Effect of apolipoprotein E ε4 and its modification by sociodemographic characteristics on cognitive measures in South Asians from LASI-DAD.

BACKGROUND: We investigated the effects of apolipoprotein E (APOE) ε4 and its interactions with sociodemographic characteristics on cognitive measures in South Asians from the Diagnostic Assessment of Dementia for the Longitudinal Aging Study of India (LASI-DAD). METHODS: Linear regression was used to assess the association between APOE ε4 and global- and domain-specific cognitive function in 2563 participants (mean age 69.6 ± 7.3 years; 53% female). Effect modification by age, sex, and education were explored using interaction terms and subgroup analyses. RESULTS: APOE ε4 was inversely associated with most cognitive measures (p < 0.05). This association was stronger with advancing age for the Hindi Mental State Examination (HMSE) score (ßε4×age = -0.44, p = 0.03), orientation (ßε4×age = -0.07, p = 0.01), and language/fluency (ßε4×age = -0.07, p = 0.01), as well as in females for memory (ßε4×male = 0.17, p = 0.02) and language/fluency (ßε4×male = 0.12, p = 0.03). DISCUSSION: APOE Îµ4 is associated with lower cognitive function in South Asians from India, with a more pronounced impact observed in females and older individuals. HIGHLIGHTS: APOE Îµ4 carriers had lower global and domain-specific cognitive performance. Females and older individuals may be more susceptible to ε4 effects. For most cognitive measures, there was no interaction between ε4 and education.

Trajectories and correlates of poor mental health in India over the course of the COVID-19 pandemic: a nationwide survey.

INTRODUCTION: The COVID-19 pandemic had large impacts on mental health; however, most existing evidence is focused on the initial lockdown period and high-income contexts. By assessing trajectories of mental health symptoms in India over 2 years, we aim to understand the effect of later time periods and pandemic characteristics on mental health in a lower-middle income context. METHODS: We used data from the Real-Time Insights of COVID-19 in India cohort study (N=3709). We used covariate-adjusted linear regression models with generalised estimating equations to assess associations between mental health (Patient Health Questionnaire (PHQ-4) score; range 0-12) and pandemic periods as well as pandemic characteristics (COVID-19 cases and deaths, government stringency, self-reported financial impact, COVID-19 infection in the household) and explored effect modification by age, gender and rural/urban residence. RESULTS: Mental health symptoms dropped immediately following the lockdown period but rose again during the delta and omicron waves. Associations between mental health and later pandemic stages were stronger for adults 45 years of age and older (p<0.001). PHQ-4 scores were significantly associated with all pandemic characteristics considered, including estimated COVID-19 deaths (PHQ-4 difference of 0.10 units; 95% CI 0.06 to 0.13), government stringency index (0.14 units; 95% CI 0.11 to 0.18), self-reported major financial impacts (1.20 units; 95% CI 1.09 to 1.32) and COVID-19 infection in the household (0.36 units; 95% CI 0.23 to 0.50). CONCLUSION: While the lockdown period and associated financial stress had the largest mental health impacts on Indian adults, the effects of the pandemic on mental health persisted over time, especially among middle-aged and older adults. Results highlight the importance of investments in mental health supports and services to address the consequences of cyclical waves of infections and disease burden due to COVID-19 or other emerging pandemics.

Polygenic Risk Scores for Alzheimer's Disease and General Cognitive Function Are Associated With Measures of Cognition in Older South Asians.

Genome-wide association studies (GWAS) conducted in European ancestry (EA) have identified hundreds of single-nucleotide polymorphisms (SNPs) associated with general cognitive function and/or Alzheimer's disease (AD). The association between these SNPs and cognitive function has not been fully evaluated in populations with complex genetic substructure such as South Asians. This study investigated whether SNPs identified in EA GWAS, either individually or as polygenic risk scores (PRSs), were associated with general cognitive function and 5 broad cognitive domains in 932 South Asians from the Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD). We found that SNPs identified from AD GWAS were more strongly associated with cognitive function in LASI-DAD than those from a GWAS of general cognitive function. PRSs for general cognitive function and AD explained up to 1.1% of the variability in LASI-DAD cognitive domain scores. Our study represents an important stepping stone toward better characterization of the genetic architecture of cognitive aging in the Indian/South Asian population and highlights the need for further research that may lead to the identification of new variants unique to this population.

