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result(s) for
"Prasun Chatterjee"
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Blood Circulatory Level of Seven Sirtuins in Alzheimer’s Disease: Potent Biomarker Based on Translational Research
by
Dey, Sharmistha
,
Pathak, Mona
,
Pradhan, Rashmita
in
Aged
,
Alzheimer Disease
,
Alzheimer's disease
2022
Alzheimer’s disease (AD) is an accelerating neurodegenerative disorder. Dysfunction of mitochondria and oxidative stress contributes to the pathogenesis of AD. Sirtuins play a role in this pathway and can be a potential marker to study neurodegenerative changes. This study evaluated serum levels of all seven sirtuin (SIRT1–SIRT7) proteins in three study groups: AD, mild cognitive impairment (MCI) and geriatric control (GC) by surface plasmon resonance (SPR) technique. Further, it was validated by the Western blot experiment. ROC analysis was performed to differentiate the study group based on the concentration of serum SIRT proteins. Out of seven sirtuins, serum SIRT1, SIRT3 and SIRT6 levels (mean ± SD) were significantly decreased in AD (1.65 ± 0.56, 3.15 ± 0.28, 3.36 ± 0.32 ng/µl), compared to MCI (2.17 ± 0.39, 3.60 ± 0.51, 3.73 ± 0.48 ng/µl) and GC (2.84 ± 0.47, 4.55 ± 0.48, 4.65 ± 0.55 ng/µl). ROC analysis showed the cut-off value with high sensitivity and specificity for cognitive impairment (AD and MCI). The concentration declined significantly with the disease progression. No specific difference was observed in the case of other SIRTs between the study groups. This study reveals an inverse relation of serum SIRT1, SIRT3 and SIRT6 concentration with AD. ROC analysis showed that these serum proteins have greater accuracy in diagnosing of AD. This is the first report of estimation of all seven serum sirtuins and the clinical relevance of SIRT3 and SIRT6 as serum protein markers for AD.
Journal Article
Effect of Multimodal Intervention (computer based cognitive training, diet and exercise) in comparison to health awareness among older adults with Subjective Cognitive Impairment (MISCI-Trial)—A Pilot Randomized Control Trial
by
Khenduja, Preetika
,
Singh, Vishwajeet
,
Kumar, Deepa Anil
in
Adults
,
Biology and Life Sciences
,
Cognitive ability
2022
Introduction This study was aimed to investigate the effect of multimodal intervention on the cognitive functions of older adults with subjective cognitive impairment (SCI). Materials and methods Sixty subjects were randomized 1:1:1:1 to receive either computer based cognitive therapy (CBCT) or CBCT+Mediterranean equivalent diet (MED) or CBCT+MED+ Exercise regime and the control group. The intervention group received supervised CBCT twice a week to have 40 sessions, each of 40 minutes duration, and/ or supervised aerobic and resistive exercise twice a week for 24 weeks and or MED at home under the supervision of a dietician. The control group was provided with health awareness instructions for brain stimulating activities such as sudoku, mental maths, and learning music and new skills. Results Cognitive functions which was the primary outcome measure were assessed using the Post Graduate Institute Memory Scale (PGI-MS), and Stroop Colour and Word Test at baseline and after 6 months intervention period. As assessed by the PGI-MS, there was significant improvement in domains such as mental balance, attention and concentration, delayed recall, immediate recall, verbal retention of dissimilar pairs, Visual retention, and total score both in the unimodal and multimodal intervention groups. However, the improvement was observed to be the highest in the multimodal intervention group as compared to unimodal group. All the participants completed the trial. Conclusion This pilot randomized control trial indicated that multimodal intervention could be an effective non-pharmacological intervention in individuals with SCI for improving their cognitive functions.
Journal Article
Circulating small extracellular vesicles in Alzheimer’s disease: a case–control study of neuro-inflammation and synaptic dysfunction
by
Singh, Rishabh
,
Kumar, Saroj
,
Inampudi, Krishna Kishore
in
Advertising executives
,
Aged
,
Aged, 80 and over
2024
Background
Alzheimer’s disease (AD) is a neurodegenerative disease characterized by Aβ plaques and neurofibrillary tangles. Chronic inflammation and synaptic dysfunction lead to disease progression and cognitive decline. Small extracellular vesicles (sEVs) are implicated in AD progression by facilitating the spread of pathological proteins and inflammatory cytokines. This study investigates synaptic dysfunction and neuroinflammation protein markers in plasma-derived sEVs (PsEVs), their association with Amyloid-β and tau pathologies, and their correlation with AD progression.
