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.

Ready-meal consumption in older people: association with obesity and dietary intake.

OBJECTIVE: To investigate ready-meal consumption trends in older French people, its association with overall diet quality and obesity. DESIGN: Cross-sectional analysis SETTING: Multidomain Alzheimer Preventive Trial (MAPT), France SUBJECTS: 421 MAPT participants (mean age 76.8 years) who filled a food frequency questionnaire. RESULTS: The frequency of ready-meal consumption was low, with nearly 90% of participants declaring consuming ≤ 1 ready-meal per week. Compared to non- and low-consumers (≤ 1 ready-meal/week), regular consumers (≥ 2 ready-meals/week) were older (p < 0.01), more often frail and pre-frail (p 0.04), with impaired cognition (p = 0.02) and functional status (p = 0.02), with more depressive symptoms (p = 0.03) and more difficulties with preparing meals (p = 0.01). Results from multivariate analyses showed that regular ready-meal consumption was not associated with obesity (p = 0.26) and diet quality (p = 0.37). CONCLUSIONS: In our sample, few older people declared consumption of 2 or more ready-meals per week, this consumption was not associated with a higher prevalence of obesity or a lower diet quality, despite the fact that these subject were older, with a lower physical and cognitive status. These findings suggest that, for these people with difficulties in meal preparation, convenience foods consumed occasionally could help to maintain diet quality and weight status.

Distinct effect of age, sex, and CMV seropositivity on dendritic cells and monocytes in human blood.

We analyzed the impact of age, sex, and CMV on blood monocyte and dendritic cell (DC) subpopulations in 256 healthy individuals aged from 19 to 96 years. Flow cytometry was performed on whole blood within the 4 h following blood drawing. Myeloid (mDC) and plasmacytoid DC (pDC), classical, intermediate, and nonclassical monocytes were enumerated by means of TruCount tubes (BD Biosciences). We provided reference values for mDC, pDC and the three monocyte subpopulations. The numbers of classical, intermediate, and nonclassical monocytes slightly increased with age while the numbers of mDC and pDC did not vary significantly. The level of expression of CD64 and CD163 on monocytes significantly increased with age while HLA-DR expression did not vary significantly. More precisely, CD163 expression level on intermediate monocyte slightly increased with age in women only (Spearman P = 0.019) while CD64 expression increased on monocytes in CMV-positive individuals only. We observed that sex had almost no impact on the numbers of monocytes and DC and on their expression level of CD64 and HLA-DR. We observed a significant decrease in the numbers of pDC with age in CMV-positive individuals, but not in CMV negative individuals. This suggests that the lifelong subclinical infection by CMV could influence the number of circulating DC of lymphoid origin. In contrast, CMV serostatus had no significant impact on absolute numbers of mDC and monocytes.

Cross-sectional associations of cortical ß-amyloid with erythrocyte membrane long-chain polyunsaturated fatty acids in older adults with subjective memory complaints.

Omega-3 (n-3) and 6 (n-6) polyunsaturated fatty acids (PUFAs) have been associated with reduced cognitive decline in observational studies. Hence, we examined the cross-sectional associations between cortical ß-amyloid (Aß) and erythrocyte membrane PUFAs in 61 non-demented elderly individuals reporting subjective memory complaints from the Multidomain Alzheimer Preventive Trial placebo arm. Cortical-to-cerebellar standard uptake value ratios were obtained using [18 F] florbetapir positron emission tomography. Fatty acids were measured in erythrocyte membranes by gas chromatography. Associations were explored using adjusted multiple linear regression models and were considered significant at p ≤ 0.005 after correction for multiple testing (10 comparisons). We found no significant associations between cortical Aß and erythrocyte membrane PUFAs. The associations closest to significance after adjustment were those between Aß and erythrocyte membrane arachidonic acid (without apolipoprotein E status adjustment: B-coefficient, 0.03; CI, 0.01, 0.05; p = 0.02. Including Apolipoprotein E adjustment: B-coefficient, 0.03; CI, 0.00, 0.06; p = 0.04) and Aß and erythrocyte membrane linoleic acid (without apolipoprotein E status adjustment: B-coefficient, -0.02; CI, -0.04, 0.00; p = 0.02. Including Apolipoprotein E adjustment: B-coefficient, -0.02; CI, -0.04, 0.00; p = 0.09). Furthermore, the association between Aß and erythrocyte membrane arachidonic acid seemed to be specific to Apolipoprotein E ε4 non-carriers (B-coefficient 0.03, CI: 0.00, 0.06, p = 0.03, n = 36). In contrast, no association was found between Aß and erythrocyte membrane linoleic acid in Apolipoprotein E ε4 stratified analysis. Investigating the relationships between Aß and PUFAs longitudinally would provide further evidence as to whether fatty acids, particularly arachidonic acid and linoleic acid, might modulate cognition through Aß-dependent mechanisms.

