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.

Old age-associated enrichment of peripheral T regulatory cells and altered redox status in pulmonary tuberculosis patients.

Aging influences the susceptibility and prognosis to various infectious diseases including tuberculosis (TB). Despite the impairment of T-cell function and immunity in older individuals, the mechanism for the higher incidence of TB in the elderly remains largely unknown. Here, we evaluated the age-associated immune alterations, particularly in effector and Treg responses in pulmonary TB patients. We also evaluated the impact of redox status and its modulation with N-acetyl-cysteine (NAC) in elderly TB. Higher frequency of Treg cells and reduced IFN-γ positive T cells were observed among older TB patients. The elevated number of Treg cells correlated tightly with bacillary load (i.e. disease severity); which declined significantly in response to successful anti-tubercular treatment. We could rescue Myobacterium tuberculosis-specific effector T cell (Th1) responses through various in vitro approaches, for example, Treg cell depletion and co-culture experiments, blocking experiments using antibodies against IL-10, TGF-ß, and programmed death-1 (PD-1) as well as NAC supplementation. We report old age-associated enrichment of Treg cells and suppression of M. tuberculosis-specific effector T (Th1) cell immune responses. Monitoring these immune imbalances in older patients may assist in immune potentiation through selectively targeting Treg cells and/or optimizing redox status by NAC supplementation.

Sestrin2 as Serum Protein Marker and Potential Therapeutic Target for Parkinson's Disease.

Sestrin2 (Sesn2) appears to mediate neuroprotection against Parkinson's disease (PD)-associated pathophysiology, however, the mechanism is unknown. This pilot study examines serum Sesn2 level in PD patients and older adult control and also interrogates the rescue effect of Syzygium aromaticum extract on the neurotoxicity by paraquat in neuroblastoma cells. The blood sample was collected from 36 PD patients and 54 older adult control and concentration of serum Sesn2 was measured by surface plasmon resonance and western blot. A significantly elevated level of Sesn2 (p < .0001) was observed in sera of PD group (15.96 ± 2.428 ng/µL) than the control (13.65 ± 2.125 ng/µL) which was further confirmed by western blotting. The receiver operating characteristic (ROC) curve (0.76) determined the threshold value of ≥14.58 ng/µL for differentiating PD from control. The S aromaticum extract exhibited the rescue effect from paraquat induced toxicity in SH-SY5Y cells. Further, these cells showed dose-dependent downregulation of p53, Sesn2, and phosphorylated-AMPK with concomitant increase in phosphorylated-p70S6K level than paraquat-treated cells. The differential level of Sesn2 in study subjects proposes its utility as one of the potential serum markers in PD. The ethanolic extract of S aromaticum may serve as a novel platform for management of PD-associated neurotoxicity.

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.