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Frailty has been related to inflammaging and certain immune parameters. In previous analyses of participants older than 80 years of age in the longitudinal BELFRAIL cohort study, the main focus was on T-cell phenotypes and the association with cytomegalovirus (CMV) serostatus and survival, finding that a CD4:CD8 ratio greater than 5 was associated with frailty, impaired activities of daily living (ADLs), and mortality (but only in women). Here, we phenotyped peripheral blood immune cells via multicolor flow cytometry and correlated these with the dynamics of changes in ADL, geriatric depression score, Mini-Mental State Examination, and Short Physical Performance Battery from baseline values over 18 months follow-up. We found that higher frequencies of B cells and late-differentiated CD8+ T cells at 18 months from baseline were associated with ADL impairment that had worsened over the preceding 18 months. There were no significant associations with monocyte, dendritic cell, or natural killer (NK) cell phenotypes. No associations with the Geriatric Depression Scale, the Mini-Mental State Examination, or the Short Physical Performance Battery were found. Thus, while these results do not establish causality, they suggest that certain adaptive immune, but not innate immune, parameters are associated with a worsened ADL in the very old., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To examine if the estimated glomerular filtration rate (eGFR) slope over a 5-year period is related to incident cardiovascular (CV) events in the following 5 years., Design: Retrospective cohort study., Setting: Primary care., Participants: All patients aged ≥50 years with at least four eGFR measurements between 01 January 2006 and 31 December 2010 were included in the study., Outcome Measures: During the follow-up period (01 January 2011 until 31 December 2015), CV events (acute myocardial infarction, stroke (cerebrovascular accident (CVA)/transient ischemic attack (TIA)), peripheral arterial disease and acute heart failure) were identified., Methods: The slope was calculated by the least square method (in mL/min/year). The following slope categories were considered: (-1 to 1), (-3 to -1) (-5 to -3), ≤-5, (1 to 3), (3 to 5) and ≥5.00 mL/min/year. Cox proportional hazards model was used to assess the association between eGFR slope and incidence of CV events. Survival probability from CV events was estimated per slope category., Results: 19 567 patients had at least four eGFR measurements, of whom 52% was female. 12% of the ≤-5 slope category developed a new CV event in comparison to 7.8% of the reference group and 5.4% of the ≥5 slope category. Survival rates were worst in those with a slope ≤-5. Patients with a slope of (-5 to -3) and ≤-5 had an adjusted HR of 1.37 and 1.55, respectively. Most patients with a slope <-3 mL/min had an eGFR still >60 mL/min., Conclusions: Negative eGFR slopes of at least 3 mL/min/year give irrespectively of the eGFR itself a higher risk of CV events compared with patient groups with stable or improved kidney function. So the eGFR slope identifies an easy to define group of patients with a high risk for developing CV events., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Forced expiratory volume in 1 s over height cubed (FEV 1 /Ht 3 ) is an FEV 1 expression that uses no reference values and is independently associated with adverse outcomes in older adults. No studies have reported on the prognostic value of its decline over time in adults aged 80 and over., Aim: To investigate the prognostic value of FEV 1 /Ht 3 decline for adverse outcomes in a cohort of adults aged 80 and over., Methods: 328 community-dwelling adults aged 80 and over of the BELFRAIL prospective cohort had two valid FEV 1 measurements as part of their comprehensive geriatric assessment at baseline and follow-up (after 1.7 ± 0.21 years). Kaplan-Meier survival curves, Cox and logistic multivariable regression, assessed association of excessive decline of FEV 1 /Ht 3 (lowest quintile of percentage change) with all-cause mortality (3 years after follow-up assessment), time to first hospitalization (1 year), and new/ worsened disability in activities of daily living (ADL) at the follow-up assessment., Results: Participants with excessive FEV 1 /Ht 3 decline had increased adjusted hazard ratio for all-cause death 1.61 (95% CI 1.01-2.55) and first hospitalization 1.71 (1.08-2.71) and increased odds ratio for new/worsened ADL disability at follow-up 2.02 (1.10-3.68) compared to the rest of the study population., Conclusions: Excessive, short-term decline in FEV 1 /Ht 3 was independently associated with all-cause mortality, time to first, unplanned hospitalization, and ADL disability in a cohort of adults aged 80 and over. This FEV 1 expression should be further investigated in studies of longitudinal FEV 1 change in older adults.

