Cross-sectional interactive associations of physical activity and sedentary behaviour with physical capacity across adulthood.

BACKGROUND: The way physical activity (PA) and sedentary behaviour (SB) independently and interactively modify the age-related decline in physical capacity remains poorly understood. This cross-sectional study investigated the independent and interactive associations of PA and SB with physical function and performance throughout the adult life course. METHODS: Data from 499 community-dwelling adults (63% female) aged 20-92 years, involved in the INSPIRE Human Translational Cohort, were used in this cross-sectional study. Daily time spent on moderate-to-vigorous PA (MVPA, min/day) and SB (h/day) was measured with activPAL triaxial accelerometers. Physical function and performance were assessed through the measurement of the 4-m usual gait speed (m/s), handgrip strength (kg), lower-limb strength (isokinetic knee extension torque, N·m), estimated lower-limb power (five-time chair-rise test performance, s) and cardiorespiratory fitness (V̇O2max, mL/kg/min). Confounder-adjusted multiple linear and curvilinear regressions were performed to investigate how MVPA, SB and their interactions were associated with the physical outcomes (all square root-transformed except gait speed) throughout the adulthood spectrum. RESULTS: Interaction analyses revealed that the combination of higher levels of MVPA with lower levels of SB favourably reshaped the negative relationship between handgrip strength and age (age2 × SB × MVPA: B = -7E-08, SE = 3E-08, P < 0.05). In addition, higher levels of MVPA were independently associated with an improved age-related profile in gait speed (age2 × MVPA: B = 3E-06, SE = 1E-06, P < 0.05), chair-rise performance (age × MVPA: B = -9E-05, SE = 4E-05, P < 0.05) and V̇O2max (MVPA at 21 years: B = 3E-02, SE = 7E-03, P < 0.05; age × MVPA: B = -5E-04, SE = 2E-04, P < 0.05). Conversely, the detrimental association of age with lower-limb muscle strength (age × SB: B = -1E-04, SE = 6E-05, P < 0.05) and chair-rise performance (age × SB: B = 1E-05, SE = 7E-06, P < 0.05) was exacerbated with increasing duration of SB, independently of MVPA. Supplementary analyses further revealed that some of these associations were age and sex specific. CONCLUSIONS: This cross-sectional study demonstrated that reduced sedentary time and increased activity duration were independently and synergistically associated with an attenuated age-related loss in physical capacity. These findings need to be confirmed with longitudinal data but encourage both adopting an active lifestyle and reducing sedentary time as preventive measures against physical aging.

Association of physical behaviours with sarcopenia in older adults: a systematic review and meta-analysis of observational studies.

BACKGROUND: Physical behaviours (ie, physical activity and sedentary behaviour) might have a role in the development of sarcopenia, although the evidence is unclear. We aimed to explore the association of total and intensity-specific levels of physical activity and sedentary behaviour with sarcopenia and its components (ie, muscle mass, muscle strength, and physical performance) in older adults. METHODS: We conducted a systematic review and meta-analysis and searched MEDLINE (via PubMed), Scopus, and Web of Science from inception to July 26, 2022, for peer-reviewed, observational studies or baseline data from randomised clinical trials conducted in older adults (ie, individual age ≥60 years or mean age ≥65 years) and published in English that reported on the association of physical activity or sedentary behaviour or both with sarcopenia (or its determinants: muscle mass or strength, and physical performance). Physical activity and sedentary behaviour were measured by any method. The main outcome was sarcopenia, which could be diagnosed by any means. Estimates were extracted and pooled using Bayesian meta-analytic models and publication bias was assessed using the Egger's test. This study is registered with PROSPERO, CRD42022315865. FINDINGS: We identified 15 766 records, of which 124 studies (230 174 older adults; 121 301 [52·7%] were female and 108 873 [47·3%] were male) were included in the systematic review. 86 studies were subsequently included in the meta-analysis. Higher levels of total physical activity were inversely associated with sarcopenia both cross-sectionally (21 studies, n=59 572; odds ratio 0·49, 95% credible interval 0·37-0·62) and longitudinally (four studies, n=7545; 0·51, 0·27-0·94). A protective association was also identified for moderate-to-vigorous physical activity in cross-sectional research (five studies, n=6787; 0·85, 0·71-0·99), whereas no association was identified for the remaining physical behaviours (ie, steps, light physical activity, or sedentary behaviour). INTERPRETATION: Total and moderate-to-vigorous physical activity are inversely associated with sarcopenia. These findings might support the importance of moderate-to-vigorous, rather than light, intensity physical activity-based interventions to prevent sarcopenia. FUNDING: None. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Plasma Level of ATPase Inhibitory Factor 1 and Intrinsic Capacity in Community-Dwelling Older Adults: Prospective Data From the MAPT Study.

