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.

Frequency of Conditions Associated with Declines in Intrinsic Capacity According to a Screening Tool in the Context of Integrated Care for Older People.

BACKGROUND: The screening tool of the Integrated Care for Older People (ICOPE Step 1), designed to detect declines in the domains of intrinsic capacity, has been incipiently investigated in older adult populations. OBJECTIVES: To retrospectively estimate the frequency of priority conditions associated with declines in intrinsic capacity according to an adaptation of the screening tool ICOPE Step 1 among participants of the Multidomain Alzheimer Preventive Trial (MAPT). DESIGN: A cross-sectional retrospective analysis from the baseline assessment of the MAPT. SETTING: The data was gathered during a preventive consultation for cardiovascular risk factors in memory clinics in France. PARTICIPANTS: Seven hundred fifty-nine older adults aged 70-89 years with memory complaints, allocated to the multidomain groups of the MAPT study. MEASUREMENTS: Five domains of intrinsic capacity (cognition, locomotion, nutrition, sensorial, and psychological) were assessed using a screening tool similar to the ICOPE Step 1 (MAPT Step 1). The frequency of six conditions associated with declines in intrinsic capacity (cognitive decline, limited mobility, malnutrition, visual impairment, hearing loss, and depressive symptoms) was obtained for older adults with memory complaints participating in the MAPT study. RESULTS: Overall, 89.3% of the participants had one or more conditions associated with declines in intrinsic capacity. The overall frequency of each condition was: 52.2% for cognitive decline, 20.2% for limited mobility, 6.6% for malnutrition, 18.1% for visual impairment, 56.2% for hearing loss, and 39% for depressive symptoms. CONCLUSION: After being screened with an adaptation of the ICOPE step 1 (MAPT step 1) tool, 9/10 older adults had one or more conditions associated with declines in intrinsic capacity. The relative frequency differs across conditions and could probably be lower in a population without memory complaints. The frequency of screened conditions associated with declines in IC highlights how relevant it is to develop function-centered care modalities to promote healthy aging.

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.

No Difference in the Phenotypic Expression of Frailty among Elderly Patients Recently Diagnosed with Cancer Vs Cancer Free Patients.

OBJECTIVES: To examine frailty determinants differences in patients with a recent diagnosis of cancer compared to non-cancer patients among older adult. Revealing those differences will allow us to individualize the exact frailty management in those patients diagnosed with cancer. DESIGN: This is an observational cross-sectional, monocentric study. SETTING: Patients were evaluated at the Geriatric Frailty Clinic (GFC), in the Toulouse University Hospital, France, between October 2011 and February 2016. PARTICIPANTS: 1996 patients aged 65 and older were included (1578 patients without cancer and 418 patients with solid and hematological cancer recently diagnosed). MEASUREMENTS: Frailty was established according to the frailty phenotype. The frailty phenotype measures five components of frailty: weight loss, exhaustion, low physical activity, weakness and slow gait. Frailty phenotype was categorized as robust, pre-frail and frail. RESULTS: In a multinomial logistic regression, cancer, compared to the non-cancer group, is not associated with an increased likelihood of being classified as pre frail (RRR 0.9, 95% CI [0.5 ; 1.6 ], p 0.9) or frail (RRR 1.2, 95% CI [0.7 ; 2.0], p 0.4) rather than robust. When considering each Fried criterion, a significant higher odd of weight loss was observed in older patients with cancer compared to the non-cancer patients (OR 2.3, 95% CI [1.8; 3.0], p <0.001) but no statistically significant differences was found among the four other Fried criteria. Sensitivity analysis on the frailty index showed that cancer was not associated with a higher FI score compared to non-cancer (ß 0.002, 95%CI [-0.009; 0.01], p 0.6). CONCLUSION: In this real-life study evaluating elderly patients with and without cancer, we didn't confirm our hypothesis, in fact we found that cancer was not associated with frailty severity using both a phenotypic model and a deficit accumulation approach. Cancer may contribute, at least additively, to the development of frailty, like any other comorbidity, rather than a global underlying condition of vulnerability.

Associations Between Multidomain Lifestyle Interventions and Intrinsic Capacity Domains During Aging: A Narrative Review.

Background: Recently, the World Health Organization defined five domains of intrinsic capacity (IC), composed of physical and mental capacities linked to body functions, and that contribute to healthy aging: locomotion, cognition, psychological, vitality and sensorial. In the past decade, studies investigating the effects of concomitant lifestyle interventions (also called multidomain interventions) on one or several IC domains have been developed. The aim of this study is to synthetize the scientific literature about the associations between multidomain lifestyle interventions and IC domains. Methods: We conducted a narrative review of randomized controlled trials examining the effects of multidomain lifestyle interventions on at least one IC domain among older people. Multidomain intervention was defined as the presence of at least two of the following lifestyle interventions: physical activity/exercise, nutrition, cognitive stimulation, and management of cardiovascular risk factors (eg, smoking, alcohol consumption). Results: Multidomain interventions were associated with improvements on locomotion (as measured by performance-based tests of lower-limb function) and vitality (as measured by handgrip strength); benefits on cognitive function were also found, in particular among populations at increased risk of dementia and when operationalizing strong multidomain interventions (eg, using regular exercise training instead of physical activity advices). No study investigated the effects of multidomain lifestyle interventions on the sensorial domain (hearing and/or vision). The modalities composing the multidomain interventions and intervention length, as well as study population, substantially varied across studies; the most common combination of interventions was physical activity- and nutritional-related interventions. Conclusion: Available evidence is still limited, but literature suggests a positive effect of multidomain lifestyle interventions on IC domains, in particular locomotion. Further studies are still needed on this topic, in particular, studies exploring the effects of multidomain lifestyle interventions on the sensorial domain, as well as on a composite measurement of all IC domains.

