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.

Do quantified sleep architecture abnormalities underlie cognitive disturbances in amnestic mild cognitive impairment?

The study was designed to gauge association between occult sleep-related breathing disturbances and sleep architecture changes on cognitive trajectories in subjects with amnestic mild cognitive impairment (aMCI) relative to cognitively normal healthy controls, phenotyped by neuroimaging. Subjects with aMCI and normal cognition were prospectively recruited. Following standardized neuropsychological and sleep questionnaire assessment they underwent a single overnight polysomnography (PSG); multimodality MRI was used to ascertain age-corrected radiological differences between the 2 groups. The aMCI cohort was followed up longitudinally with serial cognitive assessments for the next 3 years. Thirty seven subjects with aMCI and 24 control subjects consented for evaluation. Although occult moderate to severe obstructive sleep apnea (OSA) was more prevalent in aMCI (43.6%) as opposed to controls (22.7%); higher median apnea-hypopnea index (AHI = 11.5) and total apnea-hypopnea time (26.6 min) were also noted in aMCI relative to controls (6.6 and 11.4 min respectively), the differences were not statistically significant. In the aMCI group, better sleep efficiency, longer duration of REM sleep correlated with higher associative learning, free-recall/recognition memory performance. Higher AHI had negative correlation with visual memory scores. However longitudinal cognitive trends in the aMCI group over 3 years reflected relative stability (only 5% progressed to AD) notwithstanding imaging differences from controls and appeared to be independent of sleep parameters. The study concluded that despite associations between sleep efficiency, REM sleep and sleep-related breathing variables with neuropsychological test-scores in aMCI, these appear to be comorbidities rather than causative factors for the degree of cognitive impairment or its longitudinal trajectory.

Multimodality Neuroimaging in Mild Cognitive Impairment: A Cross-sectional Comparison Study.

BACKGROUND AND PURPOSE: Mild cognitive impairment (MCI) is a focus of considerable research. The present study aimed to test the utility of a logistic regression-derived classifier, combining specific quantitative multimodal magnetic resonance imaging (MRI) data for the early objective phenotyping of MCI in the clinic, over structural MRI data. METHODS: Thirty-three participants with cognitively stable amnestic MCI; 15 MCI converters to early Alzheimer's disease (AD; diseased controls) and 20 healthy controls underwent high-resolution T1-weighted volumetric MRI, diffusion tensor imaging (DTI), and proton magnetic resonance spectroscopy (1H MR spectroscopy). The regional volumes were obtained from T1-weighted MRI. The fractional anisotropy and mean diffusivity maps were derived from DTI over multiple white matter regions. The 1H MRS voxels were placed over posterior cingulate gyri, and N-acetyl aspartate (NAA)/creatine (Cr), choline (Cho)/Cr, myoinositol (mI/Cr), and NAA/mI ratios were obtained. A multimodal classifier comprising MR volumetry, DTI, and MRS was prepared. A cutoff point was arrived based on receiver operator characteristics analysis. Results were considered significant, if P < 0.05. RESULTS: The most sensitive individual marker to discriminate MCI from controls was DTI (90.9%), with a specificity of 50%. For classifying MCI from AD, the best individual modality was DTI (72.7%), with a high specificity of 87.9%. The multimodal classifier approach for MCI control classification achieved an area under curve (AUC) (AUC = 0.89; P < 0.001), with 93.9% sensitivity and 70% specificity. The combined classifier for MCI-AD achieved a highest AUC (AUC = 0.93; P < 0.001), with 93% sensitivity and 85.6% specificity. CONCLUSIONS: The combined method of gray matter atrophy, white matter tract changes, and metabolite variation achieved a better performance at classifying MCI compared to the application of individual MRI biomarkers.

Structural correlates of mild cognitive impairment: A clinicovolumetric study.

CONTEXT:: Annually 10-12% of patients with mild cognitive impairment (MCI) are likely to progress to Alzheimer's Disease (AD). The morphometric profile in stable non-converters has not been adequately characterized. AIMS: To determine the structural differences between amnestic MCI and early AD using volumetric magnetic resonance imaging (MRI) and its correlation with neuropsychological test performances. SETTINGS AND DESIGN:: This was a hospital-based case-control study. MATERIALS AND METHODS:: Twenty-four patients classified as having "non-progressor" MCI, 13 as having an early AD, and 25 controls, and assessed using neuropsychological evaluation, and three-dimensional T1-weighted 1.5T magnetic resonance maging (MRI) were included in the study. We used both voxel-based morphometry and automated regional volumetry to assess the topographical patterns of volume loss. STATISTICAL ANALYSIS USED: Post-hoc analysis of variance was done for comparison between means, and partial correlation analysis was done for correlating volumetric and cognitive measures. RESULTS:: Consistently, significant atrophy of the superior temporal gyrus, left hippocampus, and mesial frontoparietal regions were identified in patients with MCI in comparison to controls. Increased atrophy in the limbic regions, temporal neocortex, and precuneus was identified in patients with early AD in comparison to patients with MCI. While differences in retention and recall scores between the groups were independent of age and volumetric variables, significant correlations were observed between the learning and recall scores and the volume of hippocampus in patients with MCI as well as temporal neocortex in patients with AD. Atrophy of the superior temporal gyrus and mesial neocortical regions represents the structural correlate of amnestic MCI parallel to the development of hippocampal atrophy. CONCLUSIONS:: Identification of the pattern of volumetric abnormalities in patients with amnestic MCI in addition to atrophy of the medial temporal lobes necessitates a close follow up to continuously assess these patients for their progression to early AD.