BACKGROUND: Intrinsic capacity (IC) is a concept related to functionality that reflects healthy aging. ATPase inhibitory factor 1 (IF1) is a multifaceted protein that regulates mitochondrial oxidative phosphorylation (OXPHOS), and may be involved in IC. The objective of this study is to investigate the association between plasma levels of IF1 and IC changes in community-dwelling older adults. METHODS: Community-dwelling older adults from the Multidomain Alzheimer Preventive Trial (MAPT Study) were enrolled in this study. A composite IC score was calculated based on 4 IC domains: locomotion, psychological dimension, cognition, and vitality (with data available annually over 4 years of follow-up). Secondary analyses were conducted on the sensory domain (with data available only for 1 year of follow-up). Mixed-model linear regression adjusted for confounders was conducted. RESULTS: A total of 1 090 participants with usable IF1 values were included in the study (75.3 ± 4.4 years; 64% females). Compared to the lowest quartile, both the low- and high-intermediate IF1 quartiles were found to be cross-sectionally associated with greater composite IC scores across 4 domains (ßlow-intermediate, 1.33; 95% confidence interval [CI] 0.06-2.60 and ßhigh-intermediate, 1.78; 95% CI 0.49-3.06). In the secondary analyses, the highest quartile was found to be associated with a slower decline in composite IC scores across 5 domains over 1 year (ßhigh 1.60; 95% CI 0.06-3.15). The low- and high-intermediate IF1 quartiles were also found to be cross-sectionally associated with greater locomotion (ßlow-intermediate, 2.72; 95% CI 0.36-5.08) and vitality scores (ßhigh-intermediate, 1.59; 95% CI 0.06-3.12), respectively. CONCLUSIONS: This study is the first to demonstrate that levels of circulating IF1, a mitochondrial-related biomarker, are associated with IC composite scores in both cross-sectional and prospective analyses among community-dwelling older adults. However, further research is needed to confirm these findings and elucidate the potential underlying mechanisms that may explain these associations.

Associations Between Blood Nutritional Biomarkers and Cerebral Amyloid-ß: Insights From the COGFRAIL Cohort Study.

Understanding the relationship between blood nutrients and neurodegeneration could contribute to devising strategies for preventing Alzheimer's disease. We investigated the associations between fatty acids, vitamins D, B6, B12, folate, homocysteine, and the cerebral load of amyloid ß (Aß). This cross-sectional study included 177 older adults (70-96 years, 65% female) with objective cognitive impairment, prefrail, or frail. Cerebral Aß load was determined using positron emission tomography Standardized Uptake Value ratios. Fatty acids were assessed in erythrocytes, vitamins D and homocysteine in serum, and the other vitamins in plasma. Linear regression models corrected for multiple comparisons evaluated the associations between each nutrient and Aß. The principal component factor followed by linear regression grouped the fatty acids strongly correlated (factor) and associated with Aß. Higher concentrations of polyunsaturated fatty acids (PUFAs): clupanodonic acid (22:5n-3; ß: -0.13; p = .001), mead acid (20:3n-9; ß: -0.07; p = .036), and adrenic acid (22:4n-6; ß: -0.05; p = .031) were associated with lower global Aß load, whereas linoleic acid (18:2n-6) was associated with higher global Aß load (ß: 0.18; p = .042). Clupanodonic acid was inversely associated with Aß in all cerebral regions except the thalamus. The factor composed of mead, clupanodonic, and arachidonic (20:4n-6) acids was associated with a lower global Aß load (ß: -0.02; p = .002). Some erythrocyte PUFAs were inversely associated with Aß load in the brain, and most of them were metabolites of the essential fatty acids linoleic and α-linolenic. Given the cross-sectional design, these results must be carefully interpreted, and longitudinal studies are needed.

