Shilpa Sadanand

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.

Identifying elders with neuropsychiatric problems in a clinical setting

Objective: Multiple health problems among the elderly necessitate a comprehensive enquiry to detect problems early and also initiate treatment. We utilized available validated instruments to comprehensively identify older persons with neuro-psychiatric problems including dementia and comorbid medical ailments in the screening desk of the geriatric clinic. Materials and Methods: Individuals aged 60 years and above seeking outpatient care at NIMHANS during a 2-year period (October 2008-September 2010) participated. We used General Health Questionnaire (12-item), AD8, questions to identify psychoses and neurological problems and a checklist of common medical ailments. A probable clinical diagnosis was made at the end by medical personnel based on ICD-10. Results: A total of 5,260 individuals were screened and more than one-third (36.7%) were women. About 50% had psychological distress (≥2 on GHQ-12), 20.1% had probable cognitive impairment (≥2 on AD8) and about 17% had symptoms suggestive of psychoses (≥1 on Psychoses screener). More than 65% had either a neurological or neurosurgical problems (≥1 on Neurological screener) and headache was the commonest complaint. At probable diagnosis, more than 50% had a neurological problem and over 30% had psychiatric disorders. Of these the most common psychiatric illnesses were psychotic disorders (22.0%), mood disorders (21.4%) and dementia (14.4%). The most common medical comorbidity included hypertension (36.4%), visual impairment (31.8%) and joint pains (30.5%). Nearly 80% had one or more medical comorbidity in addition to psychiatric illness. The overall set of instruments took about 15-20 minutes. It systematically and comprehensively guided in evaluating the elderly for neuropsychiatric problems and hence was collated to constitute the Instruments for Comprehensive Evaluation of the Elderly (ICE-E). Conclusions: ICE-E was brief, easy to administer and improved decision making even by personnel from a non-medical background. The instrument aided in systematically detecting neuro-psychiatric problems among the elderly (including psychological distress and cognitive changes) and other medical comorbidities.

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.

Dementia and diabetes mellitus: association with apolipoprotein e4 polymorphism from a hospital in southern India.

Objective. To evaluate the association of Apolipoprotein E4 (ApoE4) in Alzheimers dementia (AD) with comorbid diabetes mellitus (DM). Methods. The study included subjects with Alzheimers dementia (AD) (n = 209), individuals with non-Alzheimers dementia (nAD) (n = 122), individuals with parental history of AD (f/hAD) (n = 70), and control individuals who had normal cognitive functions and no parental history of dementia (NC) (n = 193). Dementia was diagnosed using International Classification of Diseases-10 revision (ICD-10) criteria. DM was assessed on the basis of self-report and/or use of antidiabetic medications. ApoE genotyping was done using sequence-specific primer polymerase chain reaction. Results. ApoE4 allele frequencies were highest among AD with comorbid DM (0.35) followed by AD without DM (0.25), nAD with DM (0.13), nAD without comorbid DM (0.12), and NC (0.08). Frequency of ApoE4 in persons with f/hAD was 0.13. The association of AD with co-morbid DM in ApoE4 carriers was more in comparison to NC with DM (OR = 5.68, P = 0.04). Conclusion. There is a significant association between AD with co-morbid DM and ApoE4 genotype.

Identifying psychological distress in elderly seeking health care

BACKGROUND Psychological distress in the elderly with various illness conditions often goes unrecognized. Since psychological distress is treatable, it is important to recognize it at the earliest to enhance recovery. This is an interim analysis of screening data of the elderly seeking health care in a hospital in India, with a focus on the 12-item General Health Questionnaire (GHQ-12), a screening instrument for psychological distress and a rationale for a higher cutoff score in help seeking elderly. MATERIALS AND METHODS A retrospective analysis of screening data of psychological distress using GHQ-12 in the elderly seeking care for neuropsychiatric conditions was carried out. Traditionally, ≥2 is considered positive for distress by GHQ-12. Receiver Operating Characteristic (ROC) curve was used to define new cutoff points for psychological distress. RESULTS At ≥2, 2443 (50%) of the elderly screened were recognized to be psychologically distressed. Using an ROC and optimum sensitivity and specificity measures, a cutoff score of ≥4 was observed to detect 30% of the elderly who had diagnosable mental health disorders. Female sex, illiteracy, and multiple co-morbidities were the factors that were associated with higher cutoff scores on GHQ-12 proposed here and psychiatric morbidity thereof. CONCLUSION There is greater psychological distress among the elderly seeking health care. Hence, it is important to screen them and identify those at higher risk. Using a higher cutoff score with a standardized instrument like GHQ-12 indicated that it was statistically valid to identify those elderly with higher distress in a busy out-patient setting.

A Retrospective Study on Relation between Cognitive Performance and LobarPerfusions of Brain in Alzheimer's Dementia using Single Photon EmissionComputer Tomography

Background and objectives: Alzheimer’s disease (AD) is a chronic neurodegenerative condition that progressively affects all cognitive domains. Patients with AD have been documented to have perfusion deficits. We aim to study the perfusion of lobes and its role in cognition among patients with AD. Methodology: Clinical data including cognitive scores on Hindi Mental Status Examination (HMSE) of 16 right handed patients with AD visiting geriatric clinic were recorded. Single Photon Emission Computer Tomography (SPECT) was acquired with standard protocol. Region of interest was applied at each of the frontal, temporal, parietal, occipital, cerebellar lobes to measure the regional perfusion. Results: Patients with AD aged 73.5 ± 8.5 years (6 males) with mean HMSE scores 11.69 ± 5.4 formed the study group. Left temporal lobe perfusion scores emerged as significant (p=0.04) predictor of cognitive scores in patients with AD. We observed a significant difference in perfusion between individual lobes within right hemisphere (p=0.003) and left hemisphere (p=0.009). Conclusion: In this sample of patients with AD we were able to demonstrate the differential pattern of brain perfusion within the intra-hemispheric lobes, possibly due to differential rate of degeneration. We were able to demonstrate a possible association between the left temporal lobe perfusion and cognitive scores in patients with AD.

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