Molecular characterization of Clostridioides difficile by multi-locus sequence typing (MLST): A study from tertiary care center in India.

OBJECTIVES: Clostridioides difficile is an important pathogen responsible for antibiotic-associated diarrhoea (AAD). This study was aimed to perform multi-locus sequence typing (MLST) of C. difficile isolates from AAD cases and to understand the clonal relationship between these C. difficile strains. METHODS: Thirty five strains and a standard strain C.difficile ATCC 9689 were characterized by polymerase chain reaction assay (PCR) for toxin genes (tcdA and tcdB gene) detection and MLST. RESULTS: MLST results revealed that the most common sequence types were ST-17, ST-54, ST-63. The cluster analysis revealed that strains isolated from AAD patients generated 12 MLST sequence types grouped into two distinct evolutionary lineages. CONCLUSIONS: ST 17 is most prominent sequence type. This is the first report of MLST based study of C. difficile from India. Further studies from diverse geographical regions can help better understand the epidemiology of CDI in India.

Lung cancer in the older population:Interactive effects of angiotensin converting enzyme gene polymorphism (rs 4340 ID) and tobacco addiction in risk assessment.

BACKGROUND: rs4340ID polymorphism of angiotensin-converting enzyme (ACE) correlates with serum ACE levels in many known cancers. This study analyzed ACE rs4340 ID polymorphism in lung cancer (LC) in older patients of North India and correlated it with addiction status. METHODS: The study enrolled all subjects aged 60 years and above with 154 LC and 205 healthy controls. Genotyping was done by polymerase chain reaction (PCR) and validated by sequencing of 10% of the sample. Statistical analysis was done by SPSS Statistics 21. RESULTS: Genotype II was observed to have a significant 2.21-fold increased risk of LC as compared to the DD genotype and 3.43-folds enhanced risk with interaction of I allele with tobacco consumption habits as compared to D allele in LC was seen. CONCLUSION: The risk of LC was higher with II genotype as compared to DD genotype. Interactive effect showed that I allele with tobacco habits may increase the risk of LC.

Development and Psychometric Validation of a New Scale for Assessment and Screening of Frailty Among Older Indians.

BACKGROUND: Frailty is a major challenge for healthcare systems in ageing societies. This dynamic state of health is a reflection of reduced reserve in various organ systems and enhanced vulnerability to stressors. Research in this area of geriatrics and gerontology is limited in low- and middle-income countries (LMICs) like India. This study is directed at development of a culturally appropriate and validated assessment scale for frailty among older Indians. METHODS: After extensive review of the literature on existing scales, a preliminary draft scale was formed. This draft was pre- and pilot-tested to check feasibility and modified accordingly. The final scale was validated on 107 older adults by confirmatory factor analysis and was named the Frailty Assessment and Screening Tool (FAST). The Fried's frailty phenotype was also administered on the same 107 older adults and scores of both were co-related. Suitable cut-off scores were found for frail and pre-frail older adults. RESULTS: The final version of the FAST consisted of 14 questions pertaining to 10 domains. It has good reliability. Cronbach's alpha co-efficient was 0.99; test-retest reliability was 0.97 and validity by confirmatory factor analysis was adequate. The Kaiser-CMeyer-Olkin (KMO) of sampling adequacy was 0.699, and Bartlett's test of sphericity was significant (χ 2 = 353.471, p < 0.001). FAST scores had a cut-off of ≥ 7/14 for frail and ≥ 5/14 for pre-frail elderly. CONCLUSION: The FAST is a validated tool with good psychometric properties. It is expected that it will be helpful in screening pre-frail and frail older adults in India and other LMICs and guide in clinical decision making for intervention.

Implementing and validating a care protocol for older adults with cancer in resource limited settings with a newly developed screening tool.