Reference centiles for intrinsic capacity throughout adulthood and their association with clinical outcomes: a cross-sectional analysis from the INSPIRE-T cohort.

Intrinsic capacity (IC), a function-centered construct, is defined as the composite of all physical and mental capacities of an individual. IC and surrounding environmental factors determine an individual's functional ability to do what they want or feel valued. Current literature lacks evidence on how IC varies throughout adulthood. In this study, we demonstrated a method to establish age-specific and sex-specific reference centiles for IC using the Human Translational Research Cohort of the INSPIRE Platform (975 adults, aged 20-102 years, living in the southwest France, Toulouse area). IC was operationalized as the mean score of the five key domains (cognition, locomotion, psychology, sensory and vitality) and the factor score from a bifactor model, respectively. Both IC operationalizations showed higher IC levels in young and middle age and markedly lower levels after age 65 years, with greater inter-individual variation in old age than in youth. Individuals with IC ≤10th percentile tended to have high comorbidity, prefrailty/frailty, difficulties in basic and instrumental activities of daily living and falls than individuals with IC >90th percentile. These findings suggest that IC reference centiles can help monitor the functional capacity of individuals during aging, similar to tracking children's development with growth charts.

Associations between physical activity levels and ATPase inhibitory factor 1 concentrations in older adults.

BACKGROUND: Adenosine triphosphatase inhibitory factor 1 (IF1) is a key protein involved in energy metabolism. IF1 has been linked to various age-related diseases, although its relationship with physical activity (PA) remains unclear. Additionally, the apolipoprotein A-I (apoA-I), a PA-modulated lipoprotein could play a role in this relationship because it shares a binding site with IF1 on the cell-surface ATP synthase. We examined here the associations between chronic PA and plasma IF1 concentrations among older adults, and we investigated whether apoA-I mediated these associations. METHODS: In the present work, 1096 healthy adults (63.8% women) aged 70 years and over who were involved in the Multidomain Alzheimer Prevention Trial study were included. IF1 plasma concentrations (square root of ng/mL) were measured at the 1-year visit of the Multidomain Alzheimer Prevention Trial, while PA levels (square root of metabolic equivalent task min/week) were assessed using questionnaires administered each year from baseline to the 3-year visit. Multiple linear regressions were performed to investigate the associations between the first-year mean PA levels and IF1 concentrations. Mediation analyses were conducted to examine whether apoA-I mediated these associations. Mixed-effect linear regressions were carried out to investigate whether the 1-year visit IF1 concentrations predicted subsequent changes in PA. RESULTS: Multiple linear regressions indicated that first-year mean PA levels were positively associated with IF1 concentrations (B = 0.021; SE = 0.010; p = 0.043). Mediation analyses revealed that about 37.7% of this relationship was mediated by apoA-I (Bab = 0.008; SE = 0.004; p = 0.023). Longitudinal investigations demonstrated that higher concentrations of IF1 at the 1-year visit predicted a faster decline in PA levels over the subsequent 2 years (time × IF1: B = -0.148; SE = 0.066; p = 0.025). CONCLUSION: This study demonstrated that regular PA is associated with plasma IF1 concentrations, and it suggests that apoA-I partly mediates this association. Additionally, this study found that baseline concentrations of IF1 can predict future changes in PA. However, further research is needed to fully understand the mechanisms underlying these observations.

Challenges in developing Geroscience trials.

Geroscience is becoming a major hope for preventing age-related diseases and loss of function by targeting biological mechanisms of aging. This unprecedented paradigm shift requires optimizing the design of future clinical studies related to aging in humans. Researchers will face a number of challenges, including ideal populations to study, which lifestyle and Gerotherapeutic interventions to test initially, selecting key primary and secondary outcomes of such clinical trials, and which age-related biomarkers are most valuable for both selecting interventions and predicting or monitoring clinical responses ("Gerodiagnostics"). This article reports the main results of a Task Force of experts in Geroscience.