Purpose: We set out to assess whether a high sense of coherence (SOC) protects from adverse health outcomes in patients aged 80 years and older who have multiple chronic diseases., Methods: A population-based prospective cohort study in 29 primary care practices throughout Belgium included 567 individuals aged 80 years and older. We plotted the highest tertile of SOC scores in Kaplan-Meier curves representing 3-year mortality and time to first hospitalization. Using Cox proportional hazard regression analyses and multiple logistic regression analyses adjusted for sociodemographic characteristics, depression, cognition, disability, and multimorbidity we examined the relationship between SOC and mortality, hospitalization, and decline in performance of activities of daily living (ADL)., Results: Subjects with high SOC scores showed a higher cumulative survival than others (Log rank = 0.004) independent of other prognostic characteristics (adjusted hazard ratio 0.62 (95% CI, 0.38-1.00), P = .049). For ADL decline, a high SOC was shown to be protective, and this effect tended to be independent from the covariates under study (adjusted odds ratio 0.56 (95% CI, 0.31-1.0), P = .05)., Conclusion: Even very elderly persons with high SOC scores were shown to have lower mortality rates and less functional decline. These effects were independent of multimorbidity, depression, cognition, disability, and sociodemographic characteristics., (© 2016 Annals of Family Medicine, Inc.)

Background: Certain inflammatory biomarkers increase with age, provide information about general burden of illness and could cause or reflect any collateral damage to healthy cells and organs. However, comparative studies to predict adverse outcomes are missing. Therefore, our study validated and identified the principal prognostic marker to predict important adverse outcomes in the oldest old from an extensive battery of serum inflammatory markers., Methods: A large battery of potential 'inflammaging' markers (IL-1α, IL1-β, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, EGF, VEGF, MCP-1, usCRP, prealbumin) was assessed in a representative sample of 415 heterogenic individuals 80years of age or older in the BELFRAIL study. Kaplan-Meier, Cox proportional hazards and CART analyses determined the overall prognostic value of these markers for predicting all-cause, cardiovascular and non-cardiovascular mortality as well as hospitalization., Results: Serum IL-6 and usCRP levels were strongly associated with time of survival, independent of cause of death. Serum IL-6 levels had the most robust dose-response relationship with mortality. To a lesser extent, IL-10 and IL-1β were associated with all-cause mortality but were restricted to non-cardiovascular or cardiovascular mortality, respectively. Having a low IL-6 at baseline (<1.77pg/ml) could predict 90% of those who were not at risk for all-cause mortality after 3years, even after adjusting for confounders. Similarly, we observed an 83.6% chance of identifying those cases with 0 or 1 hospitalization using low IL-6 serum levels., Conclusion: The results suggest that a single measurement of low IL-6 serum levels is the first choice to guide clinical practice in the oldest old and could summarize the short-term risk of death and hospitalization., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: To examine the relation between static and dynamic blood pressure (BP) measurements and the evolution of kidney function in older people, adjusted for the presence of multimorbidity., Design: Retrospective cohort study during a 10-year time interval (2002-2012) in three age strata of patients aged 60 and older., Setting: Primary care registration network with 97 general practitioners working in 55 practices regularly submitting collected patient data., Participants: All patients with at least one BP measurement in 2002 and at least four serum creatine measurements after 2002 (n=8636). A modified Charlson Comorbidity Index (mCCI) at baseline was registered. Change in systolic and diastolic BP (DBP) and pulse pressure (PP) from 2002 onwards was calculated. The relation between kidney function evolution and baseline BP and change in BP was examined using linear and logistic regression analysis., Main Outcome Measures: The slope of the estimated glomerular filtration rate (eGFR, MDRD, Modification of Diet in Renal Disease equation) was calculated by the ordinal least square method. A rapid annual decline of kidney function was defined as ≥ 3 L/min/1.73 m(2)/year., Results: Rapid annual decline of kidney function occurred in 1130 patients (13.1%). High baseline systolic BP (SBP) and PP predicted kidney function decline in participants aged 60-79 years. No correlation between baseline BP and kidney function decline was found in participants aged 80 years and older. An annual decline of ≥ 1 mm Hg in SBP and PP was a strong risk factor for a rapid annual kidney function decline in all age strata, independent