Intrinsic Capacity as a Determinant of Physical Resilience in Older Adults.

The traditional disease-oriented model of healthcare is inadequate to address the needs of the older population. Greater attention should be given to strategies that promote healthy aging. Recently proposed constructs of intrinsic capacity (IC) and physical resilience (PR) hold great potential to reshape geriatric medicine and aging research. These constructs accentuate the positive health attributes of older people in contrast to the popular frailty construct that is centered on functional deficits. IC was introduced by the World Health Organization (WHO) as a composite of all the physical and mental capacities. WHO has emphasized enhancement of IC throughout the life course so as to maintain functional ability in old age. PR, recently highlighted by the National Institute on Aging, is the ability to successfully cope with stressors. High levels of resilience can result in desirable clinical and functional outcomes after stressors. Therefore, it is important to understand the underlying physiology of PR and the risk factors contributing to diminished PR. The main goal of this article is to explore the potential relationship between IC and PR. Based on a classical theory of aging, we postulate that IC is a determinant of PR and is also a high-level integrative measure of physiologic reserve which is the fundamental factor underlying one's ability to withstand stressors. A major implication of our postulates is that even though IC is only one of the many determinants of PR, it could serve as an important intervenable target for enhancing resilience in older adults.

Apolipoprotein E Polymorphism and Frailty: Apolipoprotein ε4 Allele Is Associated with Fatigue but Not Frailty Syndrome in a Community-Dwelling Older Population Cohort.

OBJECTIVE: Frailty is known to be influenced by genetics, however, little evidence on the association of Apolipoprotein E (ApoE) genotype and frailty exists which we aim to investigate. DESIGN: This study is a cross-sectional analysis from a prospective longitudinal study cohort. SETTING AND PARTICIPANTS: Community-dwelling individuals aged 55 years and older from Beijing region in China. MEASUREMENTS: A total of 3,569 older adults with a mean age of 75.06(±6.79) years were included. We investigated the association between ApoE polymorphism and frailty syndrome using the frailty index (FI) and frailty phenotype (including association with individual components of the frailty phenotype). Logistic regressions were performed to investigate the relation between ApoE variants and frailty. RESULTS: There was no significant association between ApoE variants and frailty as assessed by the FI. In the age and sex-adjusted model, compared to the ApoE e3/e3 carriers ApoE e4 carriers had almost 1.5 times higher odds of being frail as assessed by the frailty phenotype. However, the significance was lost on the model with adjustment for cognitive impairment. Compared to the ApoE e3/e3 carriers ApoE e4 carriers had almost two times higher odds of fatigue. ApoE e4 heterozygotes had higher odds of fatigue compared to ApoE e4 non-carriers. No significant association was found between ApoE variants and other components of frailty phenotype. CONCLUSIONS: Our findings do not support an association between ApoE genotype and frailty irrespective of the frailty assessment tools. Fatigue in older adults is the only component of frailty phenotype influenced by ApoE genotype.

Frailty in China: From Research to Practice.

Although geriatric research in general has increased in recent years, there is no effective treatment for frailty. Among older adults, those with frailty have an increased risk of falls, disability, and death. The population of older adults has increased rapidly in China, and resulting in an increased demand for medical care services for older adults, including those with frailty. However, much of the research on frailty has been conducted in Europe and the United States, and European and American standards for frailty are not always applicable to Chinese individuals. Clinicians and researchers in China have shown increasing interest in frailty in recent years. Here, we reviewed the current state of frailty research in China.

Plasma N-Terminal Pro-B-Type Natriuretic Peptide Is Associated with Intrinsic Capacity Decline in an Older Population.