Association between aging-related biomarkers and longitudinal trajectories of intrinsic capacity in older adults.

Intrinsic capacity (IC), the composite of physical and mental capacities, declines with age at different rates and patterns between individuals. We aimed to investigate the association between longitudinal IC trajectories and plasma biomarkers of two hallmarks of aging-chronic inflammation and mitochondrial dysfunction-in older adults. From the Multidomain Alzheimer Preventive Trial (MAPT), we included 1271 community-dwelling older people (mean [SD] age = 76.0 [4.3] years) with IC data over four years. Group-based multi-trajectory modeling was performed to identify clusters of the participants with similar longitudinal patterns across four IC domains: cognition, locomotion, psychology, and vitality. Five IC multi-trajectory groups were determined: low in all domains (8.4%), low locomotion (24.6%), low psychological domain (16.7%), robust (i.e., high in all domains except vitality; 28.3%), and robust with high vitality (22.0%). Compared to the best trajectory group (i.e., robust with high vitality), elevated levels of plasma interleukin-6 (IL-6), tumor necrosis factor receptor-1 (TNFR-1), and growth differentiation factor-15 (GDF-15) were associated with a higher risk of belonging to the "low in all domains" group (IL-6: relative risk ratio (RRR) [95% CI] = 1.42 [1.07 - 1.88]; TNFR-1: RRR = 1.46 [1.09 - 1.96]; GDF-15: RRR = 1.99 [1.45 - 2.73]). Higher IL-6 and GDF-15 also increased the risk of being in the "low locomotion" group. GDF-15 outperformed other biomarkers by showing the strongest associations with IC trajectory groups. Our findings found that plasma biomarkers reflecting inflammation and mitochondrial impairment distinguished older people with multi-impaired IC trajectories from those with high-stable IC.

The sensitivity and specificity of the WHO's ICOPE screening tool, and the prevalence of loss of intrinsic capacity in older adults: A scoping review.

BACKGROUND: The World Health Organization has developed the Integrated Care for Older People (ICOPE) program, a public health strategy to maintain older adults' functional abilities and promote healthier aging. The approach comprises a 5-step pathway. Step 1 is the screening for impairment in functions, and Step 2 is an in-depth evaluation to confirm the presence and severity of functional impairment. These initial two steps are crucial to determine the subsequent plan of care (Step 3) and follow-up (Step 4). The fifth step encompasses actions to support families and caregivers and to engage communities. This review gathers data from the literature on the prevalence of positive screenings regarding intrinsic capacity detected by the program's first-step screening tool, and on currently available results regarding the instrument's sensitivity and specificity. METHODS AND FINDINGS: Electronic searches were conducted in the PubMed, Cochrane, Embase, and SciElo databases, the medRxiv platform, and recent human aging scientific events, looking for research analyzing the ICOPE screening instrument. Studies reporting data on the prevalence of positive screenings for loss of intrinsic capacity using the proposed screening tool and/or findings on the instrument's sensitivity and specificity were included. A total of 7 publications with participants aged 50 years or more were selected. The prevalence of at least one impairment in intrinsic capacity detected by the instrument varied among the studies from 17.1 % to 94.3 %. Sensitivity ranged from 26.4 % to 100 % and specificity from 22 % to 96 %, depending on the setting and the assessed domain. CONCLUSION: Currently available data are heterogeneous, and different results were found among the studies due to diverse settings and methodologies. The evidence on the ICOPE screening tool's performance in different populations is still scarce and reinforces the need for further research worldwide.

Fatigue in Alzheimer's disease: biological basis and clinical management-a narrative review.

