Circulating small extracellular vesicles in Alzheimer's disease: a case-control study of neuro-inflammation and synaptic dysfunction.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease characterized by Aß 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-ß 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-1ß, and GFAP antibodies. AD-specific markers, amyloid-ß (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-ß (1-42) expression within PsEVs is significantly elevated in MCI and AD compared to AMC. We could also differentiate between the amyloid-ß (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-1ß, 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-ß (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.

Prevalence of dementia in India: National and state estimates from a nationwide study.

INTRODUCTION: Prior estimates of dementia prevalence in India were based on samples from selected communities, inadequately representing the national and state populations. METHODS: From the Longitudinal Aging Study in India (LASI) we recruited a sample of adults ages 60+ and administered a rich battery of neuropsychological tests and an informant interview in 2018 through 2020. We obtained a clinical consensus rating of dementia status for a subsample (N = 2528), fitted a logistic model for dementia status on this subsample, and then imputed dementia status for all other LASI respondents aged 60+ (N = 28,949). RESULTS: The estimated dementia prevalence for adults ages 60+ in India is 7.4%, with significant age and education gradients, sex and urban/rural differences, and cross-state variation. DISCUSSION: An estimated 8.8 million Indians older than 60 years have dementia. The burden of dementia cases is unevenly distributed across states and subpopulations and may therefore require different levels of local planning and support. HIGHLIGHTS: The estimated dementia prevalence for adults ages 60+ in India is 7.4%. About 8.8 million Indians older than 60 years live with dementia. Dementia is more prevalent among females than males and in rural than urban areas. Significant cross-state variation exists in dementia prevalence.

Evidence of Economically Sustainable Village-Scale Microenterprises for Arsenic Remediation in Developing Countries.

Although unknown 25 years ago, natural arsenic contamination of groundwater affects over 50 countries and up to 200 million people. The economic viability was analyzed and modeled of eighty-eight community-based arsenic mitigation systems existing for up to 20 years in India and Bangladesh. The performances of three community-based arsenic mitigation systems that are ethnically different and separated across two different countries were monitored closely for 24 months of self-sustainable, long-term operation at WHO standards through local, paid caretakers. Based on data from the use of hybrid ion exchange materials (HIX-Nano) and the broad set of field operations, Monte Carlo simulations were used to explore the conditions required for self-sustainable operation and job creation in low-income communities (<$2/day/capita). The results from field data and cost modeling provided clear evidence of economic growth and job creation for systems managed by villagers' committee through collection of monthly tariffs. Ethnicity and religion did not have perceptible impacts on day-to-day operations or cumulative long-term revenue. The cost of the treatment technology (i.e., HIX-Nano) had minimal impact on the operational profitability, while number of customers and water delivery significantly affected profitability. Local employment generation with income significantly higher than poverty level was the most enduring outcome and led to enhanced sustainability.

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.

Nordic walking training and nutritional supplementation in pre-frail older Indians: an open-labelled experimental pre-test and post-test pilot study to develop intervention model.

BACKGROUND: Identifying and treating people in a pre-frail state may be an effective way to prevent or delay frailty and preserve their functional capacity. This study aimed to assess the efficacy of, and compliance with, a 12 week individualized nutritional supplementation (INS) and Nordic walking (NW) program in pre-frail older Indians. The primary measure is physical performance, as indicated by Fried's Frailty scale. Other measures include: cognition, as indicated by the Hindi Mental Status Examination; mood, by the Geriatric Depression Scale; and nutritional status, by the Mini Nutritional Assessment. METHODS: This is an open-labeled experimental pre-test and post-test study, which took place from October 2012 to December 2014. The study was approved by Institute Ethics committee (IEC/NP-350/2012/RP-26/2012) at the All India Institute of Medical Sciences (AIIMS), New Delhi. Participants were sixty-six pre-frail elderly, who were randomly allocated into three subgroups, namely: A (NW only), B (INS only), and C (NW and INS). One-way ANOVA was used to statistically assess differences in baseline characteristics for quantitative variables, with the Chi-Square/Fischer exact test utilized for qualitative variables. Paired t-tests were used to assess pre and post intervention difference within the group for quantitative variables, with McNemar's Chi-Square test used for qualitative variables. Kruskal Wallis test was used to assess significant intervention effects among the groups. A p-value < 0.05 was considered as statistically significant. RESULTS: There was significant effect of intervention in gait speed in group A (p = 0.001) and C (p = 0.002), but not in group B (p = 0.926). While there was no significant change in grip strength in Group A (p = 0.488) and B (p = 0.852), a statistically significant increase was observed in group C (p = 0.013). Mood significantly improved in group B (p = 0.025) and C (p = 0.021). No significant difference was noted in cognitive status across groups. Following the interventions, a total of 18.18% of pre-frail participants were classified as non-frail. CONCLUSIONS: Combining NW and INS provides a simple, pragmatic intervention with efficacy in the management of functionally vulnerable older adults, and allows their maintained independence. Future studies should replicate this readily applicable intervention in a larger cohort with a longer follow-up period. TRIAL REGISTRATION: Clinical Trial Registry-India CTRI/2016/05/006937 [Registered on: 16/05/2016]; Trial was Registered Retrospectively.