of baseline BP and mCCI. A decline in DBP as also a strong independent predictor in participants aged 60-79 years., Conclusions: The present study identified a decline in BP over time as a strong risk factor for kidney function decline in all age strata, adjusted for mCCI and baseline kidney function and BP., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: previous studies have demonstrated an association between cytomegalovirus (CMV) infection and mortality in adults. In this prospective study, it was investigated whether these findings could be confirmed in the oldest old., Methodology: data obtained from a prospective observational cohort study (2008-2012) of 549 community-dwelling persons in Belgium aged 80 and older., Results: seventy-six percent were anti-CMV seropositive of whom 37.5% had an anti-CMV IgG titre in the highest tertile (>250 IU/ml). After a median time of follow-up of 1,049 days, 127 deaths occurred. Cox proportional hazard models failed to show an association between CMV serostatus and all-cause mortality. Among persons seropositive for CMV, after adjusting for multiple confounders an anti-CMV in the highest tertile was statistically significantly associated with all-cause mortality (hazard ratio: 1.64, 95% confidence interval: 1.08, 2.48)., Conclusion: in contrast to previous findings, a positive CMV serostatus was not associated with an increased risk for all-cause mortality in this cohort of very old people. This is probably the result of a survival effect. CMV seropositive subjects with high anti-CMV titres were at higher risk for all-cause mortality compared with other individuals. This may reflect CMV infection reactivation to be more common in the end stages of life., (© The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The large burden and coexistence of physical disability, cognitive impairment, and depression in the oldest old makes summary markers of global functioning of great value, allowing for risk stratification. Inflammation may be a common underlying cause or represents a final common pathway. The present study investigated the association between elevated serum inflammatory markers and global functioning and its underlying aspects. A representative sample of 415 community-dwelling elderly subjects participating in the BELFRAIL study, with a mean age of 85 years, was included in the present analysis. Data on physical performance, dependence, and mental aspects of functioning and serum levels of 15 inflammatory proteins, including cytokines, chemokines, and acute-phase proteins, were assessed. Interleukin (IL)-6 was negatively associated with global functioning (odds ratio (OR) 4.35). The odds ratios for C-reactive protein (CRP) (OR 2.37) and the combined score of IL-6 and CRP (OR 2.59) were lower or not significant. IL-6 was significantly associated with physical dependence and cognitive function, and only a highly elevated serum level was associated with physical performance. Physical dependence was associated with a highly elevated CRP serum level. The proportion of functionally impaired older persons with elevated IL-6 was 81.93 %, giving a low positive predictive value (0.38), but a high negative predictive value (0.87). So, IL-6 is strongly associated with global functioning and all of the individual aspects of functioning, except suspected depression, in community-dwelling persons 80 years and older.

The chronic inflammatory state at old age may contribute to the pathophysiology of or reflect chronic conditions resulting in loss of physical and mental functioning. Therefore, our objective was to examine the predictive value of a large battery of serum inflammatory markers as risk indicators for global functional decline and its specific physical and mental determinants in the oldest old. Global functional decline and specific aspects of physical and mental functional decline were assessed during an average of 1.66 years (±0.21) in a sample of 303 persons aged 80 years or older of the BELFRAIL study. Serum levels of 14 inflammatory proteins, including cytokines, growth factors, and acute phase proteins, were measured at baseline. Almost 20 % of the participants had a significant global functional decline over time. Interleukin (IL)-6 serum levels were uniquely positively associated with global functional decline, even after correcting for multiple confounders (odds ratio 1.51). Odds ratios for the individual aspects (physical dependency, physical performance, cognition, and depression) of functioning were lower, and composite scores of physical or mental decline were not significant. The proportion of global functional decline exhibited a dose-response curve with increasing levels of IL-6. Thus, IL-6 is an independent risk indicator for accelerated global functional decline in the oldest old. Our results suggest that simple serum levels of IL-6 may be very useful in short-term identification or evaluation of global functional status in the oldest old.