BACKGROUND: Fatigue is a common symptom in neurodegenerative diseases and is associated with decreased cognitive performances. A full knowledge of the causes and physiopathological pathways leading to fatigue in Alzheimer's disease could help treating this symptom and obtain positive effects on cognitive functions. OBJECTIVES: To provide an overview of the clinical conditions and the biological mechanisms leading to fatigue in Alzheimer's disease patients. To review the recent advances on fatigue management and describe the landscape of future possibilities. METHODS: We performed a narrative review including all type of studies (e.g. cross-sectional and longitudinal analysis, reviews, clinical trials). RESULTS: We found very few studies considering the symptom fatigue in Alzheimer's disease patients. Populations, designs, and objectives varied across studies rendering comparability across studies difficult to perform. Results from cross-sectional and longitudinal analysis suggest that the amyloid cascade may be involved in the pathogenesis of fatigue and that fatigue may be a prodromal manifestation of Alzheimer's disease. Fatigue and neurodegeneration of Alzheimer's disease could share common brain signatures (i.e. hippocampal atrophy and periventricular leukoaraiosis). Some mechanisms of aging (i.e. inflammation, mitochondrial dysfunction, telomere shortening) may be proposed to play a common underlying role in Alzheimer's disease neurodegeneration and muscle fatigability. Considering treatments, donepezil has been found to reduce cognitive fatigue in a 6-week randomized controlled study. Fatigue is frequently reported as an adverse event in patients treated by anti-amyloid agents in clinical trials. CONCLUSION: The literature is actually inconclusive about the main causes of fatigue in Alzheimer's disease individuals and its potential treatments. Further research is needed to disentangle the role of several components such as comorbidities, depressive symptoms, iatrogenic factors, physical decline and neurodegeneration itself. Given the clinical relevance of this symptom, it seems to be important to systematically assess fatigue by validated tools in Alzheimer's disease clinical trials.

Investigating three ways of measuring the intrinsic capacity domain of vitality: nutritional status, handgrip strength and ageing biomarkers.

BACKGROUND: Vitality is conceptually considered as the underlying capacity influencing other intrinsic capacity (IC) domains and being related to nutrition, physiological reserve and biological ageing. However, there is no consensus on its operationalisation. OBJECTIVE: To investigate the structure and magnitude of the association of vitality with other IC domains and functional difficulties using three operational definitions of vitality. METHODS: We included 1,389 older adults from the Multidomain Alzheimer Preventive Trial with data on Mini Nutritional Assessment (MNA), handgrip strength and plasma biomarkers (comprising inflammatory and mitochondrial markers). Using path analysis, we examined the effects of vitality on difficulties in basic and instrumental activities of daily living (ADL and IADL) exerted directly and indirectly through the mediation of other IC domains: cognition, locomotion, psychological, vision and hearing. We further explored the longitudinal association of vitality with IC domains, ADL and IADL over 4 years using linear mixed-effect regression. RESULTS: We observed significant indirect effects of vitality on IADL, mainly through cognitive, locomotor and psychological domains, regardless of the vitality measurement. Participants with higher vitality had fewer IADL difficulties at follow-up (MNA score: ß [95% CI] = -0.020 [-0.037, -0.003]; handgrip strength: -0.011 [-0.023, 0.000]; plasma biomarker-based index: -0.015 [-0.028, -0.002]). Vitality assessed with the plasma biomarker-based index predicted improved locomotion over time. CONCLUSION: Vitality was associated with disability primarily through the mediation of other IC domains. The three indicators examined are acceptable measurements of vitality; biomarkers might be more suitable for the early detection of locomotion decline.

Cross-sectional associations of dietary intake with hearing and vision capacities and potential mediation effect of inflammation in older adults: the COGFRAIL study.