Methods
A total of 90 [AD = 35, mild cognitive impairment (MCI) = 25, and healthy age-matched controls (AMC) = 30] participants were recruited. PsEVs were isolated using a chemical precipitation method, and their morphology was characterized by transmission electron microscopy. Using nanoparticle tracking analysis, the size and concentration of PsEVs were determined. Antibody-based validation of PsEVs was done using CD63, CD81, TSG101, and L1CAM antibodies. Synaptic dysfunction and neuroinflammation were evaluated with synaptophysin, TNF-α, IL-1β, and GFAP antibodies. AD-specific markers, amyloid-β (1–42), and p-Tau were examined within PsEVs using Western blot and ELISA.
Results
Our findings reveal higher concentrations of PsEVs in AD and MCI compared to AMC (
p
< 0.0001). Amyloid-β (1–42) expression within PsEVs is significantly elevated in MCI and AD compared to AMC. We could also differentiate between the amyloid-β (1–42) expression in AD and MCI. Similarly, PsEVs-derived p-Tau exhibited elevated expression in MCI compared with AMC, which is further increased in AD. Synaptophysin exhibited downregulated expression in PsEVs from MCI to AD (
p
= 0.047) compared to AMC, whereas IL-1β, TNF-α, and GFAP showed increased expression in MCI and AD compared to AMC. The correlation between the neuropsychological tests and PsEVs-derived proteins (which included markers for synaptic integrity, neuroinflammation, and disease pathology) was also performed in our study. The increased number of PsEVs correlates with disease pathological markers, synaptic dysfunction, and neuroinflammation.
Conclusions
Elevated PsEVs, upregulated amyloid-β (1–42), and p-Tau expression show high diagnostic accuracy in AD. The downregulated synaptophysin expression and upregulated neuroinflammatory markers in AD and MCI patients suggest potential synaptic degeneration and neuroinflammation. These findings support the potential of PsEV-associated biomarkers for AD diagnosis and highlight synaptic dysfunction and neuroinflammation in disease progression.
Journal Article
Behavioural issues in late life may be the precursor of dementia- A cross sectional evidence from memory clinic of AIIMS, India
by
Thakral, Meenal
,
Dwivedi, S. N.
,
Rao, Abhijith Rajaram
in
Activities of daily living
,
Aged
,
Anxiety - epidemiology
2020
Mild Behavioural Impairment (MBI), an \"at risk\" state for incident cognitive declin, is characterized by late onset, sustained neuropsychiatric symptoms of any severity which cannot be accounted for by other formal medical and psychiatric nosology. There is no study related to MBI from India.
In this cross-sectional observational study 124 subjects 60 years and above were recruited between March 2017 to October 2018, from memory clinic of department of Geriatric medicine with memory or behavioural complains. Subjects with major neurocognitive impairment (CDR score of 1 or more), major depressive disorder, generalized anxiety disorder and impaired activities of daily living (ADL) were excluded. Subjects with Mild Cognitive impairment (MCI) (CDR- 0.5), and Subjective cognitive impairment (SCI) (CDR- 0) were included. Neuropsychiatric Inventory Questionnaire (NPI-Q) was used to identify the presence of NPS. The ISTAART-MBI (International Society of Advance Alzheimer's Research and Treatment-Alzheimer's Association) diagnostic criteria was used to diagnose MBI. All the participants underwent a geriatric assessment using standardised screening. The objectives of this study was to determine the frequency of mild behavioural impairment (MBI), and its domains, in MCI or SCI and its association with comorbidities and geriatric syndromes. The mean age of the participants was 69.21, 71.77% (89) were male and 28.23% (35) were female. 41.13% (51) of these individuals were diagnosed with MBI. The MBI and non MBI group differed significantly in marital status, cognitive status and MCI subtype. The proportion of domains involved are as follows: decreased motivation 60.78%(31), emotional dysregulation 54.90% (28), impulse dyscontrol 68.63% (35), social inappropriateness 21.57%(11), abnormal perception 2 (3.93%). Presence of multi-morbidity, and diabetes, were statistically significant between the groups.
This study presents the first clinic-based prevalence estimates of MBI from Asia. Findings indicate a relatively high prevalence of MBI in predementia clinical states, impulse dyscontrol was the most commonly involved MBI domain. Multimorbidity, diabetes, urinary incontinence were other determinants of MBI.
