An Overall higher frequency of positive family history and impaired recent memory are significantly associated with for p.Leu444Pro carriers from eastern India. Our study also ascertains contribution of p.Leu444Pro to an earlier onset of PD, PD-MCI and PDD, higher UPDRS III score (off state) against positive family history background. Furthermore, taking into consideration other Indian studies, we can conclude that p.Leu444Pro mutation plays a limited role in PD and other neurodegenerative disorders.

Bilingualism and Its Implications for Neuropsychological Evaluation.

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.

Language Breakdown in Primary Progressive Aphasias.

Dementias with predominant language involvement, called primary progressive aphasias provide us with unique insight into systematic breakdown of language in neurodegenerative diseases and the structures and networks involved. Clinical and neuroimaging models quite distinct from those seen in stroke aphasias have evolved. In this short overview, we will discuss the cognitive processes involved in expressive and receptive verbal communication and how these processes are affected in the different variants of primary progressive aphasia producing distinctive clinical patterns. We will also discuss the brain's language network and how different components of the network break down in each of the primary progressive aphasia variants.

A Screening Tool to Detect Stroke Aphasia: Adaptation of Frenchay Aphasia Screening Test (FAST) to the Indian Context.

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.

Validation of Indian Council of Medical Research Neurocognitive Tool Box in Diagnosis of Mild Cognitive Impairment in India: Lessons from a Harmonization Process in a Linguistically Diverse Society.

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.

Standardising Dementia Diagnosis Across Linguistic and Educational Diversity: Study Design of the Indian Council of Medical Research-Neurocognitive Tool Box (ICMR-NCTB).

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.

False Recognition in Behavioral Variant Frontotemporal Dementia and Alzheimer's Disease-Disinhibition or Amnesia?

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.

Family history of frontotemporal lobar degeneration in Asia--an international multi-center research.

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.

Using the revised diagnostic criteria for frontotemporal dementia in India: evidence of an advanced and florid disease.

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.

Environmental dependency behaviours in frontotemporal dementia: have we been underrating them?

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.

Quantification of quetiapine in human plasma by reverse phase high performance liquid chromatography.

The objective of the present investigation is to develop and validate a simple, economical and reliable high performance liquid chromatography method for the quantification of quetiapine (CAS 111974-72-2) in human plasma with a quantification limit sufficiently low to support pharmacokinetic studies. Imipramine hydrochloride (CAS 113-52-0) was used as internal standard. The validated method allows quantification of quetiapine in 15-1000 ng/mL. The method was shown to be precise (< 7% coefficient of variation, CV) and accurate (< or = 10% relative error, RE). The correlation coefficient for quetiapine was > 0.9970. The simplicity of the assay and rapid liquid-liquid extraction make it an attractive procedure in high-throughput bioanalysis of quetiapine.

Utilisation behaviour in frontotemporal dementia.

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.