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.

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.

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 (Cohen's 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 © 2016 John Wiley & Sons, Ltd.

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.

Burden, determinants, consequences and care of multimorbidity in rural and urbanising Telangana, India: protocol for a mixed-methods study within the APCAPS cohort.

INTRODUCTION: The epidemiological and demographic transitions are leading to a rising burden of multimorbidity (co-occurrence of two or more chronic conditions) worldwide. Evidence on the burden, determinants, consequences and care of multimorbidity in rural and urbanising India is limited, partly due to a lack of longitudinal and objectively measured data on chronic health conditions. We will conduct a mixed-methods study nested in the prospective Andhra Pradesh Children and Parents' Study (APCAPS) cohort to develop a data resource for understanding the epidemiology of multimorbidity in rural and urbanising India and developing interventions to improve the prevention and care of multimorbidity. METHODS AND ANALYSIS: We aim to recruit 2100 APCAPS cohort members aged 45+ who have clinical and lifestyle data collected during a previous cohort follow-up (2010-2012). We will screen for locally prevalent non-communicable, infectious and mental health conditions, alongside cognitive impairments, disabilities and frailty, using a combination of self-reported clinical diagnosis, symptom-based questionnaires, physical examinations and biochemical assays. We will conduct in-depth interviews with people with varying multimorbidity clusters, their informal carers and local healthcare providers. Deidentified data will be made available to external researchers. ETHICS AND DISSEMINATION: The study has received approval from the ethics committees of the National Institute of Nutrition and Indian Institute of Public Health Hyderabad, India and the London School of Hygiene and Tropical Medicine, UK. Meta-data and data collection instruments will be published on the APCAPS website alongside details of existing APCAPS data and the data access process (www.lshtm.ac.uk/research/centres-projects-groups/apcaps).

Evaluation of the Impact of the First Wave of COVID-19 and Associated Lockdown Restrictions on Persons with Disabilities in 14 States of India.

BACKGROUND: There is a paucity of data to assess the impact of the COVID-19 pandemic on persons with disabilities (PwDs) in India. About 27.4 million cases were reported as of 27 May 2021. The continuing pandemic in the form of subsequent waves is expected to have negative repercussions for the disabled globally, particularly in India, where access to health, rehabilitation, and social care services is very limited. Therefore, this study aimed to assess the impact of the COVID-19 pandemic and lockdown restrictions on PwDs in India. OBJECTIVE: To determine the level of disruption due to COVID-19 and the associated countrywide lockdown restrictions on PwD in India during the first wave. METHODS: Using a cross-sectional, mixed-methods approach, data were collected from a representative sample of 403 persons with disabilities in 14 states in India during the COVID-19 first wave at two different points in time (Lockdown and post-lockdown phase). Factors associated with the negative impact were examined using the Chi-square test for associations. The paired comparisons between 'lockdown' with the 'post-lockdown' phase are presented using McNemar's test and the marginal homogeneity test to compare the proportions. Additionally, a subsample of the participants in the survey was identified to participate in in-depth interviews and focus group discussions to gain in-depth insights on the study question and substantiate the quantitative findings. The framework approach was used to conduct a thematic analysis of the qualitative data. RESULTS: About 60% of the PwDs found it difficult to access emergency medical services during the lockdown, and 4.6% post lockdown (p < 0.001). Likewise, 12% found it difficult to access rehabilitation services during the lockdown, and 5% post lockdown (p = 0.03). About 76% of respondents were apprehensive of the risk of infection during the lockdown, and this increased to 92% post lockdown (p < 0.001). Parents with children were significantly impacted due to lockdown in the areas of Medical (p = 0.007), Rehabilitation (p = 0.001), and Mental health services (p = 0.001). The results from the qualitative study supported these quantitative findings. PWDs felt that the lockdown restrictions had negatively impacted their productivity, social participation, and overall engagement in everyday activities. Access to medicines and rehabilitation services was felt to be extremely difficult and detrimental to the therapeutic benefits that were gained by them during the pre-pandemic time. None of the pandemic mitigation plans and services was specific or inclusive of PWDs. CONCLUSIONS: COVID-19 and the associated lockdown restrictions have negatively impacted persons with disabilities during the first wave in India. It is critical to mainstream disability within the agenda for health and development with pragmatic, context-specific strategies and programs in the country.

