Rakesh Balachandar

Memory and executive functions in persons with type 2 diabetes: a meta-analysis

Literature suggests that persons with type 2 diabetes mellitus (T2DM) are at risk for cognitive impairment, hence dementia. Common domains reported to be affected in those with T2DM are memory and executive functions. The extent of influence of T2DM on these domains has varied among studies. A systematic review and meta‐analysis was carried out to understand whether sub‐domains contributed to the variations observed in published research. We searched ‘PubMed’, ‘ScienceDirect’, ‘SciVerseHub’, ‘Psychinfo’, ‘Proquest’ ‘Ebsco’ and ‘J‐gate Plus’ databases for published studies on cognition and T2DM among persons aged 50 years and older. Memory, executive functions and processing speed domain and sub‐domain scores were extracted; effect sizes (Cohens d) were calculated and analysed. Eight hundred seventeen articles were found. After various levels of filtering, 15 articles met the inclusion criteria for quantitative analyses. The analyses indicated that in comparison to controls, persons with T2DM showed decrements in episodic memory (d = −0.51), logical memory (d = −0.24), sub‐domain of executive functions which included phonemic fluency (d = −0.35) and cognitive flexibility (d = 0.52), and speed of processing (d = −0.22). We found no difference in the sub‐domains of verbal short‐term memory and working memory. The meta‐analysis revealed a detrimental effect of T2DM on cognitive sub‐domains, namely, episodic memory and cognitive flexibility. There was a trend for the logical memory, phonemic fluency and processing speed to be affected. The analysis indicates that T2DM is a detrimental factor on certain cognitive sub‐domains, rendering the person vulnerable to subsequent dementia. Copyright

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.

Effect of propofol anesthesia on resting state brain functional connectivity in Indian population with chronic back pain

Objective: Functional magnetic resonance imaging (fMRI) studies in healthy volunteers have shown alterations in brain connectivity following anesthesia as compared to the awake state. It is not known if the anesthesia-induced changes in brain connectivity are different in a pathological state. This study aims to evaluate changes in the resting state functional connectivity in the brain, after propofol anesthesia, in patients with chronic back pain (CBP). Materials and Methods: Fourteen adults with CBP were included in this prospective study over 6 months. After excluding structural brain pathology, a resting state fMRI was performed in the awake state, and the sequences were repeated after propofol anesthesia. The primary outcome measure was change in resting state connectivity after propofol. Students t-test was performed between the pre and post-propofol sedation data of all patients with total brain volume as covariates of interest. A repeated measures analysis of variance was used to compare pre- and post-propofol changes in cardiorespiratory parameters. Results: There were 8 male and 6 female patients in the study, and the mean age of the study population was 46.9 ± 11.3 years. Propofol sedation resulted in an increased strength of functional connectivity between the posterior cingulate cortex (PCC) and thalamus in patients with CBP, whereas there was a generalized decrease in functional integration within the large scale brain networks. The changes in cardiorespiratory parameters before and after propofol administration were not statistically significant. Conclusion: Strengthening of functional connectivity was seen between PCC and thalamus with decrease in large scale brain networks following propofol anesthesia in patients with CBP. These changes are similar to those previously described in normal volunteers.

DEVELOPMENT AND VALIDATION OF A NOVEL DEMENTIA OF THE ALZHEIMER’S TYPE (DAT) SCORE BASED ON METABOLISM FDG-PET IMAGING

cingulate to left supramarginal gyrus (r1⁄4 0.956, p< 2.0 x 10; Fig. 2). This relationship was not impacted by age or grey matter volume. No regions related to attention or executive function reached significance. Conclusions: Prior to dementia onset, we find that increased rs-fMRI strength within the DMN is positively related to memory scores. Compared to controls, previous work has found widespread increases in brain synchrony in those with DS (Anderson et al. 2013), and our own work has found both increased and decreased synchrony within the DMN (Koenig et al. 2015; 2017). Future work will include additional participants and will compare rs-fMRI to biological measures related to dementia. This work was supported by Alzheimer’s Association. The authors acknowledge technical support by Siemens Medical Solutions.

Resting-State Functional Connectivity Changes Associated with Visuospatial Cognitive Deficits in Patients with Mild Alzheimer Disease

Background/Aims: Alzheimer disease (AD) is a neurodegenerative disorder characterized by progressive disconnection of various brain networks leading to neuropsychological impairment. Pathology in the visual association areas has been documented in presymptomatic AD and therefore we aimed at examining the relationship between brain connectivity and visuospatial (VS) cognitive deficits in early AD. Methods: Tests for VS working memory, episodic memory and construction were used to classify patients with AD (n = 48) as having severe VS deficits (n = 12, female = 4) or mild deficits (n = 11, female = 4). Resting-state functional magnetic resonance imaging and structural images were acquired as per the standard protocols. Between-group differences in resting-state functional connectivity (rsFC) were examined by dual regression analysis correcting for age, gender, and total brain volume. Results: Patients with AD having severe VS deficits exhibited significantly reduced rsFC in bilateral lingual gyri of the visual network compared to patients with mild VS deficits. Conclusion: Reduced rsFC in the visual network in patients with more severe VS deficits may be a functional neuroimaging biomarker reflecting hypoconnectivity of the brain with progressive VS deficits during early AD.