BACKGROUND: Cancer in the aging population presents manifold challenges. In the resource-limited settings of developing countries, concrete steps to optimize care for older adults with cancer are required. MATERIALS AND METHOD: This prospective, observational study was divided in two parts. In the first part, older adults (≥60 years) with a tissue diagnosis of cancer underwent a preliminary, detailed assessment of relevant geriatric domains. The patients were followed up at 4, 12 and 24 weeks, and their survival status was recorded. In the second part a newly developed screening tool, "SCreening of the Older PErson with Cancer", Version1 (SCOPE-C) was validated on patients with similar characteristics. RESULTS: 419 participants were enrolled in the study. The mean age of the participants was 66.6 ± 6.2 years, 75% had functional impairment, 35% had malnutrition, and 64% had more than one co-morbidity. The median survival time was 22 weeks from the index visit. Male gender, functional decline, cognitive impairment, malnutrition, and treatment modality were found to be independently associated with survival. Individual Scores on the SCOPE-C Version1 scale were correlated with survival status at 24 weeks, and a cutoff score of 64 had a 72.2% sensitivity and 77.3% specificity for better prognosis. CONCLUSION: The present study is a comprehensive attempt to assess older adults with cancer with limited resources in a busy health system. A preliminary assessment with a prognostic screening tool may streamline care in resource-limited settings and aid clinicians in making treatment decisions.

Design and Methodology of the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (LASI-DAD).

BACKGROUND/OBJECTIVES: To provide high-quality data on older adults in India that will enable an in-depth study of late-life cognition and dementia in India and cross-country analysis of risk factors for cognitive aging and dementia. DESIGN: The Longitudinal Aging Study in India (LASI) is a nationally representative survey of health, economic, and social well-being of the Indian population aged 45 and older. Its large sample of more than 70,000 older adults represents not only the country as a whole but also each state. LASI-Diagnostic Assessment of Dementia (DAD) is an in-depth study of late-life cognition and dementia, drawing a subsample of over 3,000 LASI respondents aged 60 and older. SETTING: Participants were interviewed at home or in a participating hospital according to their preferences. PARTICIPANTS: Adults aged 60 and older (N = 3,224), along with 3,191 informants. MEASUREMENTS: Respondents underwent a battery of cognitive tests, and informants were interviewed about their cognitive and health conditions. A common set of cognitive tests was selected to enable international comparisons, and additional cognitive tests suitable for illiterate and innumerate populations were also selected. Rich data on risk factors of dementia were collected through health examination, venous blood assays, and genotyping. RESULTS: The response rate was 82.9%, varying across sex, education, and urbanicity. Data are available to other researchers. CONCLUSION: LASI-DAD provides an opportunity to study late-life cognition and dementia and their risk factors in the older population in India and to gain further insights through cross-country analysis by pooling data from its international sister studies. J Am Geriatr Soc 68:S5-S10, 2020.

Online Clinical Consensus Diagnosis of Dementia: Development and Validation.

OBJECTIVES: To introduce cost-effective expert clinical diagnoses of dementia into population-based research using an online platform and to demonstrate their validity against in-person clinical assessment and diagnosis. DESIGN: The online platform provides standardized data necessary for clinicians to rate participants on the Clinical Dementia Rating (CDR® ). Using this platform, clinicians diagnosed 60 patients at a range of CDR levels at two clinical sites. The online consensus diagnosis was compared with in-person clinical consensus diagnosis. SETTING: All India Institute of Medical Sciences (AIIMS), Delhi, and National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India. PARTICIPANTS: Thirty patients each at AIIMS and NIMHANS with equal numbers of patients previously independently rated in person by experts as CDR is 0 (cognitively normal), CDR is 0.5 (mild cognitive impairment), and CDR is 1 or greater (dementia). MEASUREMENTS: Multiple clinicians independently rate each participant on each CDR domain using standardized data and expert clinical judgment. The overall summary CDR is calculated by algorithm. When there are discrepancies among clinician ratings, clinicians discuss the case through a virtual consensus conference and arrive at a consensus overall rating. RESULTS: Online clinical consensus diagnosis based on standardized interview data provides consistent clinical diagnosis with in-person clinical assessment and consensus diagnosis (κ coefficient = 0.76). CONCLUSION: A web-based clinical consensus platform built on the Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India interview data is a cost-effective way to obtain reliable expert clinical judgments. A similar approach can be used for other epidemiological studies of dementia. J Am Geriatr Soc 68:S54-S59, 2020.

