Circadian disturbances and frailty risk in older adults.
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ABSTRACT:
SUBMITTER: Cai R
PROVIDER: S-EPMC10654720 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
Publications
Circadian disturbances and frailty risk in older adults.
Cai Ruixue R Gao Lei L Gao Chenlu C Yu Lei L Zheng Xi X Bennett David A DA Buchman Aron S AS Hu Kun K Li Peng P
Nature communications 20231116 1
Frailty is characterized by diminished resilience to stressor events. It is associated with adverse future health outcomes and impedes healthy aging. The circadian system orchestrates ~24-h rhythms in bodily functions in synchrony with the day-night cycle, and disturbed circadian regulation plays an important role in many age-related health consequences. We investigated prospective associations of circadian disturbances with incident frailty in over 1000 older adults who had been followed annual ...[more]
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Project description:ObjectiveTo test the hypothesis that non-frail older men with poorer sleep at baseline are at increased risk of frailty and death at follow-up.MethodsIn this prospective cohort study, subjective (questionnaires) and objective sleep parameters (actigraphy, in-home overnight polysomnography) were measured at baseline in 2505 non-frail men aged ≥67years. Repeat frailty status assessment performed an average of 3.4 years later; vital status assessed every four months. Sleep parameters expressed as dichotomized predictors using clinical cut-points. Status at follow-up exam classified as robust, intermediate (pre-frail) stage, frail, or died in interim.ResultsNone of the sleep disturbances were associated with the odds of being intermediate/frail/dead (vs. robust) at follow-up. Poor subjective sleep quality (multivariable odds ratio [MOR] 1.26, 95% CI 1.01-1.58), greater nighttime wakefulness (MOR 1.31, 95% CI 1.04-1.66), and greater nocturnal hypoxemia (MOR 1.47, 95% CI 1.02-2.10) were associated with a higher odds of frailty/death at follow-up (vs. robust/intermediate). Excessive daytime sleepiness (MOR 1.60, 95% CI 1.03-2.47), greater nighttime wakefulness (MOR 1.57, 95% CI 1.12-2.20), severe sleep apnea (MOR 1.74, 95% CI 1.04-2.89), and nocturnal hypoxemia (MOR 2.28, 95% CI 1.45-3.58) were associated with higher odds of death (vs. robust/intermediate/frail at follow-up). The association between poor sleep efficiency and mortality nearly reached significance (MOR 1.48, 95% CI 0.99-2.22). Short sleep duration and prolonged sleep latency were not associated with frailty/death or death at follow-up.ConclusionsAmong non-frail older men, poor subjective sleep quality, greater nighttime wakefulness, and greater nocturnal hypoxemia were independently associated with higher odds of frailty or death at follow-up, while excessive daytime sleepiness, greater nighttime wakefulness, severe sleep apnea and greater nocturnal hypoxemia were independently associated with an increased risk of mortality.
| S-EPMC3449012 | biostudies-literature
Project description:BackgroundThe integral part of the definition of frailty is the outcome associated with it. Older adults at risk of frailty are in the process of becoming frail. This study looked at the clinical characteristics and outcomes of older adults at risk of frailty.MethodologyThe study population was selected from outpatient department of the geriatric medicine department in a tertiary care hospital. Older adults identified as at risk of frailty were assessed at baseline and then followed up after 1 year for the composite primary outcome of death, falls, hospitalization, and self-rated poor quality of life in the follow-up period.ResultsThe study included 324 older adults who had completed 1-year follow up. Mean (SD) age was 74.49 (4.58) years, and males were 241 (74.15%). Frail and pre-frail at baseline among the study population were 31.17% and 61.11%, respectively. The primary outcome occurred in 43 (13.27%) patients. Poor baseline IADL was significantly associated with primary outcome at the end of 1 year.ConclusionAn unfavorable outcome in older adults at risk of frailty was significantly higher and independent of their baseline frailty status. Poor baseline IADL value may be considered as a predictor for primary outcome at 1 year of follow up.