BACKGROUND: Considering their prevalence and burden, information on the sensory impairment etiology is essential. Links between nutrition and sensory impairment through inflammation have been suggested. Although the decline in sensory capacities is age-related, few research included a geriatric population. AIMS: Exploring the associations of nutrition with sensory capacities and test inflammation as a mediator among cognitively and physically impaired older adults. METHODS: Cross-sectional data from the COGFRAIL cohort, including 164 participants with no hearing aid and 20 participants wearing no visual aid. Hearing was evaluated using the Hearing Handicap Inventory for the Elderly-screening version (on 40 points, the lower the better), and the Monoyer chart (one to ten out of ten points, the higher the better), and the Parinaud scale (from 1.5, the best, to 28 points, the worst) assessed distant and near vision, respectively. Dietary intake was assessed through a diet history interview and inflammation was measured by the C-Reactive Protein level. Multivariate linear regressions were performed and Structural Equation Modeling (SEM) framework was used to explore the potential mediation effect of inflammation on the diet-hearing relationships. RESULTS: None of the nutrients was significantly associated with hearing acuity in the regressions or the SEM model. Regarding vision, a higher intake of saturated fatty acids was related to lower long-distance visual acuity, and greater Omega-3 consumption was associated with better near-vision capacity. DISCUSSION: No nutrient was associated with hearing capacity and relationships between fatty acids quality and vision acuity were suggested. CONCLUSION: These exploratory results require further investigations.

Associations between Vitality/Nutrition and the Other Domains of Intrinsic Capacity Based on Data from the INSPIRE ICOPE-Care Program.

BACKGROUND: The vitality domain of intrinsic capacity (IC) represents the synthesis of biological interactions and metabolism. As part of the Integrated Care for Older People (ICOPE) program developed by the World Health Organization (WHO), vitality focuses on the nutritional status of older adults. The objective of this work was to describe the vitality domain of IC in community-dwelling older people and to examine the associations of the vitality components (appetite loss and weight loss) with the other IC domains assessed within the framework of ICOPE. METHODS: Cross-sectional data were obtained between January 2020 and February 2022 through the INSPIRE-ICOPE-Care program, a real-life ICOPE implementation initiative developed in the Occitania region of France. Participants were men and women aged 60 and older, looking for primary care services within the French healthcare system. RESULTS: Appetite loss was reported by 14.0% (2013) of the participants, and weight loss by 12.4% (1788). A total of 863 participants (6.01%) declaring weight loss also suffered from appetite loss. In total, 2910 participants (20.27%) screened positive for the domain of vitality. Appetite loss was significantly associated with positive screenings for the domains of cognition (OR = 2.14 [1.84;2.48]), vision (OR = 1.51 [1.28;1.79]), hearing (OR = 1.18 [1.01;1.37]), psychology (OR = 3.95 [3.46;4.52]), and locomotion 'OR = 2.19 [1.91;2.51]). We found significant associations of weight loss with the IC domains of cognition (OR = 1.65 [1.42;1.93]), psychology (OR = 1.80 [1.56;2.07]), locomotion (OR = 1.64 [1.41;1.91]), vision (OR = 1.24 [1.04;1.47]), and hearing (OR = 1.32 [1.12;1.55]). People reporting simultaneous appetite and weight loss showed higher odds of screening positive for psychological (OR = 5.33 [4.53;6.27]) and locomotion impairments (OR = 3.38 [2.88;3.98]). CONCLUSIONS: Appetite and weight loss are common among older people and are related to other potential IC impairments, especially psychological and locomotion. Further studies are needed to explore the longitudinal associations of vitality with the incidence of clinically meaningful declines in the other IC domains.

The role of dietary strategies in the modulation of hallmarks of aging.

The hallmarks of aging constitute an interconnected network of basic mechanisms that modulate aging and can be modulated by lifestyle factors, including dietary strategies. This narrative review aimed to summarize the evidence on promoting dietary restriction or adherence to specific dietary patterns on hallmarks of aging. Studies with preclinical models or humans were considered. Dietary restriction (DR), usually operationalized as a reduction in caloric intake, is the main strategy applied to study the axis diet-hallmarks of aging. DR has been shown to modulate mainly genomic instability, loss of proteostasis, deregulating nutrient sensing, cellular senescence, and altered intercellular communication. Much less evidence exists on the role of dietary patterns, with most of the studies evaluating the Mediterranean Diet and other similar plant-based diets, and the ketogenic diet. Potential benefits are described in genomic instability, epigenetic alterations, loss of proteostasis, mitochondrial dysfunction, and altered intercellular communication. Given the predominant place of food in human life, it is imperative to determine the impact of nutritional strategies on the modulation of lifespan and healthspan, considering applicability, long-term adherence, and side effects.