Physical Activity and Changes in White Matter Hyperintensities over Three Years.

OBJECTIVES: Since physical activity (PA) has demonstrated benefits for cardiovascular health, it is possible to hypothesize that higher or increasing PA slows the progression of white matter hyperintensities (WMH). We investigated the association between PA and the progression of WMH in non-demented older adults with memory complaints. DESIGN: We included 152 participants (mean age 74.7±3.8 years; 63.8% women) in the analyses, in whom information on self-reported PA and MRI was available at both baseline and 3-year follow-up. From the PA questionnaire, the baseline metabolic equivalent of task (MET-minute/week) and changes in MET-minute/week over three years were separately calculated for overall, leisure-time, and non-leisure time PA. WMH volume at baseline and 3-year follow-up was obtained by using an automated segmentation algorithm. RESULTS: Mixed-effect linear regression models showed that none of the baseline PA variables was associated with progression of WMH over time. People who had decreased their PA levels over three years tended to show greater progression of WMH compared with those who had maintained PA levels of ≥1200 MET-min/week (roughly equivalent to ≥300 minutes of brisk walking) in the unadjusted model (ß±SE=4.85±2.42, p=0.045); however, this association was no longer significant after adjustment for confounders (ß±SE =3.63±2.18, p=0.096). CONCLUSIONS: We did not find any significant association between PA and WMH in non-demented older adults with memory complaints. However, decrease over time in PA levels tended to be associated with progression of WMH. A larger longitudinal study with data on PA assessed using objective measures would provide important information in this field.

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.

Physical Activity and ß-Amyloid Brain Levels in Humans: A Systematic Review.

Physical activity (PA) contributes to brain health and plasticity, which suggests that PA would protect against the development of Alzheimer's disease (AD). However, research on PA and AD biomarkers is very scarce. The objective of the present study was to perform a systematic review of studies that investigated the associations between PA and ß-amyloid brain deposition in humans. Electronic searches were performed in PubMed, Cochrane Library, SportDiscus, PEDro, and PsychInfo databases. Articles were eligible if they have assessed both PA and ß-amyloid brain deposition in humans. Five articles, published between 2010 and 2013, met eligibility criteria (study population varied across studies from 54 to 515, according with the ß-amyloid measure. All five studies assessed both PA and PET-amyloid; among them, two studies also assessed CSF Aß42 levels). All studies were based on cross-sectional data, from non-demented populations. Among the five included studies, three found significant associations between PA and ß-amyloid brain deposition, and the other two did not find any significant association; limited evidence suggests that PA-amyloid plaques associations would be APOE ε4 allele-specific. In sum, no solid conclusions can be drawn on the associations between PA and human ß-amyloid brain deposition currently. Future research on this topic should particularly pay attention to the operationalisation of clinically relevant and valid PA variables and should include important confounders in multivariate analysis. More information is needed on the potential interactions between PA and other AD risk factors (e.g., cognitive activities, APOE ε4 status, nutrition, smoking) and their combined effects on AD biomarkers.

A multicentric individually-tailored controlled trial of education and professional support to nursing home staff: research protocol and baseline data of the IQUARE study.

BACKGROUND: Whilst the number of people living in nursing homes (NH) is expected to rise, research on NH quality is scarce. The purpose of this article is to describe the research protocol of the IQUARE study and to present its baseline data. METHODS AND DESIGN: IQUARE is a 18-month multicentric individually-tailored controlled trial of education and professional support to NH staff. The main purposes of IQUARE are to improve the quality of the health care provided in NHs and to reduce the risk of functional decline among residents. Data on internal organisation and residents' health for the 175 participating NHs were recorded by NH staff at baseline. NHs were allocated to either a light intervention group (LIG, n = 90 NHs, totalising 3 258 participants) or a strong intervention group (SIG, n = 85 NHs, totalising 3 017 participants). Intervention for LIG consisted at delivering to NH staff descriptive statistics on indicators of quality regarding their NH and the NHs from their sub-region of health and region; whereas for SIG, NH staff received the same information that LIG, but quality indicators were discussed by a cooperative work (two half-day meetings) between a hospital geriatrician and NH staff. Strategies for overcoming NH's weaknesses were then traced; the efficacy of strategies is evaluated at a 6-month period. RESULTS: Baseline data showed high levels of dependence, comorbidities, psychological disturbances and medication's consumption among NH residents. Large discrepancies among NHs were observed. CONCLUSIONS: IQUARE is one of the largest controlled trials in NHs developed in France. Results from IQUARE may constitute the basis for the development of new work modalities within the French health system, and serve as a model of a feasible research approach in NHs.