Association Between Episodic Memory and Genetic Risk Factors for Alzheimer's Disease in South Asians from the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (LASI-DAD).

BACKGROUND/OBJECTIVES: Genetic factors play an important role in Alzheimer's disease (AD) and cognitive aging. However, it is unclear whether risk loci identified in European ancestry (EA) populations have similar effects in other groups, such as South Asians. DESIGN: We investigated the allelic distribution and cognitive associations of 56 known AD risk single-nucleotide polymorphisms (SNPs) identified from three EA genome-wide association studies (EA-GWASs) in a South Asian population. Single SNP and genetic risk score (GRS) associations with measures of episodic memory were assessed. SETTING: The Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD). PARTICIPANTS: A total of 906 LASI-DAD participants from diverse states in India. MEASUREMENTS: Participants were genotyped using the Illumina Global Screening Array and imputed with 1000G Phase 3v5. Cognitive measures included total learning and delayed word recall. RESULTS: Although only a few SNPs were significantly associated with memory scores (P < .05), effect estimates from the EA-GWAS and the LASI-DAD showed moderate correlation (0.35-0.88) in the expected direction. GRSs were also associated with memory scores, although percentage variation explained was small (0.1%-0.6%). CONCLUSIONS: Discrepancies in allele frequencies and cognitive association results suggest that genetic factors found predominantly through EA-GWASs may play a limited role in South Asians. However, the extent of differences in the genetic architecture of AD and cognition in EA and South Asians remains uncertain. There is also a critical need to perform a more comprehensive assessment of the mutational spectrum of South Asia to identify novel genetic variants associated with AD and cognition in this population. J Am Geriatr Soc 68:S45-S53, 2020.

Review of health-care services for older population in India and possibility of incorporating AYUSH in public health system for geriatric care.

BACKGROUND: In a developing country like India, which has 10.11% population of >60 years age and a projection of rise of the same by 300% in 2050, health care of elderly is an enormous challenge. The developed world has evolved many models for elderly care, for example, nursing home care, health insurance, etc. Indian Government has also taken multiple measures in this direction by initiating National Policy on Older Persons, 1999, the Maintenance and Welfare of Parents and Senior Citizens Act, 2007, the Old Age Pension Scheme, Rashtriya Vayoshri Yojana 2017, etc. However, there is a necessity that, India must rapidly adapt to the complex health related, social and economic challenges caused by these demographic changes. This may be an opportunity for innovation in the health system by developing a perspective for healthy and active aging, though it is a major challenge. Health care of the older people cannot be achieved unless total health, i.e., physical, social, economic, psychological, and spiritual aspects are addressed. OBJECTIVE: The objective is to study current policies regarding geriatric health care in India and to propose the possibility to develop a model to provide comprehensive and dedicated health-care services to the older population by integrating conventional and indigenous systems of medicine dwelling in the country. MATERIALS AND METHODS: Electronic search in various scientific journals for research and review articles; electronic along with hand searching of conference proceedings, brochures, government policy documents, press releases, Ayurveda classical texts, etc., regarding geriatric health care in India and model health-care facilities in other countries and regarding of AYUSH systems in geriatric health care in India. RESULTS: There is an urgent need of adaptation and modification in the National Health System to cater the actual requirements of the elderly with plans and strategies dedicated to face their health-related challenges. Adoption of inclusive health-care interventions, can improve health outcomes by making it more acceptable, accessible, and affordable. CONCLUSION: Integration of AYUSH at various levels of health-care delivery system can potentially contribute to provide unique newer dimensions to the field of geriatric care in India.

Effect of deep tissue laser therapy treatment on peripheral neuropathic pain in older adults with type 2 diabetes: a pilot randomized clinical trial.