| S-EPMC8711216 | biostudies-literature
Project description:BackgroundCircadian disturbances are commonly seen in people with Alzheimer's disease and have been reported in individuals without symptoms of dementia but with Alzheimer's pathology. We aimed to assess the temporal relationship between circadian disturbances and Alzheimer's progression.MethodsWe did a prospective cohort study of 1401 healthy older adults (aged >59 years) enrolled in the Rush Memory and Aging Project (Rush University Medical Center, Chicago, IL, USA) who had been followed up for up to 15 years. Participants underwent annual assessments of cognition (with a battery of 21 cognitive performance tests) and motor activities (with actigraphy). Four measures were extracted from actigraphy to quantify daily and circadian rhythmicity, which were amplitude of 24-h activity rhythm, acrophase (representing peak activity time), interdaily stability of 24-h activity rhythm, and intradaily variability for hourly fragmentation of activity rhythm. We used Cox proportional hazards models and logistic regressions to assess whether circadian disturbances predict an increased risk of incident Alzheimer's dementia and conversion of mild cognitive impairment to Alzheimer's dementia. We used linear mixed-effects models to investigate how circadian rhythms changed longitudinally and how the change integrated to Alzheimer's progression.FindingsParticipants had a median age of 81·8 (IQR 76·3-85·7) years. Risk of developing Alzheimer's dementia was increased with lower amplitude (1 SD decrease, hazard ratio [HR] 1·39, 95% CI 1·19-1·62) and higher intradaily variability (1 SD increase, 1·22, 1·04-1·43). In participants with mild cognitive impairment, increased risk of Alzheimer's dementia was predicted by lower amplitude (1 SD decrease, HR 1·46, 95% CI 1·24-1·72), higher intradaily variability (1 SD increase, 1·36, 1·15-1·60), and lower interdaily stability (1 SD decrease, 1·21, 1·02-1·44). A faster transition to Alzheimer's dementia in participants with mild cognitive impairment was predicted by lower amplitude (1 SD decrease, odds ratio [OR] 2·08, 95% CI 1·53-2·93), increased intradaily variability (1 SD increase, 1·97, 1·43-2·79), and decreased interdaily stability (1 SD decrease, 1·35, 1·01-1·84). Circadian amplitude, acrophase, and interdaily stability progressively decreased over time, and intradaily variability progressively increased over time. Alzheimer's progression accelerated these aging effects by doubling or more than doubling the annual changes in these measures after the diagnosis of mild cognitive impairment, and further doubled them after the diagnosis of Alzheimer's dementia. The longitudinal change of global cognition positively correlated with the longitudinal changes in amplitude and interdaily stability and negatively correlated with the longitudinal change in intradaily variability.InterpretationOur results indicate a link between circadian dysregulation and Alzheimer's progression, implying either a bidirectional relation or shared common underlying pathophysiological mechanisms.FundingNational Institutes of Health, and the BrightFocus Foundation.
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Project description:Physical frailty's impact on hemagglutination inhibition antibody titers (HAI) and peripheral blood mononuclear cell (PBMC) transcriptional responses after influenza vaccination is unclear. Physical frailty was assessed using the 5-item Fried frailty phenotype in 168 community- and assisted-living adults ≥55 years of age during an observational study. Blood was drawn before, 3, 7, and 28 days post-vaccination with the 2017-2018 inactivated influenza vaccine. HAI response to the A/H1N1 strain was measured at Days 0 and 28 using seropositivity, seroconversion, log2 HAI titers, and fold-rise in log2 HAI titers. RNA sequencing of PBMCs from Days 0, 3 and 7 was measured in 28 participants and compared using pathway analyses. Frailty was not significantly associated with any HAI outcome in multivariable models. Compared with non-frail participants, frail participants expressed decreased cell proliferation, metabolism, antibody production, and interferon signaling genes. Conversely, frail participants showed elevated gene expression in IL-8 signaling, T-cell exhaustion, and oxidative stress pathways compared with non-frail participants. These results suggest that reduced effectiveness of influenza vaccine among older, frail individuals may be attributed to immunosenescence-related changes in PBMCs that are not reflected in antibody levels.
2022-02-16 | GSE196793 | GEO
Project description:This study examines whether frailty is associated with mortality independently of physiological dysregulation (PD) and, if so, which is the more accurate predictor of survival. Data come from the Social Environment and Biomarkers of Aging Study. We use Cox proportional hazard models to test the associations between PD, frailty, and 4- to 5-year survival. We use Harrell's concordance index to compare predictive accuracy of the models. Both PD and frailty are significantly, positively, and independently correlated with mortality: Worse PD scores and being frail are associated with a higher risk of dying. The overall PD score is a more accurate predictor of survival than frailty, although model prediction improves when both measures are included. PD and frailty independently predict mortality, suggesting that the two measures may be capturing different aspects of the same construct and that both may be important for identifying individuals at risk for adverse health outcomes.