Assessing Alzheimer's disease patients' quality of life: Discrepancies between patient and caregiver perspectives.

INTRODUCTION: Quality of life (QOL) is an important dimension to consider in Alzheimer's disease (AD), but few large-scale studies have analyzed self and caregiver reports of patient QOL. METHODS: Patient QOL was evaluated in a cohort of 574 AD patients with the QOL-AD scale over 2 years. RESULTS: Caregiver reports of patient QOL were lower at baseline than self reports. Older patient age was associated with overestimation of QOL by caregivers, whereas neuropsychiatric inventory score and caregiver burden were associated with underestimation. Activities of daily living limitation, depressive symptoms, and caregiver burden were systematically associated with poorer QOL, whereas caregiver relationship and apathy were associated with poorer QOL only for self reports or caregiver reports, respectively. Cognitive function and professional care were not associated with QOL. Self-rated patient QOL did not change over time, whereas disease severity markers and caregiver-rated patient QOL declined. DISCUSSION: It is important to assess both self and caregiver ratings when assessing patient QOL.

Is nutrition important to postpone frailty?

PURPOSE OF REVIEW: The purpose of the present study is to provide an updated, systematic review of the recent literature on whether nutrition is important to postpone frailty. RECENT FINDINGS: A systematic review of recent literature (past 12 months) identified nine studies (eight of which using a cross-sectional design) exploring the relationship between nutrition and frailty. A single randomized controlled double-blind trial was published. However, being a pilot study, it was characterized by a relatively small sample size, short follow-up length (i.e., 6 months), and low statistical power. Notably, available evidence shows considerable variability in participants' selection and assessment methods, rendering difficult direct comparisons. Size effects or magnitude of associations across the different studies cannot also be determined. SUMMARY: There is a need for long-term, adequately powered, randomized controlled trials examining nutrition (alone and/or in combination with other appropriate interventions) as a means for postponing frailty in older persons.

Plasma p-tau181 as an outcome and predictor of multidomain intervention effects: a secondary analysis of a randomised, controlled, dementia prevention trial.