OBJECTIVES: To determine the association between plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) and intrinsic capacity in an older population. METHOD: We recruited 283 participants aged 60-97 years (mean 77.42±4.08 years). Intrinsic capacity was assessed with the World Health Organization Integrated Care for Older People (ICOPE) screening tool including six domains: cognition, locomotion, vitality, hearing, vision, and psychology. Multimorbidity, polypharmacy, gait speed, physical activity, lifestyles, and chronic inflammation were assessed. We used multivariate logistic regression and the Spearman's correlation to assess the association between plasma NT-proBNP and intrinsic capacity. RESULTS: The average intrinsic capacity score was 4.53±1.34. The percentage of decreased intrinsic capacity was 75.3%. Participants with decreased intrinsic capacity were older, with more cardiovascular and cerebrovascular diseases and polypharmacy, and had lower gait speed and higher C-reactive protein. Plasma NT-proBNP was significantly higher in the decreased intrinsic capacity group (128.0[56.8-280.8] pg/mL vs. 72.6[39.7-120.0] pg/mL, p<0.001). Multivariate logistic regression analysis revealed that NT-proBNP was the only independent risk factor for decreased intrinsic capacity among multiple covariates (odds ratio=1.005, p=0.038). Elevated NT-proBNP levels were associated with abnormal locomotion, hearing, vision, and psychology domains. Additionally, NT-proBNP levels were inversely correlated with the intrinsic capacity score adjusted for both age and coronary artery disease (r=-0.371, p< 0.001). CONCLUSION: Elevated NT-proBNP levels were associated with decreased intrinsic capacity in older persons, independent of age, multimorbidity, polypharmacy, and chronic inflammation. Further longitudinal studies are required to explore the predictive role of NT-proBNP on declines in intrinsic capacity.

A Frailty Screening Questionnaire (FSQ) to Rapidly Predict Negative Health Outcomes of Older Adults in Emergency Care Settings.

BACKGROUND: Frailty, at the core of geriatric medicine, is an important concept underpinning health problems but the rapid and valid measurement of frailty for older adults in the Emergency Department (ED) is lacking in China. The Frailty Screening Questionnaire (FSQ), has been shown to be a simple, rapid and practical tool to identify frailty in both community and inpatients settings, yet its utility in acute care settings is not well understood. OBJECTIVE: To determine whether FSQ is useful to identify frailty and predict adverse outcomes in an emergency care setting. DESIGN AND PARTICIPANTS: This prospective study included 350 adults aged 60 and over and admitted to the ED. MEASUREMENTS: The FSQ questionnaire which assessed self-reported slowness, weakness, inactivity, exhaustion, and weight loss was used to rapidly recognize frailty. FRAIL, Clinical frailty score (CFS), activities of daily living (ADL) and nutrition risk screening 2002 were also assessed. Outcome measures included all-cause 28-day mortality, ADL dependency, mechanical ventilation, length of hospital stay, and ICU readmissions 30 and 90 days after discharge. Cox proportional hazard model was used for survival comparison. RESULTS: The prevalence of FSQ frailty and prefrailty in older adults were 44.6% and 30.9% respectively in the emergency setting. FSQ frailty was associated with increasing age, chronic diseases, malnutrition risk, poor physical function and worse outcomes indicated by higher 28-d mortality, ADL dependency, mechanical ventilation, length of hospital stay, and ICU readmissions after discharge. The Kappa coefficient between the FSQ and FRAIL was 0.552. FSQ score was negatively correlated with grip strength and positively correlated with Barthel index, length of hospital stay and CFS score. Cox regression adjusted by epidemiological variables and chronic diseases showed FSQ and all components predicted mortality except weight loss. CONCLUSION: The FSQ is a rapid and useful tool to screen frailty and an effective tool to predict mortality in busy emergency settings.

Report from the First Clinical Trials on Alzheimer's Disease (CTAD) Asia-China 2018 : Bringing together Global Leaders.

Population of older adults in Asia, and particularly in China is increasing rapidly. Older population are at increased risk of Alzheimer's disease (AD) and other dementias. Soon, the Chinese population with AD will represent almost half of the world's AD population. There is a desperate need of disease modifying therapies to delay or slow the progression of AD, to tackle this emerging healthcare emergency. In this context, the first CTAD Asia-China conference was held in China to bring together Western and Asian leaders in AD. This meeting focused largely on how to develop successful trials in China, utilizing past experiences from the West.

Prevention of Disability in the Frail Chinese Older Population.