Factors Associated with Subjective Aging Among Older Outpatients In Northern - India.

Objectives: The objective of the study was to investigate factors associated with subjective aging among older patients visiting a geriatric medicine outpatient department in Northern-India. Methods: The study is a cross-sectional study. Patients were categorized into three groups: whether they felt younger, equal, or older than their peers of same age. Factors such as fall, incontinence, anorexia, hand grip strength, cognition, depression, vision, hearing, cardiopulmonary function and immunization were assessed. Multinominal logistic regression was used to investigate the associated factors of subjective aging. Results: We assessed 184 older patients with a median age of 66.5 years (IQR 63.0 -78.8). Chronological age and hand grip strength were the significant factors associated with subjective aging. With one year increase in age, odds of feeling older than peers of same age decreased by 8.9% (OR, 0.911; 95% CI, 0.831-0.999, p = 0.047). With one kilogram increase in hand grip strength, odds of feeling younger than peers of same age increased by 7.3% (OR, 1.073; 95% CI, 1.01-1.14, p = 0.032). Conclusion: Chronological age and hand grip strength are the factors associated with subjective aging in Northern-Indian older adults. Further longitudinal multi-center studies are needed to confirm our findings.

The evaluation of frequency and predictors of delirium and its short-term and long-term outcomes in hospitalized older adults'.

BACKGROUND: Delirium is a common complication in hospitalized older adults with multifactorial etiology and poor health outcomes. AIM: To determine the frequency and predictors of delirium and its short-term and long-term outcomes in hospitalized older adults. METHODS: A prospective observational study was performed in patients aged ≥60 years consecutively admitted to geriatric ward. Potential risk factors were assessed within 24 hours of hospital admission. Delirium screening was performed on admission and daily thereafter throughout the hospital stay using Confusion Assessment Method (CAM). Patients were followed up at 1-year post-discharge. RESULTS: The study included 200 patients with mean age 73.1 ± 8.83 years. Incidence and prevalence rate of delirium were 5% and 20% respectively. Multivariable regression analysis revealed emergency admission (OR= 5.12 (1.94-13.57), p=0.001), functional dependency (Katz index of Independence in Activities of Daily Living (Katz-ADL) score <5) 2 weeks before admission (OR= 3.08 (1.30-7.33), p=0.011) and more psychopathological symptoms (higher Brief Psychiatric Rating Scale (BPRS) total score) (OR=1.12 (1.06-1.18), p=0.001) to be independently associated with delirium. Patients in delirium group had significantly high in-hospital mortality (OR= 5.02 (2.12-11.8), p=0.001) and post-discharge mortality (HR= 2.02 (1.13-3.61), p=0.017) and functional dependency (Katz-ADL score <5) (OR= 5.45 (1.49-19.31), p=0.01) at 1-year follow up. CONCLUSION: Delirium is quite frequent in geriatric inpatients and is associated with high in-hospital and post-discharge mortality risk and long-term functional dependency. Emergency admission, pre-hospitalization functional dependency, and more general psychopathological symptoms are independently associated factors. Hence, earliest identification and treatment with early implementation of rehabilitation services is warranted.

Clinical and neuropsychological characterization of SuperAgers residing in Delhi and National Capital Region of India-A cross-sectional study.

Introduction: SuperAgers (SA) are older adults who exhibit cognitive capacities comparable to individuals who are three or more decades younger than them. The current study aimed to identify the characteristics of Indian SA by categorizing 55 older adults into SA and Typical Older Adults (TOA) and comparing their performance with a group of 50 younger participants (YP) (aged 25-50). Methods: A total of 105 participants were recruited after obtaining informed written consent. The cognitive abilities of the participants were assessed using Wechsler Adult Intelligence Scale (WAIS)-IVINDIA, Color Trails Test, Boston Naming Test (BNT), and Rey Auditory Verbal Learning Test. Results: SA outperformed TOA in all cognitive assessments (P < 0.001) and surpassed YP in BNT and WAIS-IV. SA's delayed recall scores were notably higher (12.29 ± 1.51) than TOA (6.32 ± 1.44). Conclusion: SA excelled in all cognitive domains demonstrating resilience to age-related cognitive decline. This study highlights Indian SuperAgers' exceptional cognitive prowess.

