Plasma Inflammatory Biomarkers and Anorexia of Ageing among Community-Dwelling Older Adults: An Exploratory Analysis of the MAPT Study.

Anorexia of aging and biological aging might share physiological underpinnings. The aim of this secondary analysis was to investigate the associations between circulating inflammation-related markers and anorexia of aging in community-dwelling older adults. C-reactive protein (CRP), tumor necrosis factor receptor-1 (TNFR-1), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and growth/differentiation factor-15 (GDF-15) were measured in plasma. Anorexia of aging was defined by the response "severe/moderate decrease in food intake" to the first item of the Mini-Nutritional Assessment. We included 463 subjects (median age=74y, IQR=71-78; 63.1% women). 33 subjects (7.1%) presented with anorexia at baseline, whereas 25 out of 363 (6.9%) developed it along 1-year follow-up. We found that TNFR1 (OR=1.74, 95%CI=1.27-2.39) and GDF-15 (OR=1.38, 95%CI=1.01-1.89) were associated with a significant increase in the odds of presenting with anorexia of aging cross-sectionally. No further significant associations were found. Biological aging mechanisms might be involved in the pathogenesis of anorexia of aging.

Biomarkers of Age-Related Frailty and Frailty Related to Diseases: An Exploratory, Cross-Sectional Analysis from the MAPT Study.

BACKGROUND: Frailty may in most cases result from two main causes: the aging process (age-related frailty) and diseases (evolving chronic conditions or acute medical illnesses - disease-related frailty). The biological determinants characterizing these two main causes of frailty may be different. OBJECTIVES: The aim of this study is to compare the biological and neuroimaging profile of people without frailty, those with age-related frailty, and subjects with disease-related frailty in community-dwelling older adults. MATERIAL AND METHODS: We performed a secondary, cross-sectional analysis from the Multidomain Alzheimer Preventive Trial (MAPT). We included 1199 subjects without frailty throughout the 5-year follow-up, 82 subjects with incident age-related frailty, and 53 with incident disease-related frailty. Available blood biomarkers involved nutritional (eg, vitamin D, omega-3 fatty acids), inflammatory-related (IL-6, TNFR1, GDF15), neurodegenerative (eg, beta-amyloid, neurofilament light chain) and neuroimaging markers (MRI, Amyloid-PET). RESULTS: Although not statistically significant, the results of the unadjusted model showed increasing gradients for inflammatory markers (GDF15, TNFR1) and decreasing gradients for nutritional and neuroimaging markers (omega 3 index, hippocampal volume) from age-related frailty participants to individuals with disease-related frailty. Considering the linear models we observed higher GDF15 values in disease-related frailty group compared to age-related frailty individuals [ß = 242.8 (49.5, 436.2)]. We did not find any significant difference between subjects without frailty and those with age-related frailty. Subjects with disease-related frailty compared to subjects without frailty had lower values of DHA [ß = -2.42 (-4.76, -0.08)], Omega 3 Index [ß = -0.50 (-0.95, -0.06)] and hippocampal volume [ß = -0.22 (-0.42,-0.02)]. They also had higher values of GDF15 [ß = 246.1 (88.9, 403.4)] and TNFR1 [ß = 157.5 (7.8, 307.2)]. CONCLUSION: Age-related frailty and disease-related frailty may represent different degrees of frailty severity on a biological level. Further research is needed to identify biomarkers potentially able to distinguish these classifications of frailty.

A Web-Based Multidomain Lifestyle Intervention for Older Adults: The eMIND Randomized Controlled Trial.