Journal Article
Effect of Multimodal Intervention (computer based cognitive training, diet and exercise) in comparison to health awareness among older adults with Subjective Cognitive Impairment (MISCI-Trial)—A Pilot Randomized Control Trial
2022
Introduction This study was aimed to investigate the effect of multimodal intervention on the cognitive functions of older adults with subjective cognitive impairment (SCI). Materials and methods Sixty subjects were randomized 1:1:1:1 to receive either computer based cognitive therapy (CBCT) or CBCT+Mediterranean equivalent diet (MED) or CBCT+MED+ Exercise regime and the control group. The intervention group received supervised CBCT twice a week to have 40 sessions, each of 40 minutes duration, and/ or supervised aerobic and resistive exercise twice a week for 24 weeks and or MED at home under the supervision of a dietician. The control group was provided with health awareness instructions for brain stimulating activities such as sudoku, mental maths, and learning music and new skills. Results Cognitive functions which was the primary outcome measure were assessed using the Post Graduate Institute Memory Scale (PGI-MS), and Stroop Colour and Word Test at baseline and after 6 months intervention period. As assessed by the PGI-MS, there was significant improvement in domains such as mental balance, attention and concentration, delayed recall, immediate recall, verbal retention of dissimilar pairs, Visual retention, and total score both in the unimodal and multimodal intervention groups. However, the improvement was observed to be the highest in the multimodal intervention group as compared to unimodal group. All the participants completed the trial. Conclusion This pilot randomized control trial indicated that multimodal intervention could be an effective non-pharmacological intervention in individuals with SCI for improving their cognitive functions.
Journal Article
Establishment of Clinical Construct of Intrinsic Capacity in Older Adults and Its Prediction of Functional Decline
by
Kumar, Pramod
,
Upadhyay, Ashish Dutta
,
Dey, Aparajit Ballav
in
Activities of daily living
,
Aged
,
cognition
2022
Background: The World Health Organization has conceptualised the health and healthcare of older adults around the concept of healthy ageing. Healthy ageing is defined as \"the process of developing and maintaining the functional ability that enables well-being in older age\". This functional ability is the sum of two key factors: intrinsic capacity and interacting environment. This concept of intrinsic capacity encompasses a wide spectrum of health characteristics including the physiological and psychological changes associated with the ageing process. In general, IC declines from a high and stable state to an impaired status as people age. Monitoring individuals for changes in intrinsic capacity in the context of their environment will provide a holistic method of tracking the functioning of older adults at both a population and individual level, providing an opportunity to address any reversible factors of decline. However, this would require a clear and objective conceptualisation of the concept of intrinsic capacity. Methodology: One hundred subjects were recruited via invitation by advertisement on the institute campus. Study participants underwent detailed physical examination and measurement of various physical and chemical biomarkers which were likely to represent intrinsic capacity as evidenced by the literature review. Outcomes measured were a decline in ADL, IADL, mortality and hospitalisation over a follow-up period of six months. Exploratory factor analysis (EFA) was done to obtain a clinical construct of the proposed entity of intrinsic capacity. Unpaired t-test and univariate logistic regression were used to check for the association between the composite score (IC) and its domains with the decline in ADL, IADL, mortality and hospitalisation. Results: One composite score (composite IC score) and eight subfactors emerged. The composite score and subfactor domains showed good construct validity. Composite intrinsic capacity score and subdomains of strength and cognition were significantly different among subjects with and without ADL and IADL decline. Univariate logistic regression showed that composite intrinsic capacity score was a predictor of decline in ADL and IADL even after adjusting for age, sex, comorbidity status and education level of the subject with an adjusted odds ratio of 0.99 and 0.98, respectively. Subdomains of strength and cognition also predicted a decline in ADL and IADL independently. Conclusion: The development of an objective construct of the concept of intrinsic capacity, using commonly measured clinical and biochemical parameters, is feasible and predictive of the subsequent functionality of an individual. Keywords: intrinsic capacity, functional ability, domains, cognition, dependence, hospitalisation and mortality
Journal Article
Gait Parameters Change can be an Early Marker of Cognitive Impairment
by
Subramanian, Manicka S.
,
Singh, Vishwajeet
,
Dey, Aparajit B.
in
Cognition & reasoning
,
Cognition disorders
,
Cognitive ability
2024
Background and Objective:
Gait impairment leads to increased dependence, morbidity, institutionalization, and mortality in older people. We intended to assess gait parameters with the continuum of cognitive impairment and observe variation with the severity of cognitive impairment.
Materials and Methods:
This cross-sectional, observational study was conducted at the memory clinic of a tertiary care center. One hundred and twelve subjects were recruited, and cognition was assessed by the Clinical Dementia Rating scale. Usual gait was assessed by a 6-m walk test, and the dynamic gait was assessed using Biodex Gait Trainer™. Apart from crude analysis, adjusted linear regression was used to find the association of spatiotemporal gait parameters with cognitive decline.
