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.

Defining anthropometric thresholds (mid-arm circumference and calf circumference) in older adults residing in the community: a cross-sectional analysis using data from the population representative Longitudinal Aging Study in India (LASI DAD).

OBJECTIVES: To identify factors associated with malnutrition (undernutrition and overnutrition) and determine appropriate cut-off values for mid-arm circumference (MAC) and calf circumference (CC) among community-dwelling Indian older adults. DESIGN: Data from the first wave of harmonised diagnostic assessment of dementia for Longitudinal Ageing Study in India (LASI-DAD) were used. Various sociodemographic factors, comorbidities, geriatric syndromes, childhood financial and health status were included. Anthropometric measurements included body mass index (BMI), MAC and CC. SETTING: Nationally representative cohort study including 36 Indian states and union territories. PARTICIPANTS: 4096 older adults aged >60 years from LASI DAD. OUTCOME MEASURES: The outcome variable was BMI, categorised as low (<18.5 kg/m2), normal (18.5-22.9 kg/m2) and high (>23 kg/m2). The cut-off values of MAC and CC were derived using ROC curve with BMI as the gold standard. RESULTS: 902 (weighted percentage 20.55%) had low BMI, 1742 (44.25%) had high BMI. Undernutrition was associated with age, wealth-quintile and impaired cognition, while overnutrition was associated with higher education, urban living and comorbidities such as hypertension, diabetes and chronic heart disease. For CC, the optimal lower and upper cut-offs for males were 28.1 cm and >31.5 cm, respectively, while for females, the corresponding values were 26 cm and >29 cm. Similarly, the optimal lower and upper cut-offs for MAC in males were 23.9 cm and >26.9 cm, and for females, they were 22.5 cm and >25 cm. CONCLUSION: Our study identifies a high BMI prevalence, especially among females, individuals with higher education, urban residents and those with comorbidities. We establish gender-specific MAC and CC cut-off values with significant implications for healthcare, policy and research. Tailored interventions can address undernutrition and overnutrition in older adults, enhancing standardised nutritional assessment and well-being.

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.

Association Between Cognitive Performance and Nutritional Status: Analysis From LASI-DAD.

Malnutrition in low- and middle-income countries causes cognitive decline and other health problems. Harmonized Diagnostic Assessment of Dementia for Longitudinal Aging Study in India (LASI DAD) is an extensive study on late-life cognition and dementia. This study examines the link between nutrition and cognitive abilities in older adults using data from the LASI DAD. We conducted descriptive statistics on nutritional parameters (body-mass index, waist-hip ratio, and Mini-Nutritional Assessment), cognitive functions, and socio-demographic variables in 2,892 adults aged ≥60 years. Cognitive domains assessed included delayed recall, orientation, language, executive function, abstract reasoning, and attention. Cognitive impairment was defined as impaired performance in two or more domains. Mean age was 69.3 ± 7.1 years, 52.9% were female, and 57.5% were illiterate. Low body-mass index (adjusted OR: 1.88, p < .001), at risk of malnutrition (adjusted OR: 1.89, p < .001) and malnourished (adjusted OR: 2.86, p < .001) on Mini-Nutritional Assessment were associated with the presence of cognitive impairment. Better cognitive performance was associated with increased body mass index (adjusted OR: 0.74, p-.03), hemoglobin (adjusted OR: 0.91, p-.006), and serum albumin (adjusted OR: 0.38, p < .001). This study shows that nutritional status assessed by anthropometric measures and blood markers is strongly linked to cognitive performance in older adults.

The prevalence of frailty and its relationship with sociodemographic factors, regional healthcare disparities, and healthcare utilization in the aging population across India.