BACKGROUND: It is unknown whether multidomain interventions, which might preserve late-life cognition, affect Alzheimer's disease pathology. Previous studies measured cerebrospinal fluid and imaging Alzheimer's disease biomarkers in small subsamples of multidomain trial participants. Newly developed assays enable the measurement of blood-based Alzheimer's disease biomarkers in larger samples. We aimed to assess whether plasma tau phosphorylated at threonine 181 (p-tau181) was able to detect or predict 3-year multidomain intervention effects. METHODS: This is a secondary analysis of the randomised, controlled, Multidomain Alzheimer Prevention Trial (MAPT) testing a 3-year multidomain intervention, omega-3 fatty acid supplementation, or both versus placebo, in individuals aged 70 years and older in 13 memory centres in France and Monaco. Plasma p-tau181 was measured in stored blood samples in a subsample of 527 participants on an intention-to-treat basis. Changes in cognitive score were calculated as a composite measure using the average of Z scores for the following tests: Mini Mental State Examination orientation items, Free and Cued Selective Reminding Test (sum of free and total recall scores), category fluency, and Digit Symbol Substitution Test. Intervention effects on 3-year change in p-tau181 concentration were estimated by use of a linear mixed model with centre-specific random intercepts. FINDINGS: Recruitment took place between May 30, 2008, and Feb 24, 2011. Median baseline plasma p-tau181 was 8·8 pg/mL (IQR 6·7-11·9) in the total sample, and significantly higher in older individuals, men, APOE ε4 carriers, and participants with renal dysfunction or a positive PET amyloid scan. During 3-year follow-up, individuals with raised baseline p-tau181 underwent greater cognitive decline (eg, mean difference in 3-year change on the composite cognitive score between control group participants with normal and abnormal baseline levels of p-tau was -0·34 [effect size -0·52; 95% CI -0·61 to 0·07] in the fully adjusted model using a 12·4 pg/mL cutoff for abnormal baseline p-tau181), but there were no intervention effects on change in p-tau181 either in this subgroup or the total population, and no effect on cognitive change in individuals with raised baseline p-tau181 (eg, in the fully adjusted model using the 12·4 pg/mL cutoff for p-tau181 abnormality, the mean difference [95% CI] in this subgroup in 3-year decline on the composite cognitive score between the control group and the multidomain + omega-3 group, the omega-3 group, and the multidomain intervention group, was, respectively: 0·13 [-0·21 to 0·47], 0·03 [-0·30 to 0·36], and 0·10 [-0·26 to 0·46]). Surprisingly, individuals with raised baseline p-tau181 showed a decrease in p-tau181 during follow-up (eg, unadjusted mean [95% CI] 3-year change was -3·01 pg/mL (-4·45 to -1·56) in control group subjects with abnormal baseline p-tau181 [using the 12·4 pg/mL abnormal p-tau cutoff]). INTERPRETATION: Our results support the utility of p-tau181 as a prognostic biomarker, but it did not predict or detect intervention effects in this study. Further investigation of its usefulness as a prevention trial outcome measure is required. FUNDING: Toulouse Gérontopôle, French Ministry of Health and Pierre Fabre Research Institute.

Longitudinal Associations Between ATPase Inhibitory Factor 1, Growth Differentiation Factor-15, and Nutritional Status in Older Adults From the MAPT Study.

BACKGROUND: Weight and appetite regulation have been associated with the expression and secretion of ATPase inhibitory factor 1 (IF1) and growth differentiation factor-15 (GDF-15), 2 potential biomarkers for age-related mitochondrial dysfunction. The aim was to explore the associations between these biomarkers and nutritional variables in the Multidomain Alzheimer Preventive Trial study. METHODS: IF1 and GDF-15 plasma levels were quantified at 1-year follow-up. The nutritional status was measured using the Mini Nutritional Assessment (MNA) score variation between baseline and 1- and 2-year visits; appetite loss was extracted from the MNA. Bodyweight was measured every 6 months until the third year and then yearly until the fifth year of follow-up, and weight loss was established if the loss was greater than 5% or 10% within the past 6 or 12 months, respectively. Bidirectional associations of IF1 and GDF-15 levels with malnutrition, appetite, and weight loss were examined. The interactions between individual IF1 and GDF-15 with sex were explored. RESULTS: Four hundred and forty-eight participants had MNA data and 1 045 had weight loss data. All the associations between IF1 levels and the MNA score, appetite loss, and weight loss were nonsignificant. Higher GDF-15 levels were cross-sectionally associated with appetite loss at the first year of follow-up, and the GDF-15 highest quartile was associated with nearly 80% higher risks of weight loss over 4 years. Interactions between IF1 and GDF-15 levels, and between these 2 markers and sex were not significantly associated with the outcomes. CONCLUSIONS: GDF-15 plasma levels were related to key malnutrition criteria.

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.

Predictive Capacity of the Integrated Care for Older People Screening Tool for Intrinsic Capacity Impairments: Results From the INSPIRE-T Cohort.