Importance/Objective: To describe the feasibility and acceptability of a 6-month web-based multidomain lifestyle training intervention for community-dwelling older people and to test the effects of the intervention on both function- and lifestyle-related outcomes. DESIGN: 6-month, parallel-group, randomized controlled trial (RCT). SETTING: Toulouse area, South-West, France. PARTICIPANTS: Community-dwelling men and women, ≥ 65 years-old, presenting subjective memory complaint, without dementia. INTERVENTION: The web-based multidomain intervention group (MIG) received a tablet to access the multidomain platform and a wrist-worn accelerometer measuring step counts; the control group (CG) received only the wrist-worn accelerometer. The multidomain platform was composed of nutritional advices, personalized exercise training, and cognitive training. Main outcomes and measures: Feasibility, defined as the proportion of people connecting to ≥75% of the prescribed sessions, and acceptability, investigated through content analysis from recorded semi-structured interviews. Secondary outcomes included clinical (eg, cognitive function, mobility, health-related quality of life (HRQOL)) and lifestyle (eg, step count, food intake) measurements. RESULTS: Among the 120 subjects (74.2 ±5.6 years-old; 57.5% women), 109 completed the study (n=54, MIG; n=55, CG). 58 MIG subjects connected to the multidomain platform at least once; among them, adherers of ≥75% of sessions varied across multidomain components: 37 people (63.8% of 58 participants) for cognitive training, 35 (60.3%) for nutrition, and three (5.2%) for exercise; these three persons adhered to all multidomain components. Participants considered study procedures and multidomain content in a positive way; the most cited weaknesses were related to exercise: too easy, repetitive, and slow progression. Compared to controls, the intervention had a positive effect on HRQOL; no significant effects were observed across the other clinical and lifestyle outcomes. CONCLUSIONS AND RELEVANCE: Providing multidomain lifestyle training through a web-platform is feasible and well-accepted, but the training should be challenging enough and adequately progress according to participants' capabilities to increase adherence. Recommendations for a larger on-line multidomain lifestyle training RCT are provided.

The INSPIRE Bio-Resource Research Platform for Healthy Aging and Geroscience: Focus on the Human Translational Research Cohort (The INSPIRE-T Cohort).

BACKGROUND: The Geroscience field focuses on the core biological mechanisms of aging, which are involved in the onset of age-related diseases, as well as declines in intrinsic capacity (IC) (body functions) leading to dependency. A better understanding on how to measure the true age of an individual or biological aging is an essential step that may lead to the definition of putative markers capable of predicting healthy aging. OBJECTIVES: The main objective of the INStitute for Prevention healthy agIng and medicine Rejuvenative (INSPIRE) Platform initiative is to build a program for Geroscience and healthy aging research going from animal models to humans and the health care system. The specific aim of the INSPIRE human translational cohort (INSPIRE-T cohort) is to gather clinical, digital and imaging data, and perform relevant and extensive biobanking to allow basic and translational research on humans. METHODS: The INSPIRE-T cohort consists in a population study comprising 1000 individuals in Toulouse and surrounding areas (France) of different ages (20 years or over - no upper limit for age) and functional capacity levels (from robustness to frailty, and even dependency) with follow-up over 10 years. Diversified data are collected annually in research facilities or at home according to standardized procedures. Between two annual visits, IC domains are monitored every 4-month by using the ICOPE Monitor app developed in collaboration with WHO. Once IC decline is confirmed, participants will have a clinical assessment and blood sampling to investigate markers of aging at the time IC declines are detected. Biospecimens include blood, urine, saliva, and dental plaque that are collected from all subjects at baseline and then, annually. Nasopharyngeal swabs and cutaneous surface samples are collected in a large subgroup of subjects every two years. Feces, hair bulb and skin biopsy are collected optionally at the baseline visit and will be performed again during the longitudinal follow up. EXPECTED RESULTS: Recruitment started on October 2019 and is expected to last for two years. Bio-resources collected and explored in the INSPIRE-T cohort will be available for academic and industry partners aiming to identify robust (set of) markers of aging, age-related diseases and IC evolution that could be pharmacologically or non-pharmacologically targetable. The INSPIRE-T will also aim to develop an integrative approach to explore the use of innovative technologies and a new, function and person-centered health care pathway that will promote a healthy aging.

A web-based multidomain lifestyle intervention with connected devices for older adults: research protocol of the eMIND pilot randomized controlled trial.