| S-EPMC5507735 | biostudies-literature
Project description:Factors associated with frailty, particularly dietary patterns, are not fully understood in Mediterranean countries. This study aimed to investigate the association of data-driven dietary patterns with frailty prevalence in older Lebanese adults. We conducted a cross-sectional national study that included 352 participants above 60 years of age. Sociodemographic and health-related data were collected. Food frequency questionnaires were used to elaborate dietary patterns via the K-mean cluster analysis method. Frailty that accounted for 15% of the sample was twice as much in women (20%) than men (10%). Identified dietary patterns included a Westernized-type dietary pattern (WDP), a high intake/Mediterranean-type dietary pattern (HI-MEDDP), and a moderate intake/Mediterranean-type dietary pattern (MOD-MEDDP). In the multivariate analysis, age, waist to height ratio, polypharmacy, age-related conditions, and WDP were independently associated with frailty. In comparison to MOD-MEDDP, and after adjusting for covariates, adopting a WDP was strongly associated with a higher frailty prevalence in men (OR = 6.63, 95% (CI) (1.82-24.21) and in women (OR = 11.54, 95% (CI) (2.02-65.85). In conclusion, MOD-MEDDP was associated with the least prevalence of frailty, and WDP had the strongest association with frailty in this sample. In the Mediterranean sample, a diet far from the traditional one appears as the key deleterious determinant of frailty.
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Project description:ObjectiveTo identify salient characteristics of frailty that increase risk of death in depressed elders.MethodsData were from the Nordic Research on Ageing Study from research sites in Denmark, Sweden, and Finland. Participants were 1,027 adults aged 75 years (436 men and 591 women). Time of death was obtained, providing a maximum survival time of 11.08 years (initial evaluation took place between 1988 and 1991).ResultsDepressed elders showed greater baseline impairments in each frailty characteristic (gait speed, grip strength, physical activity levels, and fatigue). Simultaneous models including all four frailty characteristics showed slow gait speed (hazard ratio: 1.84; 95% confidence interval: 1.05-3.21) and fatigue (hazard ratio: 1.94; 95% confidence interval: 1.11-3.40) associated with faster progression to death in depressed women; none of the frailty characteristics in the simultaneous model was associated with death in depressed men. In women, the effect of impaired gait speed on mortality rates nearly doubled when depression was present (nondepressed women: no gait impairment = 26%; slow gait = 40%; depressed women: no gait impairment = 32%; slow gait = 58%). A similar pattern was observed for fatigue.ConclusionThe confluence of specific characteristics of frailty (fatigue and slow gait speed) and depressive illness is associated with an increased risk of death in older adults; this association is particularly strong in older depressed women. Future research should investigate whether multimodal interventions targeting depressive illness, mobility deficits, and fatigue can decrease mortality and improve quality of life in older depressed individuals with characteristics of the syndrome of frailty.
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Project description:IntroductionIn healthy older adults, the relationship between long-term, visit-to-visit variability in blood pressure (BP) and frailty is uncertain.MethodsSecondary analysis of blood pressure variability (BPV) and incident frailty in >13 000 participants ≥65-70 years enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) trial and its observational follow-up (ASPREE-XT). Participants were without dementia, physical disability, or cardiovascular disease at baseline. BPV was estimated using standard deviation of mean BP from three annual visits (baseline through the second annual follow-up). Frailty was defined using Fried phenotype and a frailty deficit accumulation index (FDAI). Participants with frailty during the BPV estimation period were excluded from the main analysis. Adjusted Cox proportional hazards regression evaluated the association between BPV and incident frailty, and linear mixed models for change in frailty scores, through a maximum of 9 years of follow-up.ResultsParticipants in the highest systolic BPV tertile were at higher risk of frailty compared to those in the lowest (referent) tertile of systolic BPV [Fried hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.04-1.31; FDAI HR 1.18, 95% CI 1.07-1.30]. Findings were consistent when adjusted for multiple covariates and when stratified by antihypertensive use. Linear mixed models showed that higher systolic BPV was associated with increasing frailty score over time. Diastolic BPV was not consistently associated.ConclusionsHigh systolic BPV, independent of mean BP, is associated with increased risk of frailty in healthy older adults. Variability of BP across visits, even in healthy older adults, can convey important risk information beyond mean BP.Trial registrationClinicalTrials.gov NCT01038583 and ISRCTN83772183.
| S-EPMC10842997 | biostudies-literature
Project description:Frailty is a state of late life decline and vulnerability, typified by physical weakness and decreased physiologic reserve. The epidemiology and pathophysiology of frailty share features with those of cardiovascular disease. Gait speed can be used as a measure of frailty and is a powerful predictor of mortality. Advancing age is a potent risk factor for cardiovascular disease and has been associated with an increased risk of adverse outcomes. Older adults comprise approximately half of cardiac surgery patients, and account for nearly 80% of the major complications and deaths following surgery. The ability of traditional risk models to predict mortality and major morbidity in older patients being considered for cardiac surgery may improve if frailty, as measured by gait speed, is included in their assessment. It is possible that in the future frailty assessment may assist in choosing among therapies (e.g., surgical vs. percutaneous aortic valve replacement for patients with aortic stenosis).
| S-EPMC4308458 | biostudies-other