Validity of Montreal Cognitive Assessment in non-english speaking patients with Parkinson's disease.

BACKGROUND: The Montreal Cognitive Assessment is a brief and easy screening tool for accurately testing cognitive dysfunction in Parkinson's disease. We tested its validity for use in non-English (Malayalam) speaking patients with Parkinson's disease. MATERIALS AND METHODS: We developed a Malayalam (a south-Indian language) version of Montreal Cognitive Assessment and applied to 70 patients with Parkinson's disease and 60 age- and education-matched healthy controls. Metric properties were assessed, and the scores were compared with the performance in validated Malayalam versions of Mini Mental Status Examination and Addenbrooke's Cognitive Examination. RESULTS: The Montreal Cognitive Assessment-Malayalam showed good internal consistency and test-retest reliability and its scores correlated with Mini Mental Status Examination (patients: R = 0.70; P < 0.001; healthy controls: R = 0.26; P = 0.04) and Addenbrooke's Cognitive Examination (patients: R = 0.8; P < 0.001; healthy controls: R = 0.52; P < 0.001) scores. CONCLUSION: This study establishes the reliability of cross-cultural adaptation of Montreal Cognitive Assessment for assessing cognition in Malayalam-speaking Parkinson's disease patients for early screening and potential future interventions for cognitive dysfunction.

A pilot study on utility of Malayalam version of Addenbrooke's Cognitive Examination in detection of amnestic mild cognitive impairment: A critical insight into utility of learning and recall measures.

AIMS: This pilot study sought to determine whether the Malayalam adaptation of Addenbrooke's Cognitive Examination (M-ACE) can effectively identify patients with amnestic mild cognitive impairment (a-MCI) and the impact of measures of learning and free recall. MATERIALS AND METHODS: A cohort of 23 patients with a-MCI aged between 55-80 years diagnosed as per current criteria and 23 group matched cognitively normal healthy controls (CNHC) were studied. The measures of acquisition and delayed recall were the Rey Auditory Verbal Learning Test (RAVLT) and Wechsler Memory Scale (WMS)-III (verbal and visual subsets) and Delayed Matching-to-sample Test (DMS)-48. Test scores of M-ACE registration and recall scores were included. To examine the differences in test performances between the groups, we compared the number of subjects with test scores less than 1.5 standard deviation (SD) of the control scores. Comparisons between a-MCI and controls were drawn using Fisher's exact test and Mann-Whitney U tests. RESULTS: M-ACE registration component ascertained on a 24-point scale failed to demonstrate any differences between a-MCI and controls (P = 0.665) as opposed to recall judged on a cumulative 10-point scale (P = 0.001). Significant differences were noted in RAVLT list learning (P < 0.001) and list recall (P = 0.003), WMS-III paragraph learning (P <0.001) and recall (P = 0.007), visual learning (P = 0.004) and recall (P = 0.001). CONCLUSIONS: M-ACE recall scores are an effective screening tool to identify patients with suspected a-MCI. Both word list and paragraph learning and recall components have been found to be sensitive to concretely identify a-MCI and impairment on at least 2 tests should be considered in the diagnostic criteria of MCI rather than rely on a single screening battery.

A critical evaluation of the lateralizing significance of material-specific memory deficits in patients with mesial temporal lobe epilepsy with hippocampal sclerosis.

To critically assess the value of material-specific memory deficits in lateralizing temporal lobe dysfunction preoperatively, we compared the neuropsychological data of 50 consecutive patients with unilateral mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS; right: 31, left: 19) with those of 50 age- and education-matched healthy control subjects. On case-control comparison, both the subcohorts with left and right MTLE-HS performed poorly on intelligence tests, in addition to individual memory tests. However, comparison of the verbal and visual memory functions between subcohorts with right and left MTLE-HS revealed that learning trials and delayed word list recall were the only tests that hypothesized left temporal lobe dysfunction. We conclude that material-specific memory deficits are largely test driven, but there is a lateralizing role for task-specific deficits in left MTLE-HS. Although neuropsychological data help to define baseline neuropsychological impairment, caution should be exercised in interpreting the lateralizing value of material-specific memory deficits prior to surgery.