BACKGROUND: This study assessed the safety and efficacy of deep tissue laser therapy on the management of pain, functionality, systemic inflammation, and overall quality of life of older adults with painful diabetic peripheral neuropathy. METHODS: The effects of deep tissue laser therapy (DTLT) were assessed in a randomized, double-masked, sham-controlled, interventional trial. Forty participants were randomized (1:1) to receive either DTLT or sham laser therapy (SLT). In addition to the standard-of-care treatment, participants received either DTLT or SLT twice weekly for 4 weeks and then once weekly for 8 weeks (a 12-week intervention period). The two treatments were identical, except that laser emission was disabled during SLT. Assessments for pain, functionality, serum levels of inflammatory biomarkers, and quality of life (QOL) were performed at baseline and after the 12-week intervention period. The results from the two treatments were compared using ANOVA in a pre-test-post-test design. RESULTS: All participants randomized to the DTLT group and 85% (17 of 20) of participants randomized to the SLT group completed the trial. No significant differences in baseline characteristics between the groups were observed. After the 12-week intervention period, pain levels significantly decreased in both groups and were significantly lower in the DTLT group than in the SLT group. The Timed Up and Go test times (assessing functionality) were significantly improved in both groups and were 16% shorter in the DTLT group than in the SLT group. Serum levels of IL-6 decreased significantly in both groups. Additionally, serum levels of MCP-1 decreased significantly in the DTLT group but not in the SLT group. Patients' quality of life improved significantly in the DTLT group but not in the SLT group. CONCLUSIONS: Deep tissue laser therapy significantly reduced pain and improved the quality of life of older patients with painful diabetic peripheral neuropathy. TRIAL REGISTRATION: Clinical Trial Registry-India CTRI/2017/06/008739 . [Registered on: 02/06/2017]. The trial was registered retrospectively.

Development of integrated care tool - BRIEF for screening the unmet psychosociomedical needs of older Indians.

BACKGROUND: With demographic shifts, there is an unprecedented increase in noncommunicable diseases, multimorbidity, and geriatric syndromes among older adults, especially in economically weaker sectors. However, there is no socioculturally appropriate tool to screen older adults for age-related health needs, multimorbidity, and geriatric syndromes at their doorstep. Objective: Our objective was to create a self-assessment tool, "integrated care tool" (ICT), and to assess its psychometric properties by applying it on older adults from multiple settings such as hospital, community, and old-age home (assisted living services). METHODS: new questionnaire was developed using standardized procedure including item development, pilot testing, and psychometric validation. After obtaining the institutional ethics committee clearance, data were collected from consenting respondents attending the Outpatient Department of Geriatric Medicine, All India Institute of Medical Sciences, New Delhi, community settings through health camps, and long-term care center, between May 2016 and February 2017. Data were computerized and analyzed by principal component analysis as extraction method and orthogonal varimax as rotation method. RESULTS: The final 30-item questionnaire was arranged into various domains as per rotated component matrix analysis. Overall internal consistency of the final questionnaire, as calculated by Cronbach's alpha, was 0.79, and the measure of sampling adequacy was 0.79. CONCLUSION: ICT-BRIEF is a simple, self-assessment/caregiver-assisted tool to screen the health needs of older adults. This tool can be validated for developing risk score and scaled up to generate a large database to create elderly centered care plans.

Exploration of Novel Anti-Oxidant Protein Sestrin in Frailty Syndrome in Elderly.

Frailty in elderly is very much familiar with a decline in the musculoskeletal system. Muscle degeneration in the lower organism was observed due to loss of anti-oxidant protein Sestrin. The aim of the study is to determine the level of Sestrin1 and Sestrin2 in the serum of frail and non-frail elderly to associate their impact in frailty syndrome. Subjects with age ≥ 65 years were enrolled from Geriatric Medicine OPD of All India Institute of Medical Sciences, New Delhi (N= 92). Among them, 51 subjects were identified as frail and rest 41 were regarded as non-frail according to "deficit accumulation model of Rockwood." The study was performed by surface plasmon resonance and validated by western blot. Sestrin1 and Sestrin2 were found to be significantly reduced in frail compare to non-frail elderly. Furthermore, even after the adjustment for age, gender and education, the level of Sestrin1 and Sestrin2 remain significantly lower across the groups. The Sestrin1 level was significantly lower in various categories like age, gender, BMI, education, ADL, number of co-morbidity along with other clinico-pathological features. ROC analysis also revealed the distinction of frail and non-frail in respect to serum Sestrin1 and Sestrin2. This study highlighted the new and promising role of serum Sestrin in frail and non-frail elderly. In future, it can be utilized as molecular marker to assess the potential diagnostic value for clinical purpose.

