Keshav J. Kumar

Cognitive endophenotypes in OCD: a study of unaffected siblings of probands with familial OCD.

BACKGROUND Impairments in executive functions and non-verbal memory are considered potential endophenotype markers of obsessive-compulsive disorder (OCD). For the neuropsychological deficits to be considered endophenotypes, they should be demonstrable in unaffected family members. AIM To compare the neuropsychological performance in unaffected siblings of probands with familial OCD with that of individually matched healthy controls. METHODS Twenty-five unaffected siblings of OCD probands with familial OCD, and 25 individually matched healthy controls were assessed with tests of attention, executive function, memory and intelligence. RESULTS Unaffected siblings showed significant deficits in tests of decision making and behavioural reversal i.e., the Iowa Gambling Task (IGT) and the Delayed Alternation Test (DAT) respectively, but performed adequately in other tests. CONCLUSIONS Our study suggests that the deficits in decision making and behavioural reversal could be potential endophenotypes in OCD. These deficits are consistent with the proposed neurobiological model of OCD involving the orbitofrontal cortex. Future studies could couple cognitive and imaging strategies to identify neurocognitive endophenotypes in homogenous samples of OCD.

Impairment of verbal learning and memory and executive function in unaffected siblings of probands with bipolar disorder

OBJECTIVES Impairments in executive function and memory have been reported in relatives of patients with bipolar disorder, suggesting that they could be potential endophenotypes for genetic studies, but the findings are inconsistent. In this study, neuropsychological performance in unaffected siblings of probands with family loading for bipolar disorder is compared to that of individually matched healthy controls. We hypothesized that performance on tests of executive functions and memory would be impaired in unaffected siblings of probands with bipolar disorder compared to matched healthy controls. METHODS We evaluated 30 unaffected siblings of probands with bipolar I disorder and 30 individually matched healthy controls using tests of attention, executive function, and memory. Unaffected siblings and healthy control subjects did not differ with respect to gender, age, and years of education. RESULTS Unaffected siblings performed poorly on the Tower of London test (TOL), the Reys auditory verbal learning test (RAVLT), and the Reys complex figure test. In the multivariate analysis, significance was noted for the TOL, total number of moves (p = 0.007) and the RAVLT total learning score (p = 0.001). CONCLUSIONS Our study suggests that the deficits in verbal learning and memory and executive functions (planning) could be potential endophenotypes in bipolar disorder. These deficits are consistent with the proposed neurobiological model of bipolar disorder involving the frontotemporal and subcortical circuits. Future studies could couple cognitive and imaging strategies and genomics to identify neurocognitive endophenotypes in bipolar disorder.

Neuropsychological performance in OCD: a study in medication-naïve patients.

BACKGROUND Obsessive-compulsive disorder (OCD) is associated with impairments in multiple neuropsychological domains but the findings are rather inconsistent across studies. One potential reason for poor replication is the confounding influence of medications. There is limited research on neuropsychological performance in medication-naïve, never treated OCD patients. METHODS In this study, we assessed 31 medication-naïve, never-treated, DSM-IV OCD patients free of comorbid major depression and 31 healthy controls individually matched for age, gender and years of education, with tests of attention, executive function, memory reasoning and visuo-spatial function. RESULTS Medication-naïve OCD patients did not significantly differ from healthy controls on most neuropsychological tests. Patients performed somewhat poorly only on the highest goal hierarchy of the Tower of London (TOL) test (p=0.001, effect size=0.68). CONCLUSIONS It is intriguing to find that symptomatic, drug-naïve OCD patients did not significantly differ from healthy controls on most neuropsychological tests. Our finding of medium effect size on TOL highest goal hierarchy test suggests that brain regions outside the affective orbitofrontal loop may also be perhaps involved in OCD. This finding however needs replication because of modest effect size. Future studies should focus on studying medication-naïve, co-morbidity-free patients and relatives using symptom dimensions for consistent and robust findings.

Association between cortical volume loss and cognitive impairments in essential tremor

Impairment of cognitive functions occurs in essential tremor (ET) although the mechanism is largely unknown. A possible association between cognitive performance and brain atrophy in ET patients was examined using neuropsychological tests and voxel‐based morphometry (VBM).

Neurocognitive predictors of social cognition in remitted schizophrenia

Knowledge of how specific neurocognition (NC) abilities predict social cognition (SC) in schizophrenia has potential to guide novel integrated cognitive-remediation therapies. The scope of studies conducted in this field is limited as they have not examined a comprehensive set of SC domains and they employ small sample sizes of heterogeneous patient groups. We studied a broad range of NC (sustained attention, processing speed, verbal/visual memory and visual processing/encoding, cognitive flexibility and planning) and SC [different levels of theory of mind (ToM)], attributional bias, emotion recognition and social perception] abilities in 170 remitted schizophrenia patients. Multivariate regression analyses revealed attention and planning as predictors of 1st order ToM. Memory encoding was the strongest predictor of 2nd order ToM. Faux-pas recognition, social perception and emotion recognition were influenced by a combination of cognitive flexibility and memory encoding abilities. Overall, NC predicted anywhere between ~4% and 40% of variance observed in specific SC sub-dimensions of attributional bias (4%), 1st order (19%) and 2nd order (12%) theory of mind, faux-pas recognition (28%), social perception (29%) and emotion recognition (39%). Individual SC abilities are predicted by distinctive as well as shared NC abilities. These findings have important implications for integrated cognitive remediation.