BACKGROUND: Multidomain interventions composed of nutritional counseling, exercise and cognitive trainings have shown encouraging results as effective preventive strategies delaying age-related declines. However, these interventions are time- and resource-consuming. The use of Information and Communication Technologies (ICT) might facilitate the translation from research into real-world practice and reach a massive number of people. AIM: This article describes the protocol of the eMIND study, a randomized controlled trial (RCT) using a web-based multidomain intervention for older adults. METHODS: One hundred and twenty older adults (≥ 65 years), with a spontaneous memory complaint, will be randomly assigned to a six-month web-based multidomain (nutritional counseling, physical and cognitive trainings) intervention group with a connected accelerometer (number of steps, energy expenditure), or to a control group with access to general information on healthy aging plus the accelerometer, but no access to the multidomain intervention. The main outcome is the feasibility/acceptability of the web-based intervention. Secondary clinical outcomes include: cognitive functions, physical performance, nutritional status and cost-effectiveness. RESULTS: We expect a high amount of adherers (ie, > 75% compliance to the protocol) to reflect the feasibility. Acceptability, assessed through interviews, should allow us to understand motivators and barriers to this ICT intervention. We also expect to provide data on its effects on various clinical outcomes and efficiency. CONCLUSION AND DISCUSSION: The eMIND study will provide crucial information to help developing a future and larger web-based multidomain lifestyle RCT, which should facilitate the translation of this ICT intervention from the research world into real-life clinical practice for the healthcare of older adults.

Validation of the Mini Nutritional Assessment-Short Form in a Population of Frail Elders without Disability. Analysis of the Toulouse Frailty Platform Population in 2013.

OBJECTIVE: To assess the validity of the Mini Nutritional Assessment-Short Form (MNA-SF) in elderly patients from the Toulouse Frailty Platform. PARTICIPANTS: Overall, 267 patients aged 65 and over, without severe cognitive impairment (i.e. Mini Mental Status Examination > 20 and CDR<1), no physical disability (i.e. Activities of Daily Living ≥ 5) and no active cancer history (over the past 12 months) were included in 2013. MEASUREMENTS: Receiver operating characteristic (ROC) analyses were used to assess the predictive validity of the French version of the MNA-SF for good nutritional status (defined as a full MNA score≥24/30). Analyses were conducted in the overall sample and then in subgroups of frail and pre-frail subjects according to the frailty phenotype. Optimal cut-off points were determined to obtain the best sensitivity/specificity ratio and the highest number of correctly classified subjects. RESULTS: Among 267 patients, mean age=81.5±5.8; women=67.0%; 138 (51.7%) were frail, 98 (36.7%) were pre-frail and 31 (11.6%) were robust. Given their MNA-SF scores, 201 (75.3%) had a good nutritional status, 61 (22.8%) were at risk of malnutrition and 5 (1.9%) were malnourished. In the overall sample, but also in subgroups of pre-frail or frail elders, the areas under ROC curves were 0.954, 0.948 and 0.958 respectively. The 11 points cut-off provided the best correct classification ratio (91.4%); sensitivity=94.0%, specificity=83.3%. CONCLUSION: The MNA-SF appeared to be a validated and effective tool for malnutrition screening in frail elders. Implementing this tool in clinical routine should contribute to improving the screening of malnourished frail individuals.

Flavonoids and arterial stiffness: promising perspectives.

BACKGROUND AND AIMS: Flavonoids are a group of polyphenol compounds, ubiquitously found in plants. Great emphasis has been given to their possible benefits for cardiovascular health. These beneficial effects may be mediated by a specific action on arterial walls. Arterial stiffness is a marker of vascular aging, increasingly used in the clinical setting and assessed by pulse wave velocity. It has shown to be a robust predictor of cardiovascular events and mortality. This review aims at providing a comprehensive evaluation of available intervention and observational studies examining the relationship between flavonoid consumption and arterial stiffness. DATA SYNTHESIS: A Medline(®) literature search was performed using the keywords "arterial stiffness" and "flavonoids". As a result, 2 cross-sectional and 16 intervention studies assessing the relationship between flavonoids intake and arterial stiffness were retained. Four intervention trials reported a significant decrease of arterial stiffness after a flavonoid-based intervention, independently from blood pressure changes. The two observational studies reported significant associations between a higher flavonoid consumption and a lower arterial stiffness. In this review, isoflavones, anthocyanins and to a lesser extent cocoa flavan-3-ols appeared to be the more efficient to improve vascular function. CONCLUSIONS: Despite their heterogeneity, preliminary data seem to support an improvement of the arterial stiffness related to flavonoid intake. However, further research on absorption and dose-response effects of the specific flavonoid subclasses on arterial structure is warranted.