Objective: To estimate frailty prevalence and its relationship with the socio-economic and regional factors and health care outcomes. Methods: In this study, participants from the harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) were included. The frailty index (FI) was calculated using a 32-variable deficit model, with a value of ≥ 25% considered as frail. Data on demographic (including caste and religion) and socioeconomic profiles and health care utilization were obtained. The state-wise health index maintained by the government based on various health-related parameters was used to group the participants' residential states into high-, intermediate-, and low-performing states. Multivariable and zero-inflated negative binomial regression was used to assess the relationship of frailty index with sociodemographic characteristics, health index, and health care expenditure or hospitalization. Results: Among the 3953 eligible participants, the prevalence of frailty was 42.34% (men = 34.99% and women = 49.35%). Compared to high-performing states, intermediate- and low-performing states had a higher proportion of frail individuals (49.7% vs. 46.8% vs. 34.5%, P < 0.001). In the adjusted analysis, frailty was positively associated with age, female sex, rural locality, lower education level, and caste (scheduled caste and other backward classes). After adjusting for the socio-economic profile, FI was inversely associated with the composite health index of a state (P < 0.001). FI was also significantly correlated with total 1-year health care expenditure and hospitalization (P < 0.001 and 0.020, respectively). Conclusion: There is a high prevalence of frailty among older Indian adults that is associated with sociodemographic factors and regional health care performance. Furthermore, frailty is associated with increased health care utilization and expenditure.

Recurrent syncope in long survivors and its association with geriatric syndromes.

Objective: Syncope is a common clinical condition in the elderly, associated with significant morbidity and risk of recurrence. Recurrent syncope causing a repeated reduction in the cerebral blood flow can predispose to progressive neurodegeneration, a decline in overall health and functionality. Hence, this study was conducted to study the common causes of recurrent syncope and its association with various geriatric syndromes. Methodology: This case-control study recruited 50 cases of recurrent syncope and 50 controls, aged 75 years and older. A detailed history and sequential evaluation for aetiologies of recurrent syncope were done. Cognition, frailty, activities of daily living, depression, and nutrition were assessed using various scales. Results: Most (80%, 80/100) of the participants were males and the mean age was 80.04 ± 4.3 years. In the syncope group, 42% (21/50) of patients had arrhythmia, and 30% (15/30) had valvular heart disease. Recurrent syncope was significantly associated with lower scores on Montreal cognitive assessment scale (OR: 6.47 P < 0.001), four or more comorbidities (OR: 6.29 P < 0.001), and hearing impairment (OR: 6.21 P < 0.004) on multivariate logistic regression analysis. Conclusion: Recurrent syncope is significantly associated with cognitive impairment, the presence of four or more comorbidities, and hearing impairment. Conduction abnormality was the most common etiology of recurrent cardiovascular syncope. Structured evaluation and appropriate management of recurrent syncope might reduce the decline in physical, cognitive, and psychological reserve. A follow-up longitudinal study is needed to establish this.

Investigating the factors that explain white matter hyperintensity load in older Indians.

White matter hyperintensities are areas of hyperintense signal on MRI that typically represent cerebrovascular pathology. While focal white matter hyperintensities are common among older individuals, extensive white matter hyperintensities have been found to accelerate the progression of dementia. However, little is currently known about how various socioeconomic, health, lifestyle and environmental factors affect the severity of these lesions, particularly in low- and middle-income countries such as India. We investigated this question using cross-sectional MRI data (n = 126) from a pilot neuroimaging sub-study of an ongoing, nationally representative epidemiological study of late-life cognition in India. As a screening step, we estimated white matter hyperintensity load from fluid-attenuated inversion recovery MRI using a fully automated technique and tested for associations with each factor separately, controlling for age, sex and estimated total intracranial volume in each case. A combined model of white matter hyperintensity load included five factors which were significant after multiple comparisons correction: systolic blood pressure, body mass index, urbanicity status (urban versus rural living), daily chore hours and the frequency of store trips. This model explained an additional 27% of the variance in white matter hyperintensity load (54 versus 27% for the baseline model with only age, sex and estimated total intracranial volume). We accounted for the possibility of reverse causality by additionally controlling for concurrent markers of neurodegeneration and cognitive impairment, with no substantial change in our findings. Overall, our findings suggest that controlling high blood pressure and maintaining both a healthy body mass index and high levels of physical activity may reduce white matter hyperintensity load in older Indian adults, helping to prevent or delay dementia.

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.

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.

Discrepancy in Fluid and Crystallized Intelligence: An Early Cognitive Marker of Dementia from the LASI-DAD Cohort.