As aging is becoming a global phenomenon, the burden of population aging is increasing rapidly, and is soon expected to be the highest in low-and middle-income countries. China represents the world's largest population, and will face the largest number of older individuals, while the economy still remains developing. There is an urgent need to address the negative consequences of aging such as disability, that creates a myriad of challenges, including financial burden to the economy. In order to achieve successful aging-i.e., aging without being frail or disabled, the traditional healthcare model based on a disease-centered approach is not enough, but require a more holistic course. Here, we briefly outline the current scenario of aging and disability in the Chinese older population, its impact and challenges. We strongly believe that public health initiatives centered on frailty, a clinically distinguishable state of extreme vulnerability in older adults, could be the most relevant approach to meet the current needs of the aging population. Such initiatives are immediately needed to reshape the existing model of geriatric healthcare, to promote healthy aging and to reduce the burden of disability in the Chinese population.

Vitamin D, homocysteine and n-3PUFA status according to physical and cognitive functions in older adults with subjective memory complaint: Results from cross-sectional study of the MAPT trial.

OBJECTIVE: The aim of this study was to investigate the nutritional markers (Vitamin D, homocysteine, n-3PUFA) status of older subjects aged 70 years and older with subjective memory complaint, according to their physical and cognitive function. MAIN OUTCOME MEASURES: This study is a secondary analysis of the MAPT study. Subjects were classified into four groups: 1) Physical limitation with cognitive impairment (PLCI), 2) cognitive impairment (CI), 3) physical limitation (PL) and 4) no physical or cognitive deficits (NPCD). Baseline nutritional characteristics of the four groups according to Vitamin D (n = 732), Omega-3 polyunsaturated fatty acid (n-3PUFA) (n = 1537) and plasma total homocysteine (tHcy) (n = 729) status were investigated. Analysis was performed taking continuous and dichotomized value for Vitamin D insufficiency ([25(OH)D] < 30 ng/ml, high homocysteine level (tHcy ≥ 15 µmol/L) and low n-3PUFA (DHA + EPA ≤ 4.82%) nutritional markers for clinical relevance. RESULTS: PLCI group showed the lowest mean level of Vitamin D and highest level tHcy compared to the other groups. In multivariate analysis, taking continuous nutritional markers, only high Vitamin D was associated with reduced likelihood of PLCI (OR 0.97, 95% CI (0.95 to 0.99) P = 0.011). While taking the dichotomized values the group with low levels of n-3PUFA showed higher likelihood of PL only (OR 1.55, 95% CI (1.12 to 2.15), P = 0.009). Furthermore, our sensitivity analysis for Vitamin D with cut-off [25(OH)D] < 20 ng/ml,(i.e., Vitamin D deficiency), showed more likelihood of PL (OR 1.62, 95% CI (1.01 to 2.60) P = 0.046), CI (OR 1.90, 95% CI (1.16 to 3.10) P = 0.010), and highest likelihood of PLCI (OR 1.99, 95% CI (1.21 to 3.28) P = 0.006). CONCLUSION: In older adults with subjective memory complaints, Vitamin D deficiency status may present higher likelihood of functional deficits, including coexisting or separate physical and cognitive decline. While older adults with low level of n-3PUFA were more likely to demonstrate physical decline only.

Trajectory of the MAPT-PACC-Preclinical Alzheimer Cognitive Composite in the Placebo Group of a Randomized Control Trial: Results from the MAPT Study: Lessons for Further Trials.

Defining the primary cognitive endpoint is a major decision for Alzheimer's disease preventive trials. As an example for further trials we present in detail the three-year cognitive decline in the placebo group of MAPT trial, a randomized controlled trial (RCT) using a cognitive composite score (MAPT-PACC). Participants were dementia-free adults 70 years or older, with subjective memory complaints. Our findings as expected showed subjects with older age (>75), higher beta amyloid brain deposition, APOE-ε4 allele carriers, with low RBC DHA+EPA levels and higher CDR level are at higher risk of cognitive decline. The data presented in this paper can be useful for future preventive trials to choose the primary cognitive end point, assess the clinical relevance of cognitive changes and perform sample size calculation for several targeted population eg. ApoE4, amyloid +, oldest old, lower n3-PUFA. We believe that the trial group with CDR 0.5, without being selected by a memory test endpoint is a good target population for AD preventive trials.