Resting state functional connectivity abnormalities and delayed recall performance in patients with amnestic mild cognitive impairment.

Amnestic Mild Cognitive Impairment (aMCI) represents the transition between healthy aging and Alzheimer's dementia (AD) wherein gradual impairment of cognitive abilities, especially memory sets in. Impairment in episodic memory, especially delayed recall, is a hallmark of AD and therefore, patients with aMCI with more severe impairment in episodic memory are considered to be at greater risk of imminent conversion to AD. Brain structural and functional abnormalities were examined by comparing gray matter volumes, white matter micro-structural integrity and resting state functional connectivity (rsFC), between patients with aMCI (n = 46) having lower vs. higher episodic memory delayed recall (EM-DR) performance scores, correcting the influences of age, sex, number of years of formal education and total brain volumes using voxel-based morphometry, whole-brain tract based spatial statistics and dual regression analysis respectively. 'Low' performers (n = 27) when compared to 'high' performers (n = 19) showed significantly increased rsFC in the dorsal attention network (DAN) and central executive network (CEN) in the absence of demonstrable gray matter volumetric or white matter micro-structural integrity differences at family-wise error (FWE) corrected (p < 0.05) significance threshold. Follow-up data available for 38 (low performers = 22; high performers = 16) of the above 46 subjects (82.60% follow-up rate) over a median follow-up period of 24.5 months revealed that 7 subjects (18.42%) had converted to dementia. These converted subjects included 5 of the 22 low performers (22.72%) and 2 of the 16 high performers (12.5%) within the follow-up sample (n = 38). The results of the study indicate that imminent conversion of aMCI to dementia is higher in low performers in comparison to high performers, which may be characterized by increased rsFC in task positive networks, viz., DAN and CEN, as opposed to gray or white matter structural changes. This finding, therefore, might be considered as a prognostic indicator of progression from aMCI to dementia.

Differentiation of Early Alzheimer's Disease, Mild Cognitive Impairment, and Cognitively Healthy Elderly Samples Using Multimodal Neuroimaging Indices.

Brain resting-state functional connectivity (rsFC), white matter (WM) integrity, and cortical morphometry, as well as neuropsychological performance, have seldom been studied together to differentiate Alzheimer's disease (AD), mild cognitive impairment (MCI), and elderly cognitively healthy comparison (eCHC) samples in the context of the same study. We examined brain rsFC in samples of patients with mild AD (n = 50) and MCI (n = 49) in comparison with eCHC samples (n = 48) and then explored whether rsFC abnormalities can be linked to underlying gray matter (GM) volumetric and/or WM microstructural abnormalities. The mild AD sample showed significantly increased rsFC in the executive control network (ECN) and dorsal attention network (DAN) compared with the eCHC sample, and increased rsFC in ECN compared with MCI. Brain regions corresponding to both these resting-state networks (RSNs) showed significant reduction in fractional anisotropy in mild AD in comparison with eCHC. Significant GM volumetric reductions were observed in brain regions corresponding to both RSNs in the mild AD sample compared with MCI as well as eCHC samples. The association of default mode network-DAN anticorrelation with cognitive performances differentiated mild AD and MCI from eCHC sample. These findings highlight the association between brain structural and functional abnormalities as well as cognitive impairment that enables differentiation between early AD, MCI, and eCHC samples.

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 Petersen's 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.

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.

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 Alzheimer's dementia (AD) with comorbid diabetes mellitus (DM). Methods. The study included subjects with Alzheimer's dementia (AD) (n = 209), individuals with non-Alzheimer's 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.