Clinical and neuropsychological profile of persons with mild cognitive impairment, a hospital based study from a lower and middle income country

Mild Cognitive impairment (MCI) is an important pre-dementia stage to be identified towards prevention. We screened a large number of older adults seeking help at hospital and community towards a diagnosis of MCI and this study describe their clinical and neuropsychological profile. Older adults aged 60 years & above seeking help at NIMHANS outpatient & community services were screened for early cognitive deficits. Persons were diagnosed to have MCI according to Petersens criteria, after detailed clinical and neuropsychological assessments. Age, gender and education matched healthy controls were recruited for comparison. A total of 7469 older adults were screened during the study period (July 2012-December 2014). Less than 1% (n=56) were diagnosed with MCI. Majority were males, from urban background with an average of 13 years of education. They presented mainly with memory disturbances, more than 75% (n=43) were found to have amnestic type of MCI (aMCI). Of the aMCI subjects, majority (80%) had deficits in more than one cognitive domain. They performed significantly worse (p<0.001) on tests of episodic memory, logical memory, attention and executive functions. Neuropsychiatric symptoms were prevalent in 55% of MCI group and influenced their cognitive scores. The findings suggest that persons with MCI perform worse not only on memory tasks but also on some of the attention and executive functions tasks. As observed in earlier studies, amnestic multiple-domain MCI was the most common type of MCI in this study population. Indigenous assessment tools were of significant value in distinguishing MCI from normal ageing.

GRAPH THEORETICAL ANALYSIS OF FUNCTIONAL CONNECTIVITY PERTURBATIONS IN MILD COGNITIVE IMPAIRMENT

Background: Human brain consists of large, sparse and complex networks characterized by efficient small-world properties which ensures the optimal balance of specialized processing (segregation) and efficient communication (integration) of information. Mild Cognitive Impairment (MCI) is a transition state between normal ageing and Alzheimer’s dementia (AD) where decline in various cognitive domains such as memory, attention, concentration, executive functions and calculation sets in. Examination of functional connectivity at rest during the pre-clinical stage (i.e. MCI) of dementia could throw light on how functional connectivity disturbances could underlie cognitive dysfunction in AD. Methods: Graph theory-based analysis was used to isolate the topological properties of the brain functional networks on the basis of a 200 X 200 graph, G(V,E) where G is a non-zero subset with vertices V1⁄4 fMRI signals from the brain regions and edges E1⁄4 intermodal correlation coefficients as a measure of functional connectivity between nodes. We report normalized clustering coefficients (g), normalized characteristic short path length (l) and smallworldness (s) in 44 MCI and 44 elderly cognitively healthy comparison (eCHC) subjects over network sparsity thresholds of 6 to 30% with an increment of 1% to estimate correlation matrices between 200 brain regions. These network connectivity measures were analysed using brain connectivity toolbox. Results:MCI group in comparison to eCHC group, revealed two main findings: (1) at overall topological level, altered small-worldness and (2) at a nodal topological level, altered nodal characteristics in certain cerebral and cerebellar structures. Using the normalized clustering coefficient (g) values, the brain regions that showed significant differences (p <0.05 FWE-corrected) in MCI group were the right middle frontal gyrus, left superior frontal gyrus, right superior temporal gyrus, right culmen and left tuber of vermis. Conclusions: Efficient small-world

Search for neuroimaging biomarkers of amnestic mild cognitive impairment: A multimodal structural and functional neuroimaging study

has better reproducibility at 1.5T than FreeSurfer at 3T (p1⁄40.008) by 43%. The atrophy rate at 3T for the N1⁄4111 subjects, with the interquartile range in brackets, was -0.1% (-2.8, 3.2) for FreeSurfer and -0.1% (-1.4, 1.7) for MAPS-HBSI. At 1.5T it was 0.3% (-2.3, 2.0) and 0.5% (-1.0, 2.0). The right hippocampi had similar results. Conclusions:The reproducibility of hippocampal atrophy rate measurements for MAPS-HBSI at 3T is about 87% better than FreeSurfer at 3T. FreeSurfer at 1.5T is about 43% more reproducible at 3T. The superior performance of MAPS-HBSI at both 3Tand 1.5T may be due toMAPS-HBSI use of partial volume voxel while FreeSurfer uses discrete voxels.