Serum Mortalin Correlated with α-Synuclein as Serum Markers in Parkinson's Disease: A Pilot Study.

Mortalin, a mitochondrial chaperone, plays a crucial role in reducing toxicity of Lewy bodies. Earlier studies had reported that Mortalin level gets downregulated in astrocytes and other brain tissue samples in Parkinson's disease (PD). This study aims to estimate the Mortalin concentration in serum and correlate with α-synuclein (α-Syn) in PD. The concentration of Mortalin and α-Syn in serum samples of 38 PD patients and 33 control group (CG) individuals was quantified by surface plasmon resonance. The receiver operating characteristic curves were plotted to develop it as blood-based protein marker. The expression of Mortalin in serum was validated by western blot. The Mortalin level was found to be declined in PD patients (1.98 ± 0.53 ng/µL) in comparison with CG individuals (3.13 ± 0.48 ng/µL), whereas α-Syn level was found to be elevated in PD patients (38.20 ± 4.22 ng/µL) than CG individuals (34.31 ± 3.23 ng/µL) in serum. The statistical analysis revealed the negative correlation between Mortalin and α-Syn. This preliminary study summarized that Mortalin plays a significant role in PD with negative correlation with α-Syn. This study provides a new paradigm for the development of Mortalin as a potent serum protein marker for diagnosis of PD.

5-LOX in Alzheimer's Disease: Potential Serum Marker and In Vitro Evidences for Rescue of Neurotoxicity by Its Inhibitor YWCS.

The inflammatory process plays a key role in neurodegenerative disorder. The inflammatory molecule, 5-lipooxygenase (5-LOX), protein is involved in the pathologic phenotype of Alzheimer's disease (AD) which includes Aß amyloid deposition and tau hyperphosphorylation. This study determined the level of 5-LOX in serum of AD patients, mild cognitive impairment (MCI) patients, and the normal elderly, and the rescue effect by YWCS, a peptide inhibitor of 5-LOX on neurotoxicity by Aß amyloid25-35 (Aß25-35) in neuroblastoma cells. The concentration of serum 5-LOX was estimated by surface plasmon resonance and western blot. The neuroprotective effect of 5-LOX peptide inhibitor YWCS in Aß25-35-induced neurotoxicity was analyzed by MTT assay and western blotting. We found significant upregulated serum 5-LOX in AD patients and also in MCI patients compared to the normal control group. The peptide inhibitor of 5-LOX, YWCS, prevented the neurotoxic effect of Aß25-35 by reducing the expression of γ-secretase as well as p-Tau181 in SH-SY5Y cells. However, YWCS was nontoxic towards normal HEK cells. The differential expression of serum 5-LOX among the study groups suggests it can be one of potential serum protein marker and a therapeutic regimen for AD and MCI. The negative correlation with neuropsychological parameters, i.e., MoCA and HMSE, increases its importance and makes it useful during the clinical setup which is very needful in developing countries. Peptide YWCS can serve as a new platform as a 5-LOX inhibitor which can prevent neurotoxicity developed in AD.

Longevity and healthy ageing genes FOXO3A and SIRT3: Serum protein marker and new road map to burst oxidative stress by Withania somnifera.