BACKGROUND: The Integrated Care for Older People (ICOPE) approach was developed by the World Health Organization (WHO) aiming to shift the traditional focus of care based on diseases to a function- and person-centered approach, focused on maintaining and monitoring intrinsic capacity (IC). This study aimed to investigate the ability of the ICOPE screening tool to identify older people with clinically meaningful impairments in IC domains. METHODS: This cross-sectional analysis included 603 older adults, participants (mean age 74.7 [SD = 8.8] years, women 59.0%) of the INSPIRE Translational (INSPIRE-T) cohort. Responses at screening were compared to results of the subsequent in-depth assessment (ie, Mini-Mental State Examination, Mini Nutritional Assessment, Short Physical Performance Battery, Patient Health Questionnaire-9, and clinical investigation of vision problems) to determine its predictive capacity for impairments at the IC domains (ie, cognition, psychological, sensory (vision), vitality, and locomotion). RESULTS: The ICOPE screening items provided very high sensitivity for identifying abnormality in vision (97.2%) and varied from 42.0% to 69.6% for the other domains. High specificity (>70%) was observed for all the IC domains, except for vision (2.7%). CONCLUSIONS: The ICOPE screening tool can be a useful instrument enabling the identification of older people with impairments in IC domains, but studies with different populations are needed. It should be considered as a low-cost and simple screening tool in clinical care.

Visit-to-visit blood pressure variability is associated with intrinsic capacity decline: Results from the MAPT Study.

BACKGROUND: The effectiveness of the body physiological regulatory mechanisms declines in late life, and increased Blood Pressure Variability (BPV) may represent an alteration in cardiovascular homeostatic patterns. Intrinsic Capacity (IC) has been proposed by the World Health Organization as a marker of healthy aging, based on individual's functional abilities and intended at preserving successful aging. We aimed to investigate the association of visit-to-visit BPV with IC decline in a population of community-dwelling older adults. METHODS: The study population consisted of 1407 community-dwelling participants aged ≥70 years from the MAPT study evaluated during the 5-year follow-up. Systolic BPV (SBPV) and diastolic BPV (DBPV) were determined through six indicators. Cognition, psychology, locomotion and vitality constituted the four IC domains assessed. Total IC Z-score resulted from the sum of the four domains Z-scores divided by 4. The incidence of domain impairment over time was also assessed. RESULTS: Higher SBPV was significantly associated with poorer IC Z-scores in all linear mixed models [1-SD increase of CV%: ß(SE)=-0.010(0.001), p < 0.01]. Similar results were observed for DBPV [1-SD increase of CV%: ß(SE)=-0.003(0.001), p = 0.02]. Incident IC impairment was significantly higher in participants with greater SBPV, [HR=1.16 (95 % CI, 1.01-1.33), p = 0.03], while greater DBPV did not show a higher risk of incident IC impairment. CONCLUSIONS: Greater BPV is associated with IC decline over time. Our findings support BP instability as a presumable index of altered cardiovascular homeostatic mechanism, suggesting that BPV might be a clinical marker of aging and addressable risk factor for promoting healthy aging.

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.

Integrative Multimodal Metabolomics to Early Predict Cognitive Decline Among Amyloid Positive Community-Dwelling Older Adults.

Alzheimer's disease is strongly linked to metabolic abnormalities. We aimed to distinguish amyloid-positive people who progressed to cognitive decline from those who remained cognitively intact. We performed untargeted metabolomics of blood samples from amyloid-positive individuals, before any sign of cognitive decline, to distinguish individuals who progressed to cognitive decline from those who remained cognitively intact. A plasma-derived metabolite signature was developed from Supercritical Fluid chromatography coupled with high-resolution mass spectrometry (SFC-HRMS) and nuclear magnetic resonance (NMR) metabolomics. The 2 metabolomics data sets were analyzed by Data Integration Analysis for Biomarker discovery using Latent approaches for Omics studies (DIABLO), to identify a minimum set of metabolites that could describe cognitive decline status. NMR or SFC-HRMS data alone cannot predict cognitive decline. However, among the 320 metabolites identified, a statistical method that integrated the 2 data sets enabled the identification of a minimal signature of 9 metabolites (3-hydroxybutyrate, citrate, succinate, acetone, methionine, glucose, serine, sphingomyelin d18:1/C26:0 and triglyceride C48:3) with a statistically significant ability to predict cognitive decline more than 3 years before decline. This metabolic fingerprint obtained during this exploratory study may help to predict amyloid-positive individuals who will develop cognitive decline. Due to the high prevalence of brain amyloid-positivity in older adults, identifying adults who will have cognitive decline will enable the development of personalized and early interventions.