Results:
Subjects were divided into subjective cognitive decline (SCD; n = 38), mild cognitive impairment (MCI; n = 40), and major neurocognitive disorder (MNCD; n = 34) groups. History of falls (23.7% vs. 30.0% vs. 67.7%, P < 0.001) and impaired activities of daily living (ADLs) (5.3% vs. 15.0% vs. 100%, P < 0.001) were significantly higher with cognitive decline. Age- and gender-adjusted regression analysis revealed that usual gait speed (0.8 vs. 0.6 vs. 0.5, P < 0.001) (m/s), total time (3.9 vs. 2.9 vs. 2.6, P = 0.022) (min), total distance (65.6 vs. 55.8 vs. 46.6, P = 0.025) (m), step cycle time (0.6 vs. 0.8 vs. 0.8, P = 0.020) (cycles/s), and step lengths were significant.
Conclusion:
Gait speed and other parameters worsened with increasing cognitive impairment. Changes in gait parameters might be a useful marker of declining cognition, though a long-term follow-up study is required to establish this association. Early intervention could be beneficial in preserving autonomy in patients with cognitive impairment.
Journal Article
Adherence to COVID-19 protective behaviours in India from May to December 2020: evidence from a nationally representative longitudinal survey
2022
ObjectivesSince the onset of the COVID-19 pandemic, behavioural interventions to reduce disease transmission have been central to public health policy worldwide. Sustaining individual protective behaviour is especially important in low-income and middle-income settings, where health systems have fewer resources and access to vaccination is limited. This study seeks to assess time trends in COVID-19 protective behaviour in India.DesignNationally representative, panel-based, longitudinal study.SettingWe conducted a panel survey of Indian households to understand how the adoption of COVID-19 protective behaviours has changed over time. Our data span peaks and valleys of disease transmission over May–December 2020.ParticipantsRespondents included 3719 adults from 1766 Indian households enrolled in the Harmonised Diagnostic Assessment of Dementia for the Longitudinal Ageing Study in India.AnalysisWe used ordinary least squares regression analysis to quantify time trends in protective behaviours.ResultsWe find a 30.6 percentage point (95% CI (26.7 to 34.5); p<0.01) decline in protective behaviours related to social distancing over the observation period. Mask wearing and handwashing, in contrast, decreased by only 4.3 percentage points (95% CI (0.97 to 7.6); p<0.05) from a high base. Our conclusions are unchanged after adjusting for recorded COVID-19 caseload and nationwide COVID-19 containment policy; we also observe significant declines across socioeconomic strata spanning age, gender, education and urbanicity.ConclusionWe argue that these changes reflect, at least in part, ‘COVID-19 fatigue,’ where adherence to social distancing becomes more difficult over time irrespective of the surrounding disease environment.
Journal Article
Six-minute walk test and its predictability in outcome of COVID-19 patients
by
Mohan, Anant
,
Kumar, Vijay
,
Singh, Vishwajeet
in
Aging (Individuals)
,
Attrition (Research Studies)
,
COVID-19
2022
BACKGROUND:
The world is worsely hit by the COVID-19 pandemic resulting in increased morbidity and mortality. Increased mortality has been observed in older adults with multiple comorbidities. Six-minute walk distance (6MWD) at admission can help us to guide the requirement of oxygen during hospital stay that can be used to determine which patient can be managed at home.
MATERIALS AND METHODS:
This study was a prospective observational study conducted on COVID-19 patients admitted at AIIMS, New Delhi, from October to December 2020. Patients aged more than 60 years were included in the study and underwent 6-min walk tests. Polypharmacy and multimorbidity were also assessed along with dyspnea which was measured on BORG scale. P < 0.05 was considered statistically significant. Statistical software STATA (version 14.2) was used for all the analyses.
RESULTS:
The mean age of the study population was 68.76 (7.4). Oxygen saturation prior to the 6-MWT was normal and has significantly higher than the post test (P ≤ 0.001). 6MWD was significantly correlated with pre values of oxygen saturation. 6MWD was observed more in patients who did not require oxygen during hospital stay. Self-reported dyspnea, pulse rate, oxygen saturation, and systolic blood pressure were significantly associated with the patients who had an oxygen requirement during the hospital stay.
CONCLUSION:
Self-reported dyspnea after 6MWT was found to be associated with oxygen requirement during hospital stay. Patients who have covered more distance in 6-min walk test have less oxygen requirement during hospital stay hence can be managed at home. This will reduce the health-care burden and will help to tackle the outburst during the ongoing pandemic.
Journal Article
A rare case of late‐onset limb‐girdle muscular dystrophy: Calpainopathy
2022
Limb‐girdle muscular dystrophy is a genetic disorder usually presenting in younger age patients. This case report presents a case of late‐onset limb‐girdle muscular dystrophy type R1 (Calpainopathy) in a 65 year old patient.
Journal Article