The long-term clinical and physiological consequences of COVID-19 infection remain unclear. While fatigue has emerged as a common symptom following infection, little is known about its links with ...autonomic dysfunction. SARS-CoV-2 is known to infect endothelial cells in acute infection, resulting in autonomic dysfunction. Here we set out to test the hypothesis that this results in persistent autonomic dysfunction and is associated with post-COVID fatigue in convalescent patients.
We recruited 20 fatigued and 20 non-fatigued post-COVID patients (median age 44.5 years, 36/40 (90%) female, median time to follow up 166.5 days). Fatigue was assessed using the Chalder Fatigue Scale. These underwent the Ewing's autonomic function test battery, including deep breathing, active standing, Valsalva manoeuvre and cold-pressor testing, with continuous electrocardiogram and blood pressure monitoring, as well as near-infrared spectroscopy-based cerebral oxygenation. 24-hour ambulatory blood pressure monitoring was also conducted, and patients completed the generalised anxiety disorder-7 questionnaire. We assessed between-group differences in autonomic function test results and used unadjusted and adjusted linear regression to investigate the relationship between fatigue, anxiety, and autonomic test results.
We found no pathological differences between fatigued and non-fatigued patients on autonomic testing or on 24-hour blood pressure monitoring. Symptoms of orthostatic intolerance were reported by 70% of the fatigued cohort at the time of active standing, with no associated physiological abnormality detected. Fatigue was strongly associated with increased anxiety (p <0.001), with no patients having a pre-existing diagnosis of anxiety.
These results demonstrate the significant burden of fatigue, symptoms of autonomic dysfunction and anxiety in the aftermath of COVID-19 infection, but reassuringly do not demonstrate pathological findings on autonomic testing.
Objectives
To explore the relationship between cognitive function and frailty.
Design
A cross‐sectional study using data from Wave 1 of The Irish Longitudinal Study on Ageing, a population ...representative study of adults aged 50 and older in the Republic of Ireland.
Setting
Community‐dwelling adults completed a home‐ or health center–based nurse‐led assessment.
Participants
Individuals aged 50 and older without a history of stroke, Parkinson's disease, or severe cognitive impairment (Mini‐Mental State Examination (MMSE) score <18) and not taking antidepressants (N = 4,649).
Measurements
A cognitive battery including MMSE, Montreal Cognitive Assessment, Color Trails Test, Cambridge Mental Disorders of the Elderly Examination memory and executive function subtests, 10‐word recall, Sustained Attention to Response Task, and choice reaction time was used to generate composite scores of cognitive domains. Frailty was assessed according to weakness, slowness, exhaustion, low physical activity, and weight loss.
Results
After full adjustment, cognitive function across all domains except self‐rated memory and processing speed was significantly worse in prefrail and frail participants (P < .05) than in those who were robust. Weakness and walking speed were most consistently linked to poorer cognition, whereas low activity and weight loss were not independently associated with any cognitive domain. Exhaustion was associated with global cognition (B = −0.18 ± 0.06), with some evidence of links to objectively measured and self‐rated memory.
Conclusion
Cognitive function is worse across multiple cognitive domains in prefrail and frail individuals aged 50 and older than in those who are robust, although the absolute differences are small after adjusting for confounding factors.
Abstract
Background
Social distancing and similar measures in response to the coronavirus disease 2019 pandemic have greatly increased loneliness and social isolation among older adults. ...Understanding the association between loneliness and mortality is therefore critically important. We examined whether combinations of loneliness and social isolation, using a metric named social asymmetry, was associated with increased mortality risk.
Methods
The sample was derived from participants in The Irish Longitudinal Study on Ageing, a nationally representative sample of community-dwelling older adults aged ≥50. Survey data were linked to official death registration records. Cox proportional hazards regressions and competing risk survival analyses were used to examine the association between social asymmetry and all-cause and cause-specific mortality.
Results
Of four social asymmetry groups, concordant low lonely (low loneliness, low isolation) included 35.5% of participants; 26.4% were concordant high lonely (high loneliness, high isolation); 19.2% were discordant robust (low loneliness, high isolation) and 18.9% discordant susceptible (high loneliness, low isolation). The concordant high lonely (hazard ratio HR = 1.43, 95% confidence interval CI: 1.09–1.87) and discordant robust (HR = 1.37, 95% CI: 1.04–1.81) groups had an increased mortality risk compared to those in the concordant low lonely group. The concordant high lonely group had an increased risk of mortality due to diseases of the circulatory system (sub-distribution hazard ratio = 1.52, 95% CI: 1.03–2.25).