Nutrition and neurodegeneration: epidemiological evidence and challenges for future research.

The prevention of dementias, such as Alzheimer's disease (AD), is a growing public health concern, due to a lack of effective curative treatment options and a rising global prevalence. Various potential risk or preventive factors have been suggested by epidemiological research, including modifiable lifestyle factors such as diet. Current epidemiological data are in favour of a protective role of certain micronutrients (B vitamins related to homocysteine metabolism, the anti-oxidant vitamins C and E, flavonoids, polyunsatured omega-3 fatty acids, vitamin D) and macronutrients (fish) in the prevention of cognitive decline and dementia/AD. Some factors have been targeted by interventions tested in randomized controlled trials (RCTs), but many of the results are conflicting with observational evidence. Epidemiological analysis of the relations between nutrient consumption and cognitive decline is complex and it is highly unlikely that a single component plays a major role. In addition, since multiple factors across the life course influence brain function in late life, multidomain interventions might be more promising in the prevention of cognitive decline and dementia/AD. Designing such trials remains very challenging for researchers. The main objective of this paper is to review the epidemiologic data linking potential protective factors to cognitive decline or dementia/AD, focusing particularly on the roles of adiposity, caloric restriction, micro (group B vitamins related to homocysteine metabolism, the anti-oxidant vitamins C and E, flavonoids, polyunsatured omega-3 fatty acids, vitamin D) and macronutrients (fish). Limitations of the current data, divergence with results of interventional prevention studies and challenges for future research are discussed.

Weight changes in Alzheimer's disease patients with increased aberrant motor behavior.

OBJECTIVE: Weight loss and behavioral disturbances are frequent over the course of Alzheimer's disease (AD) and are risk factors for poor outcome. We investigated the impact of aberrant motor behavior (AMB) on weight changes in older adults with AD. The hypothesis that patients with AMB are more likely to lose weight than patients without AMB was assessed. METHODS: A prospective study of 686 patients with moderate AD from the REAL.FR cohort was assessed. The AMB at baseline was defined by the item 10 from the Neuropsychiatric Inventory scale (NPI-10). Patients were classified as "no or light AMB" (NPI-10 < 4), and "significant AMB" (NPI-10 ≥ 4). Weight changes were determined over the 4-year follow-up. RESULTS: The mean weight change over the 4 years was +2.2 ± 0.9 kg in patients with "significant AMB," whereas weight remained stable in patients with "no or light AMB" (p = 0.02). CONCLUSION: Older adults with moderate AD and "significant AMB" do gain weight.

Sarcopenia and cognitive impairment in elderly women: results from the EPIDOS cohort.

BACKGROUND: common pathophysiological pathways are shared between age-related body composition changes and cognitive impairment. OBJECTIVE: evaluate whether current operative sarcopenia definitions are associated with cognition in community-dwelling older women. DESIGN: cross-sectional analyses. SUBJECTS: a total of 3,025 women aged 75 years and older. MEASUREMENTS: body composition (assessed by dual energy X-ray absorptiometry) and cognition (measured by short portable mental status questionnaire) were obtained in all participants. Multivariate logistic regression models assessed the association of six operative definitions of sarcopenia with cognitive impairment. Gait speed (GS, measured over a 6-meter track at usual pace) and handgrip strength (HG, measured by a hand-held dynamometer) were considered additional factors of interest. RESULTS: a total of 492 (16.3%) women were cognitively impaired. The prevalence of sarcopenia ranged from 3.3 to 18.8%. No sarcopenia definition was associated with cognitive impairment after controlling for potential confounders. To proof consistency, the analyses were performed using GS and HG, two well-established predictors of cognitive impairment. Low GS [odds ratio (OR) 2.42, 95% confidence interval (CI) 1.72-3.40] and low HG (OR: 1.81, 95% CI: 1.33-2.46) were associated with cognitive impairment. CONCLUSION: no significant association was evidenced between different operative sarcopenia definitions and cognitive impairment. The study suggests that the association between physical performance and cognitive impairment in not mediated by sarcopenia.

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.

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.

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.

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.