Pneumonia-Associated Emergency Transfers, Functional Decline, and Mortality in Nursing Home Residents.

OBJECTIVE: To describe nursing home residents (NHRs) transferred to the emergency department (ED) with pneumonia, and investigate the association of pneumonia with functional ability and mortality. DESIGN: Case-control observational multicenter study. SETTING AND PARTICIPANTS: Participants of the FINE study, including 1037 NHRs presenting to 17 EDs in France over 4 nonconsecutive weeks (1 per season) in 2016, mean age 87.2 years ± 7.1, 68.4% women. METHODS: Activities of daily living (ADL) performance evolution between (1) 15 days before transfer and (2) within 7 days after discharge back to the nursing home was compared in NHRs with or without pneumonia. The association of pneumonia with functional evolution was investigated by a mixed-effect linear regression of ADL and mortality was compared by a χ2 test. RESULTS: NHRs with pneumonia (n = 232; 22.4%) were more likely to have a lower ADL performance than NHRs without pneumonia (n = 805, 77.6%). They presented with a more severe clinical condition, were more likely to be hospitalized after ED and to stay longer in ED and in hospital. They showed a 0.5 decline in median ADL performance after transfer and a significantly higher mortality than NHRs without pneumonia (24.1% and 8.7%, respectively). Post-ED functional evolution did not differ significantly between NHRs with or without pneumonia. CONCLUSIONS AND IMPLICATIONS: Pneumonia-associated ED transfers resulted in longer care pathways and higher mortality, but no significant difference in functional decline. This study identified a suggestive course of symptoms that could facilitate early identification of NHRs developing pneumonia and early management to prevent ED transfer.

Association between physical activity, growth differentiation factor 15 and bodyweight in older adults: A longitudinal mediation analysis.

BACKGROUND: Late-life aging is often associated with appetite reduction and weight loss. Physical activity (PA) may prevent these processes, but the molecular mechanisms involved remain elusive. The present study investigated the putative mediating aspect of growth differentiation factor 15 (GDF-15), a stress signalling protein involved in aging, exercise and appetite control, on the association between PA and late-life-associated weight loss. METHODS: One thousand eighty-three healthy adults (63.8% women) aged 70 years and over who participated in the Multidomain Alzheimer Preventive Trial were included. Bodyweight (kg) and PA levels (square root of metabolic equivalent of task-min/week) were assessed repeatedly from baseline to the 3-year visit, whereas plasma GDF-15 (pg/mL) was measured at the 1-year visit. Multiple linear regressions were performed to test the association between first-year mean PA level, 1-year visit GDF-15 concentration and subsequent bodyweight changes. Mediation analyses were used to investigate whether GDF-15 mediated the association between first-year mean PA levels and consecutive bodyweight changes. RESULTS: Multiple regression analyses demonstrated that higher first-year mean PA levels significantly predicted lower GDF-15 and bodyweight at 1 year (B = -2.22; SE = 0.79; P = 0.005). In addition, higher 1-year visit GDF-15 levels were associated with faster subsequent bodyweight loss (Time × GDF-15 interaction B = -0.0004; SE = 0.0001; P = 0.003). Mediation analyses confirmed that GDF-15 mediated the association between first-year mean PA levels and subsequent bodyweight changes (mediated effect ab = 0.0018; bootstrap SE = 0.001; P < 0.05) and revealed that mean PA had no direct effect on subsequent bodyweight changes (c' = 0.006; SE = 0.008; P > 0.05). CONCLUSIONS: This study suggests that GDF-15 may be one of the molecules mediating the link between PA and late-life weight loss, but mechanistic studies are necessary to further support the present findings.

Plasma inflammation-related biomarkers are associated with intrinsic capacity in community-dwelling older adults.