Background: Cognitive aging is a complex phenomenon, which comprises various cognitive skills, broadly categorized into fluid and crystallized intelligence. Crystallized intelligence (gc) tends to be maintained, as opposed to fluid intelligence (gf), which tends to decline rapidly with age. The association of the two with cognitive decline remains a matter of conjecture requiring further research. Aim: The aim of the study was to identify the variables of gc and gf from a population data of Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (LASI-DAD) study and investigate its relationship with the onset of cognitive impairment using discrepancy analysis against neuropsychological tests. Methods: This analysis of data from LASI-DAD study was carried out on a sample of 3,223 participants. They were assessed on extensive thirteen cognitive tests and one subjective test of cognition. Standardized score was used for discrepancy analysis. Fluid ability minus crystallized ability was used to assess the cognitive impairment. Any statistical significance with the score difference >0.99 SD was defined as a presence of cognitive decline. Hindi Mental Status Examination (HMSE) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) were used as gold standard. Results: With increased discrepancy score, each cognitive parameter score declined which was found to be statistically significant. In HMSE (Normal = 25.81 ± 3.39; Impaired = 23.17 ± 3.54; p = <0.001), there was a drop of 2 point scores in identifying cognitive impairment in the population sample as per the gold standard. A similar trend was evident in other neurocognitive domains as well. Conclusion: Crystallized-fluid intelligence discrepancy analysis has a strong potential in predicting the onset of cognitive decline ahead of time, facilitating early intervention.

Six-minute walk test and its predictability in outcome of COVID-19 patients.

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.

Characterization of potentially inappropriate medications use in Indian elderly population and their impact on quality of life using Beers criteria.

Background: Polypharmacy is principal cause of potentially inappropriate medications (PIMs) in elderly patients, which include over prescribing, under prescribing, and misprescribing. Methods: Elderly subjects (≥60 years), of either sex, receiving two or more medications for one or more chronic ailments, attending Geriatrics Outpatient Department (OPD), at All India Institute of Medical Sciences (AIIMS) New Delhi, were included. Their prescriptions were assessed for PIMs by using Beers criteria 2015 and were further followed up at least once in 6 months for adverse events, telephonically. The results were analyzed by using suitable regression models and correlation analysis. Results: Three hundred eighty patients average age of 65.4 ± 4.7 years were enrolled. Eighty-eight percent of the people were having greater than or equal to two ailments. Each patient was prescribed 6.7 ± 2.1 medications with 65% of prescriptions having one or more PIMs. Out of the total prescribed drugs, 15% were satisfying Beers criteria for PIMs. There were 63 adverse drug reactions (ADRs) reported. A statistically significant correlation was observed among comorbidities, number of prescribed medications, PIMs, and ADRs. Quality of life (QOL) of the elderly patients was negatively corelated with polypharmacy and female sex. Conclusion: A risk-benefit analysis of prescribed medications is part and parcel of prescribing, especially in elderly patients. In order to decrease further risks associated with inappropriate prescribing, there is need for indigenous guidelines and intensive training.

Adherence to COVID-19 protective behaviours in India from May to December 2020: evidence from a nationally representative longitudinal survey.

OBJECTIVES: Since 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. DESIGN: Nationally representative, panel-based, longitudinal study. SETTING: We 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. PARTICIPANTS: Respondents included 3719 adults from 1766 Indian households enrolled in the Harmonised Diagnostic Assessment of Dementia for the Longitudinal Ageing Study in India. ANALYSIS: We used ordinary least squares regression analysis to quantify time trends in protective behaviours. RESULTS: We 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. CONCLUSION: We 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.

Outcome of older adults at risk of frailty.

BACKGROUND: The integral part of the definition of frailty is the outcome associated with it. Older adults at risk of frailty are in the process of becoming frail. This study looked at the clinical characteristics and outcomes of older adults at risk of frailty. METHODOLOGY: The study population was selected from outpatient department of the geriatric medicine department in a tertiary care hospital. Older adults identified as at risk of frailty were assessed at baseline and then followed up after 1 year for the composite primary outcome of death, falls, hospitalization, and self-rated poor quality of life in the follow-up period. RESULTS: The study included 324 older adults who had completed 1-year follow up. Mean (SD) age was 74.49 (4.58) years, and males were 241 (74.15%). Frail and pre-frail at baseline among the study population were 31.17% and 61.11%, respectively. The primary outcome occurred in 43 (13.27%) patients. Poor baseline IADL was significantly associated with primary outcome at the end of 1 year. CONCLUSION: An unfavorable outcome in older adults at risk of frailty was significantly higher and independent of their baseline frailty status. Poor baseline IADL value may be considered as a predictor for primary outcome at 1 year of follow up.

Assessment of mental health issues among geriatric population during COVID19 pandemic, Indian perspective.