Background: the prevalence of sarcopenia varies widely between studies. The objective of this study was to assess the prevalence of sarcopenia in a representative sample of persons aged 80 years and older according to the European Working Group on Sarcopenia in Older People (EWGSOP) algorithm and the proposed cut-off values. A secondary aim was to investigate the relationship between different individual criteria and low physical performance capacity., Methods: baseline data of the prospective BELFRAIL study (BFC80+) were analysed. Sarcopenia status was determined according to the EWGSOP guidelines. The skeletal muscle mass index (SMI) was assessed according to bioelectrical impedance. Muscle strength and muscle performance were evaluated according to grip strength and the modified short physical performance battery (SPPBm). A logistic regression analysis was performed., Results: according to the EWGSOP algorithm, 12.5% of the participants were classified in the sarcopenia group. Sixty percent of the female participants had muscle strength values below the cut-off and 70% had low SPPBm values. In males, these prevalence values were 49.5% for grip strength and 39.7% for SPPB. The logistic regression analysis showed that low SPPBm was associated with grip strength (OR: 0.88, 95% CI: 0.84-0.92) independent of SMI., Conclusion: in a population-based sample of the very old the prevalence of sarcopenia according to the EWGSOP algorithm is similar to the prevalence of sarcopenia with SMI as a single criterion. A large number of participants with a sufficient SMI value showed low muscle strength and/or a poor SPPBm score. A low SPPBm was associated with grip strength but not with SMI.

Background: vitamin D deficiency is a well-known cause of bone loss and fractures but its association, especially among the oldest old, with muscle weakness is less obvious., Objective: to investigate the relationship between 25-hydroxyvitamin D (25-OHD) and muscle performance in persons aged 80 years and older., Methods: baseline results of the Belfrail study, a prospective, population-based cohort study were used to study balance, grip strength and gait speed in relation to 25-OHD serum levels in 367 subjects., Results: a sufficient 25-OHD serum level of 30 ng/ml or more was found in 12.8% of the population. The prevalence of vitamin deficiency (20-29 ng/ml), insufficiency (10-19 ng/ml) and severe insufficiency (<10 ng/ml) was 21.5, 33 and 32.7%, respectively. No significant relation between balance, gait speed and grip strength, and serum 25-OHD was detected neither in bivariate analysis nor after adjustment for age, gender, level of education, institutionalisation, smoking status, body mass index, co-morbidity, level of activity, season, CRP, renal function, serum calcium parathyroid hormone levels, vitamin D intake and use of loop or thiazide diuretics., Conclusion: in this cohort of octogenarians vitamin D deficiency was highly prevalent. We could not confirm the findings of previous studies showing an association between serum 25-OHD and physical performance in elderly.

Background: In coming decades the proportion of very elderly people living in the Western world will dramatically increase. This forthcoming "grey epidemic" will lead to an explosion of chronic diseases. In order to anticipate booming health care expenditures and to assure that social security is funded in the future, research focusing on the relationship between chronic diseases, frailty and disability is needed. The general aim of the BELFRAIL cohort study (BFC80+) is to study the dynamic interaction between health, frailty and disability in a multi-system approach focusing on cardiac dysfunction and chronic heart failure, lung function, sarcopenia, renal insufficiency and immunosenescence., Methods/design: The BFC80+ is a prospective, observational, population-based cohort study of subjects aged 80 years and older in three well-circumscribed areas of Belgium. In total, 29 general practitioner (GP) centres were asked to include patients aged 80 and older. Only three exclusion criteria were used: severe dementia, in palliative care and medical emergency. Two sampling methods for the recruitment of patients were used. Between November 2, 2008 and September 15, 2009, 567 subjects were included in the BFC80+ study. Every study participant was invited to undergo four study visits. The GP recorded background variables and medical history and performed a detailed anamnesis and clinical examination. The clinical research assistant performed an extensive examination including performance testing, questionnaires and technical examinations. Echocardiography was performed at home by a cardiologist. A blood sample was collected in the morning. Follow-up reporting of hard outcome measures including mortality, hospitalization and morbidity was organized. A second data collection is planned after 18 months., Discussion: The BFC80+ was designed to acquire a better understanding of the epidemiology and pathophysiology of chronic diseases in the very elderly and to study the dynamic interaction between health, frailty and disability in a multi-system approach. The wide variety of dimensions investigated in the BFC80+ will enable us not only to investigate in depth the relationship between the different physiological systems but also to initiate new research questions based on this unique database of community-dwelling elderly.