BACKGROUND: Ageing process is characterized by a decline in function; different age related diseases and excessive age associated mortality. There has always been a quest for easily accessible biomarkers to monitor and identify the development of age-associated stress for providing new anti-ageing strategies. Forkhead box protein O3A (FOXO3A) and Sirtuin3 (SIRT3) are such potential markers which plays important role in a wide variety of cellular mechanisms and has been proposed to be an ideal candidate to study longevity and are potential candidate for healthy ageing by oxidative burst. OBJECTIVES: In this study we quantified FOXO3A and SIRT3 proteins in human serum with increasing age and in-vitro assessment of modulation of their expression by the treatment of Withania somnifera (Ashwagandha). METHODOLOGY: Four hundred seventy three subjects were enrolled for the study and were divided into three groups according to increasing age [20-30years (young), 60-79years (old) and ≥80years (oldest)]. Serum levels of FOXO3A and SIRT3 proteins were estimated by Surface Plasmon Resonance (SPR) and validated by ELISA and Western blot. The statistical analysis was done with student's unpaired t-test, one way ANOVA by Stata9 and Graph pad prism5. The expression of these proteins were also analysed in stress induced HEK-293 cell line and level was observed by treatment with stress releasing compound Ashwagandha. RESULTS: In this cross sectional observational study, the serum concentration of FOXO3A and SIRT3 declined significantly (p<0.0001) with increasing age and even after adjustment with all geriatric co-morbidities the level remain downregulated with age. In the stress inducible cell line showed reduced level of proteins which gets upregulated by the treatment of Ashwagandha. CONCLUSION: This is the first report of inverse relation of age with human serum FOXO3A and SIRT3 and can be excellent marker for ageing with good therapeutic importance for maintaining healthy ageing.

Relative Alterations in Blood-Based Levels of Sestrin in Alzheimer's Disease and Mild Cognitive Impairment Patients.

Sestrins (sesn) are highly conserved proteins that play an important neuroprotective role, in part as a consequence of their antioxidative capacity, which prevents reactive oxygen species formation. In this study, we evaluated the concentrations of sesn1 and sesn2 in the serum of 41 Alzheimer's disease (AD) patients, 27 mild cognitive impairment (MCI), and 60 elderly controls, by surface plasmon resonance, which was validated by using western blot. Moreover, the mRNA level of sestrins in all the study groups was determined by real time polymerase chain reaction. The results showed significant overexpression of serum sesn2 protein and mRNA levels in the AD group compared to MCI and elderly control groups. A difference in serum sesn2 concentration between MCI and the control group was also evident. ROC analysis showed highly sensitive, selective cutoff values for sens2 in the differentiation of AD, MCI, and controls. No significant difference in sesn1 level was observed among the study groups. This study highlights the important role of sesn2 in the progression of the AD, indicating its potential utility as a protein marker in this devastating disease.

Estimation of Tau and Phosphorylated Tau181 in Serum of Alzheimer's Disease and Mild Cognitive Impairment Patients.

The elevated level of cerebrospinal fluid (CSF) Tau and phosphorylated Tau181 (p-Tau181) proteins are well established hallmarks of Alzheimer's disease (AD). Elevated level of p-Tau181 can differentiate AD from other neurodegenerative disease. However, the expression level of these proteins in serum of AD patient is not well set up. This study sought to evaluate the level of Tau and p-Tau181 in serum of AD, and mild cognitive impairment (MCI) patients for an alternative approach to establish protein-based markers by convenient way. Blood samples were collected from 39 AD patients, 37 MCI patients and 37 elderly individuals as controls. The levels of Tau and p-Tau181 in the serum of the different groups were measured by label free real time Surface Plasmon Resonance technology by using specific antibodies, and were further confirmed by the conventional western blot method. An appropriate statistical analysis, including Receiver Operating Characteristic (ROC), was performed. The concentrations of serum Tau and p-Tau181 were significantly higher (p<0.00001) in AD (Tau; 47.49±9.00ng/µL, p-Tau181; 0.161±0.04 ng/µL) compared to MCI (Tau; 39.26±7.78 ng/µL, p-Tau181; 0.135±0.02 ng/µL) and were further higher compared to elderly controls (Tau; 34.92±6.58 ng/µL, p-Tau181; 0.122±0.01 ng/ µL). A significant (p<0.0001) downhill correlation was found between Tau as well as p-Tau181 levels with HMSE and MoCA score. This study for the first time reports the concentration of Tau and p-Tau181 in serum of AD and MCI patients. The cutoff values of Tau and p-Tau181 of AD and MCI patients with sensitivity and specificity reveal that serum level of these proteins can be used as a predictive marker for AD and MCI.