OBJECTIVES: Study was aimed to assess magnitude of mental health problems among geriatric population during COVID19 pandemic. METHODOLOGY: Study was a cross-sectional observational study, total of 106 participants (Age ≥60 years) of either gender included in study. Mental health variables depressive and anxiety were assessed using GDS and HAM-A. RESULTS: On GDS, 20(18.87%) patients had depressive symptoms and on HAM-A, 24(22.6%) patients were having anxiety symptoms. CONCLUSION: Study highlight that Geriatric population have significant mental health issues during COVID19 pandemic, it should not be overlooked. It's necessary to provide elderly psychological intervention measures to improve their wellbeing.

Clinical features and outcomes of COVID-19 in older adults: a systematic review and meta-analysis.

BACKGROUND: Few studies have focused on exploring the clinical characteristics and outcomes of COVID-19 in older patients. We conducted this systematic review and meta-analysis to have a better understanding of the clinical characteristics of older COVID-19 patients. METHODS: A systematic search of PubMed and Scopus was performed from December 2019 to May 3rd, 2020. Observational studies including older adults (age ≥ 60 years) with COVID-19 infection and reporting clinical characteristics or outcome were included. Primary outcome was assessing weighted pooled prevalence (WPP) of severity and outcomes. Secondary outcomes were clinical features including comorbidities and need of respiratory support. RESULT: Forty-six studies with 13,624 older patients were included. Severe infection was seen in 51% (95% CI- 36-65%, I2-95%) patients while 22% (95% CI- 16-28%, I2-88%) were critically ill. Overall, 11% (95% CI- 5-21%, I2-98%) patients died. The common comorbidities were hypertension (48, 95% CI- 36-60% I2-92%), diabetes mellitus (22, 95% CI- 13-32%, I2-86%) and cardiovascular disease (19, 95% CI - 11-28%, I2-85%). Common symptoms were fever (83, 95% CI- 66-97%, I2-91%), cough (60, 95% CI- 50-70%, I2-71%) and dyspnoea (42, 95% CI- 19-67%, I2-94%). Overall, 84% (95% CI- 60-100%, I2-81%) required oxygen support and 21% (95% CI- 0-49%, I2-91%) required mechanical ventilation. Majority of studies had medium to high risk of bias and overall quality of evidence was low for all outcomes. CONCLUSION: Approximately half of older patients with COVID-19 have severe infection, one in five are critically ill and one in ten die. More high-quality evidence is needed to study outcomes in this vulnerable patient population and factors affecting these outcomes.

Impact of physical activity on mitochondrial enzymes, muscle stem cell and anti-oxidant protein Sestrins in Sarcopenic mice.

INTRODUCTION: Sarcopenia is the loss of skeletal muscle mass and function. It is a major health issue in old age due to lack of understanding of the origin and molecular mechanism. Altered dietary pattern, sedentary lifestyle and physical inactivity have shown adverse effect of skeletal muscle function. Sedentary behaviour and low protein intake have been well associated with sarcopenia. Here, we aim to develop Sarcopenia mimicking murine model to observe the physiological and biochemical changes with physical activity intervention. We also intended to find the association of muscle stem cells and stress induced protein Sestrins in the developed sarcopenic model. METHODS: Male C57BL/6 mice were categorized into 4 groups: young-control (Y-Cntrl), aged-matched control (A-Cntrl), Sarcopenic-model (SAR-model) and Sarcopenic intervention group (SAR-INT) with physical exercises. SAR-model group was kept in a retrofitted confined cage for sedentary lifestyle and was fed with protein-restricted diet. Phenotypic assessment for body mass, grip strength and functional endurance was analysed to confirm the sarcopenic state. Mitochondrial enzymatic assessment, muscle stem cell (MuSCs) proliferation potential and protein quantification of Sestrins expression were performed by enzyme histochemistry, flow cytometry and surface plasmon resonance (SPR), respectively. SAR-model group was given 10 weeks physical activity intervention to assess the physiological and biochemical changes. RESULTS: Simultaneous implementation of physical inactivity by sedentary confinement and protein restricted diet led the animals to exhibit the features of sarcopenia. SAR-model group showed a decline of 8.6% (p < 0.0001) in the body weight assessment, 32% decline (p < 0.0001) in the grip strength, 28% increase in time elapsed (p < 0.0001) indicating decline in functional performance. Mitochondrial enzymes (ATPase, NADH-TR and SDH/COX) assessment exhibited low expression in SAR-model group. Ki67 positive muscle stem cell declines around 50% in the model group. SPR quantification of Sestrin 2 showed a decline of 14% which significantly improved to 28% upon physical activity intervention (p = 0.0025) in SAR-INT group. CONCLUSION: It can be summarized that the mouse model generated in the present study mimics the feature of human Sarcopenia. Physical activity intervention may improve the sarcopenic status via modulation of Sestrin 2 which can serve as potential molecule for therapeutic implication.