BACKGROUND: How inflammation relates to intrinsic capacity (IC), the composite of physical and mental capacities, remains undefined. Our study aimed to investigate the cross-sectional and longitudinal associations between plasma inflammation-related biomarkers and IC in older adults. METHODS: This secondary analysis of the Multidomain Alzheimer Preventive Trial (MAPT) included 1238 community-dwelling older individuals with IC assessments from 12 to 60 months. Plasma C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor receptor-1 (TNFR-1), monocyte chemoattractant protein-1 (MCP-1) and growth differentiation factor-15 (GDF-15) were measured at 12 months. IC was operationalized as a score ranging from 0 to 100, derived from four domains: cognition, Mini-Mental State Examination; locomotion, Short Physical Performance Battery; psychological, Geriatric Depression Scale; and vitality, handgrip strength. A five-domain IC score (plus sensory) was investigated in a subsample (n = 535) with a 1-year follow-up as an exploratory outcome. RESULTS: The mean age of the 1238 participants was 76.2 years (SD = 4.3); 63.7% were female. Their initial four-domain IC scores averaged 78.9 points (SD = 9.3), with a yearly decline of 1.17 points (95% CI = -1.30 to -1.05; P < 0.001). We observed significant associations of lower baseline IC with higher CRP, IL-6, TNFR-1 and GDF-15, after controlling age, sex, MAPT group allocation and educational level [CRP: adjusted ß (95% CI) = -1.56 (-2.64 to -0.48); P = 0.005; IL-6: adjusted ß = -3.16 (-4.82 to -1.50); P < 0.001; TNFR-1: adjusted ß = -6.86 (-10.25 to -3.47); P < 0.001; GDF-15: adjusted ß = -7.07 (-10.02 to -4.12); P < 0.001]. Higher TNFR-1, MCP-1 and GDF-15 were associated with faster decline in four-domain IC over 4 years [TNFR-1: adjusted ß (95% CI) = -1.28 (-2.29 to -0.27); P = 0.013; MCP-1: adjusted ß = -1.33 (-2.24 to -0.42); P = 0.004; GDF-15: adjusted ß = -1.42 (-2.26 to -0.58); P = 0.001]. None of the biomarkers was significantly associated with the five-domain IC decline. CONCLUSIONS: Inflammation was associated with lower IC in older adults. Among all plasma biomarkers, TNFR-1 and GDF-15 were consistently associated with IC at the cross-sectional and longitudinal levels.

Development and Validation of a Cutoff for the Chair Stand Test as a Screening for Mobility Impairment in the Context of the Integrated Care for Older People Program.

BACKGROUND: The 5-repetition chair stand test (CST) is increasingly being used to assess locomotion capacity in older adults. However, there is a lack of age-stratified cutoffs for adults aged ≥70 validated against a higher risk of functional loss. METHODS: We used 2 population-based studies (Study on global AGEing and adult health in Mexico [SAGE Mexico] and Toledo Study for Healthy Aging [TSHA]) and receiver operating characteristic (ROC) analyses to develop and cross-validate age-stratified chair stand cutoffs with activities of daily living (ADL) disability as the outcome. Then, we used data from an randomized controlled trial (RCT) (Multidomain Alzheimer Preventive Trial [MAPT]) and a frailty day-hospital for external validation with cross-sectional and longitudinal measures of ADL disability. The merged sample of SAGE Mexico and TSHA was n = 1 595; sample sizes for external validation were: MAPT n = 1 573 and Frailty day-hospital n = 2 434. The Cox models for incident disability in MAPT had a mean follow-up of 58.6 months. RESULTS: Cutoffs obtained were 14 second (ages 70-79) and 16 second (ages 80+). Those cutoffs identified older adults at higher odds of incident ADL disability odds ratio (OR) = 1.72 (95% confidence interval [CI] 1.06; 2.78) for ages 70-79 and odds ratio (OR) = 2.27 (95% CI 1.07; 4.80) in those aged 80+. Being a slow chair stander according to the cut points was associated with ADL disability in cross-sectional and longitudinal measures. CONCLUSIONS: Fourteen- and 16-second cut points for the CST are suitable to identify people at higher risk of functional decline among older adults in Mexico and Toledo, Spain. Adjusting the cut point from 14 to 16 second generally improved the psychometric properties of the test. The validation of these cutoffs can facilitate the screening for limited mobility and the implementation of the Integrated Care for Older People program.