Quantification of COX-2 Level in Alzheimer's Disease Patients to Develop Potential Blood-Based Biomarker for Early Diagnosis and Therapeutic Target.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease and symptoms develop gradually over many years. The current direction for medication development in AD is focused on neuro-inflammation and oxidative stress. Amyloid-ß (Aß) deposition activates microglia leading to neuro-inflammation and neurodegeneration induced by activation of COX-2 via NFκB p50 in glioblastoma cells. Objective: The study aimed to evaluate the concentration of COX-2 and NFκB p50 in serum of AD, mild cognitive impairment (MCI), and geriatric control (GC) and to establish a blood-based biomarker for early diagnosis and its therapeutic implications. Methods: Proteins and their mRNA level in blood of study groups were measured by surface plasmon resonance (SPR) and quantitative polymerase chain reaction (qPCR), respectively. The level of protein was further validated by western blot. The binding study of designed peptide against COX-2 by molecular docking was verified by SPR. The rescue of neurotoxicity by peptide was also checked by MTT assay on SH-SY5Y cells (neuroblastoma cell line). Results: Proteins and mRNA were highly expressed in AD and MCI compared to GC. However, COX-2 decreases with disease duration. The peptide showed binding affinity with COX-2 with low dissociation constant in SPR and rescued the neurotoxicity of SH-SY5Y cells by decreasing the level of Aß, tau, and pTau proteins. Conclusions: It can be concluded that COX-2 protein can serve as a potential blood-based biomarker for early detection and can be a good platform for therapeutic intervention for AD.

Gait Parameters Change can be an Early Marker of Cognitive Impairment.

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.

Predictors of Survival Among the Oldest Old Following Acute Hospital Admission: Insights From Clinical and Biochemical Factors.

Understanding the factors influencing survival in oldest old population is crucial for providing appropriate care and improving outcomes. This prospective observational study aimed to investigate the determinants of survival in acutely ill oldest old patients during acute hospitalization and 1-month follow-up. Various geriatric domains and biochemical markers were assessed. Among the 70 included patients with a median age of 87 (Inter quartile range: 85-90), the presence of diabetes, delirium, tachypnea, and high sirtuin-5 levels were associated with reduced in-hospital survival. Non-survivors had raised levels of Sirtuin 1 and Sirtuin 5, with an increase of 43% and 70%, respectively. At 1 month, delirium and diabetes were still associated with reduced survival. These findings suggest that type-2 diabetes, delirium, tachypnea, and high sirtuin-5 levels could serve as predictors of reduced survival in acutely ill, hospitalized oldest old patients.

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.

Deep phenotyping and genomic data from a nationally representative study on dementia in India.

The Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) is a nationally representative in-depth study of cognitive aging and dementia. We present a publicly available dataset of harmonized cognitive measures of 4,096 adults 60 years of age and older in India, collected across 18 states and union territories. Blood samples were obtained to carry out whole blood and serum-based assays. Results are included in a venous blood specimen datafile that can be linked to the Harmonized LASI-DAD dataset. A global screening array of 960 LASI-DAD respondents is also publicly available for download, in addition to neuroimaging data on 137 LASI-DAD participants. Altogether, these datasets provide comprehensive information on older adults in India that allow researchers to further understand risk factors associated with cognitive impairment and dementia.

A rare case of late-onset limb-girdle muscular dystrophy: Calpainopathy.

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.

Establishment of Clinical Construct of Intrinsic Capacity in Older Adults and Its Prediction of Functional Decline.

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.

Association of geriatric syndromes in older adults with chronic obstructive pulmonary disease.

Background: Geriatric syndromes (GS) are multi-factorial conditions that make older adults vulnerable to morbidities and poor outcomes. The main objective was to observe the frequency of GS in older patients with COPD. Methods: A case-control study was conducted in the Geriatric department of a tertiary care hospital in India to evaluate geriatric syndromes including falls, cognitive impairment, frailty, functional impairment, urinary incontinence, malnutrition, and depression in patients with COPD and controls without COPD. The factors having a significant association with the occurrence of these GS in COPD patients were observed. Results: In this study, 150 cases and 150 controls were included. The mean age of the participant was 65.85±5.54, with 76% males. Functional impairment, cognitive impairment, frailty, urinary incontinence, and malnutrition were significantly higher in COPD patients. The independent variables which increased the odds of geriatric syndromes were dyspnoea (≥2 mMRC grade) (AOR:3.54,95% CI:1.06-11.8) and low socioeconomic status (AOR: 4.14, 95% CI: 1.03-16.54), while male gender showed inverse association (AOR: 0.08,95% CI: 0.01-0.99). Conclusion: Geriatric syndromes are common in older COPD patients, and assessment for them should be done routinely in these patients.

Blood Circulatory Level of Seven Sirtuins in Alzheimer's Disease: Potent Biomarker Based on Translational Research.

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.

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.

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.