A novel approach to correlate the salivary exosomes and their protein cargo in the progression of cognitive impairment into Alzheimer's disease.

BACKGROUND: Cognition is the ability of a person to think, remember, and interconnect ideas from various dimensions to strive for solutions. Cognitive defects accompany all forms of dementia and the decline in cognition is a most feared aspect. Mild cognitive impairment is considered as a transitional phase and the progressive loss in cognition can finally lead to Alzheimer's disease. NEW METHOD: In this study, we demonstrated a novel method based on nanoparticle tracking analysis (NTA) technique to directly correlate salivary exosomes concentration with the progression of cognitive impairment (CI) in Alzheimer's disease (AD).This could open up the possibility for an early and cost-effective screening of Alzheimer's disease. RESULTS: Using our novel method, the total salivary exosomes concentration was measured by NTA technique, followed by validation of key exosomal cargo proteins through an automated western blot analyzer. We observed significant differences in salivary exosomes concentration among the groups of cognitively impaired and Alzheimer's disease patients (p = 0.0023) compared to the healthy control cohort. The method was validated through CD63 (exosomes surface marker) fluorescent antibody based quantification, which yielded a similar outcome (p = 0.0286). We further corroborated our findings with the expression level of oligomeric amyloid-beta, phosphorylated-tau protein from salivary exosomes. The Aß oligomer/fibril abundance (p = 0.0291), phospho-tau (p = 0.0325) and Aß protein abundance (p = 0.0198) was significantly higher in Alzheimer's and cognitively impaired patients in comparison to the healthy controls. COMPARISON WITH EXISTING METHOD(S): There are few molecular biomarkers available to differentiate between various stages of cognitive impairment. Moreover, the current methodologies utilizing the few biomarkers available are either invasive or expensive; also, for a patient with mild cognitive complains, it is impractical to use these as a screening tool. CONCLUSION: Our initial results indicate that the salivary exosomes concentration based on the nano-tracking technique has the potential to be used as a cost-effective screening method for early disease detection.

Hypertension and Cognitive Health Among Older Adults in India.

OBJECTIVES: To assess the prevalence of diagnosed and undiagnosed hypertension and their relationship to cognitive function in older adults in India. DESIGN: Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (LASI-DAD), an in-depth national study of late-life cognition and dementia. SETTING: Geriatric hospitals and respondents' homes across 14 states in India. PARTICIPANTS: N = 2,874 individuals aged 60 years and older from LASI-DAD. MEASUREMENTS: Hypertension was identified by self-report of physician diagnosis or measured blood pressure (BP) of 140/90 mmHg or higher. Undiagnosed hypertension was defined as hypertensive BP measurements, but no physician diagnosis. Controlled hypertension was defined as BP lower than 140/90 mmHg among those with a physician diagnosis. Total hypertension included both diagnosed and undiagnosed hypertension. A summary cognition score, derived from the sum of 18 cognitive tests administered in the LASI-DAD (range = 0-360) was used to assess cognitive function. RESULTS: Total hypertension prevalence was 63.2% (41.5% diagnosed and 21.6% undiagnosed). Among those with hypertension, 34.5% were undiagnosed, 34.2% were diagnosed but uncontrolled, and 31.3% were diagnosed and controlled. Neither diagnosed nor undiagnosed hypertension was related to cognitive function in fully adjusted models. Older age, female sex, less education, being widowed, rural residence, residing in the north or central regions, being in a scheduled caste or tribe, low consumption, being underweight, and history of stroke were all independently associated with worse cognitive test performance. CONCLUSION: Two-thirds of older Indian adults had hypertension, with the majority being undiagnosed or diagnosed but not adequately controlled. Hypertension was not independently associated with cognitive function, whereas sociodemographic factors were independently related to cognitive function. J Am Geriatr Soc 68:S29-S35, 2020.