A study of structural and functional connectivity in early Alzheimer's disease using rest fMRI and diffusion tensor imaging.

Alzheimers disease (AD) is a progressive neurodegenerative condition where in early diagnosis and interventions are key policy priorities in dementia services and research. We studied the functional and structural connectivity in mild AD to determine the nature of connectivity changes that coexist with neurocognitive deficits in the early stages of AD.

Neuropsychological markers of mild cognitive impairment: A clinic based study from urban India.

Background: Mild cognitive impairment (MCI) is a transitional stage between normal aging and dementia. Persons with MCI are at higher risk to develop dementia. Identifying MCI from normal aging has become a priority area of research. Neuropsychological assessment could help to identify these high risk individuals. Objective: To examine clinical utility and diagnostic accuracy of neuropsychological measures in identifying MCI. Materials and Methods: This is a cross-sectional study of 42 participants (22 patients with MCI and 20 normal controls [NC]) between the age of 60 and 80 years. All participants were screened for dementia and later a detailed neuropsychological assessment was carried out. Results: Persons with MCI performed significantly poorer than NC on word list (immediate and delayed recall), story recall test, stick construction delayed recall, fluency and Go/No-Go test. Measures of episodic memory especially word list delayed recall had the highest discriminating power compared with measures of semantic memory and executive functioning. Conclusion: Word list learning with delayed recall component is a possible candidate for detecting MCI from normal aging.

A Multimodal Structural and Functional Neuroimaging Study of Amnestic Mild Cognitive Impairment.

Examination of brain structural and functional abnormalities in amnestic mild cognitive impairment (aMCI) has the potential to enhance our understanding of the initial pathophysiological changes in dementia. We examined gray matter volumes and white matter microstructural integrity, as well as resting state functional connectivity (rsFC) in patients with aMCI (N = 48) in comparison to elderly cognitively healthy comparison subjects (N = 48). Brain volumetric comparisons were carried out using voxel-based morphometric analysis of T1-weighted images using the FMRIB Software Library. White matter microstructural integrity was examined using whole-brain tract-based spatial statistics analysis of fractional anisotropy maps generated from diffusion tensor imaging data. Finally, rsFC differences between the samples were examined by Multivariate Exploratory Linear Optimised Decomposition into Independent Components of the resting state functional magnetic resonance imaging time series, followed by between-group comparisons of selected networks using dual regression analysis. Patients with aMCI showed significant gray matter volumetric reductions in bilateral parahippocampal gyri as well as multiple other brain regions including frontal, temporal, and parietal cortices. Additionally, reduced rsFC in the anterior subdivision of the default mode network (DMN) and increased rsFC in the executive network were noted in the absence of demonstrable impairment of white matter microstructural integrity. We conclude that the demonstrable neuroimaging findings in aMCI include significant gray matter volumetric reductions in the fronto-temporo-parietal structures as well as resting state functional connectivity disturbances in DMN and executive network. These findings differentiate aMCI from healthy aging and could constitute the earliest demonstrable neuroimaging findings of incipient dementia.

Age, education and gender effects on neuropsychological functions in healthy Indian older adults

It is essential to use culturally appropriate, sensitive and specific tests that reflect true cognitive performance. However, several factors including age, education and gender can influence neuropsychological test performance. Objective To examine the effects of age, education and gender on neuropsychological function in older adults using measures of global cognitive screening, attention, working memory, executive functions, memory, construction, language and parietal focal signs. Methods This is a cross sectional normative study of 180 community-dwelling normal older adults. All participants were screened with the Hindi Mental Status Examination (HMSE), Everyday Activities Scale for India (EASI), Edinburgh handedness inventory (EDI) and MINI Screen, and followed by a detailed neuropsychological assessment. Results Stepwise regression analysis revealed that education was associated with better performance on all the neuropsychological tests. Females performed significantly better on measures of memory. Further, most of the illiterate subjects, including low educated participants, refused to cooperate on measures of executive functioning. Conclusion Education was found to be the strongest determinant of neuropsychological test performance followed by age and gender. Our study demonstrates that Indian healthy normal older adults with low education perform poorly on measures of planning and working memory. Traditional measures of planning and working memory should be avoided or used cautiously in the presence of low education. There is an urgent need to develop tasks for measuring executive functions, especially in low educated Indian older adults.

Illiteracy and Cognition in Older Adults

The article “Cognitive dysfunction in normally aging urban older adults” by Tripathi and Tiwari (2011) which appeared in volume 33 (2)[1] is interesting and has raised important issues regarding cognitive assessment in the elderly population. In this study the sample comprised of 89 community-dwelling normal elderly and most of the subjects (68.5%) had education below primary school level. Further, their results indicated that normal elderly had dysfunction in the domains of orientation and concentration. However, the findings of the article raise several questions for further examination. Here we have provided our observations in brief.