Prevention of progression to dementia in the elderly: rationale and proposal for a health-promoting memory consultation (an IANA Task Force).

Alzheimer's disease (AD) is the most frequent form of dementia and according to the most recent estimation it affects nearly 27 million people in the world. The onset of the disease is generally insidious. It is becoming increasingly evident that the underlying pathophysiological mechanisms are active long before the appearance of the clinical symptoms of the disease. In the current context, it is important to develop strategies to delay the onset of cognitive decline. Delaying the onset by 5 years would reduce the prevalence by half at term, and a delay of 10 years would reduce it by three-quarters. The effectiveness of currently suggested preventive approaches remains to be confirmed, but certain strategies could be applied straight away to at-risk subjects. We propose that a health-promoting memory consultation should be set up for elderly persons who have attended a specialized memory consultation and in whom the diagnosis of dementia and of AD in particular, has not been established by standardized tools. Through this consultation, they would be offered full multidimensional investigation of all aspects of their health status, follow-up could be organized, general practitioners in private practice could be made more conscious of this population and the elderly could be made more aware of the risk factors to which they are exposed. The development of an information policy for the elderly would meet a present need. In our reflection, we must take into account the question of how to give this preventive consultation its due place in the healthcare pathway of the elderly person in order to ensure coordinated follow-up with all the other health professionals involved. The principle of the health-promoting memory consultation is undergoing validation in a large French multicentre preventive trial in 1200 frail elderly persons aged 70 years followed for three years, the Multidomain Alzheimer Preventive Trial (MAPT).

A nutritional education program could prevent weight loss and slow cognitive decline in Alzheimer's disease.

BACKGROUND: Weight loss is a common problem in patients with Alzheimer's Disease (AD). It is a predictive factor of mortality and it decreases patients' and caregivers' quality of life. OBJECTIVE: To determine if a nutritional education program can prevent weight loss in AD patients. SUBJECTS: 151 AD patients and their caregivers were enrolled to follow the intervention and 74 AD patients and their caregivers constituted a control group. METHOD: Caregivers in the intervention group followed 9 nutritional sessions of one hour each, over one year. Caregivers in the control group didn't follow any sessions but were offered advice provided in a normal follow-up. Patients weight, nutritional state, cognitive function, autonomy, mood, behaviour disorders at baseline and at 6- and 12-month follow-up. Caregivers burden, nutritional and AD knowledge at the baseline and at the 12-month follow-up. RESULTS: During the year follow-up, the mean weight increased in the intervention group (0.7+/-3.6 kg) whereas it decreased in the control group (-0.7+/-5.4 kg) (p<0.05). The nutritional status (MNA) was maintained in the intervention group (0.3+/-2.6) whereas it decreased significantly in the control group (-1.0+/-3.4) (p<0.005). After adjustment for baseline differences between the two groups (caregiver age, nutritional state, eating behaviour disorders, depression), the weight change between the two groups was not significant (0.6+/-0.4 kg vs. -0.6+/-0. 6 kg respectively in intervention group and control group). However, the percentage of patients with significant weight loss is decreased. The MMSE change became significant between the two groups: -2.3+/-0.3 vs. -3.4+/-0.4 respectively in intervention group and control group (p<0.05). CONCLUSIONS: These results suggest that a nutritional educational program intended for caregivers of AD patients could have a positive effect on patients weight and cognitive function.

Alzheimer disease: protective factors.

Approximately 6-8% of all persons aged >65 y have Alzheimer disease and the prevalence of the disease is increasing. Any intervention strategy aimed at decreasing risks or delaying the onset of the disease will therefore have a substantial effect on health care costs. Nutrition seems to be one of the factors that may play a protective role in Alzheimer disease. Many studies suggest that oxidative stress and the accumulation of free radicals are involved in the pathophysiology of the disease. Several studies have shown the existence of a correlation between cognitive skills and the serum concentrations of folate, vitamin B-12, vitamin B-6, and, more recently, homocysteine. However, nutritional factors have to be studied not alone but with the other factors related to Alzheimer disease: genetics, estrogen, antiinflammatory drug use, and socioeconomic variables. The objective of this article was to review recent studies in this field.