Conclusion
We found that social asymmetry predicted mortality over a 7-year follow-up period. Our results confirm that a mismatch between subjective loneliness and objective social isolation, as well as the combination of loneliness and social isolation, were associated with an increased all-cause mortality risk.
Highlights • Frailty may be a marker for future cognitive impairment. • Executive function is the cognitive domain most strongly associated with frailty. • Frailty and cognition interact within a ...cycle of age-associated decline. • AD pathology, cardiovascular risk, depression, and others, are potential mediators. • Our new model outlines the interactions between these hypothesised causal mechanisms.
Abstract
The aging process is characterized by the presence of high interindividual variation between individuals of the same chronical age prompting a search for biomarkers that capture this ...heterogeneity. Epigenetic clocks measure changes in DNA methylation levels at specific CpG sites that are highly correlated with calendar age. The discrepancy resulting from the regression of DNA methylation age on calendar age is hypothesized to represent a measure of biological aging with a positive/negative residual signifying age acceleration (AA)/deceleration, respectively. The present study examines the associations of 4 epigenetic clocks—Horvath, Hannum, PhenoAge, GrimAge—with a wide range of clinical phenotypes (walking speed, grip strength, Fried frailty, polypharmacy, Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MOCA), Sustained Attention Reaction Time, 2-choice reaction time), and with all-cause mortality at up to 10-year follow-up, in a sample of 490 participants in the Irish Longitudinal Study on Ageing (TILDA). HorvathAA and HannumAA were not predictive of health; PhenoAgeAA was associated with 4/9 outcomes (walking speed, frailty MOCA, MMSE) in minimally adjusted models, but not when adjusted for other social and lifestyle factors. GrimAgeAA by contrast was associated with 8/9 outcomes (all except grip strength) in minimally adjusted models, and remained a significant predictor of walking speed, .polypharmacy, frailty, and mortality in fully adjusted models. Results indicate that the GrimAge clock represents a step-improvement in the predictive utility of the epigenetic clocks for identifying age-related decline in an array of clinical phenotypes promising to advance precision medicine.
The thalamus is a central hub of the autonomic network and thalamic volume has been associated with high‐risk phenotypes for sudden cardiac death. Heart rate response to physiological stressors ...(e.g., standing) and the associated recovery patterns provide reliable indicators of both autonomic function and cardiovascular risk. Here we examine if thalamic volume may be a risk marker for impaired heart rate recovery in response to orthostatic challenge. The Irish Longitudinal Study on Aging involves a nationally representative sample of older individuals aged ≥50 years. Multimodal brain magnetic resonance imaging and orthostatic heart rate recovery were available for a cross‐sectional sample of 430 participants. Multivariable regression and linear mixed‐effects models were adjusted for head size, age, sex, education, body mass index, blood pressure, history of cardiovascular diseases and events, cardiovascular medication, diabetes mellitus, smoking, alcohol intake, timed up‐and‐go (a measure of physical frailty), physical exercise and depression. Smaller thalamic volume was associated with slower heart rate recovery (−1.4 bpm per 1 cm3 thalamic volume, 95% CI −2.01 to −0.82; p < .001). In multivariable analysis, participants with smaller thalamic volumes had a mean heart rate recovery −2.7 bpm slower than participants with larger thalamic volumes (95% CI −3.89 to −1.61; p < .001). Covariates associated with smaller thalamic volume included age, history of diabetes, and heavy alcohol consumption. Thalamic volume may be an indicator of the structural integrity of the central autonomic network. It may be a clinical biomarker for stratification of individuals at risk of autonomic dysfunction, cardiovascular events, and sudden cardiac death.
International evidence shows that people approaching end of life (EOL) have high prevalence of polypharmacy, including overprescribing. Overprescribing may have adverse side effects for mental and ...physical health and represents wasteful spending. Little is known about prescribing near EOL in Ireland. We aimed to describe the prevalence of two undesirable outcomes, and to identify factors associated with these outcomes: potentially questionable prescribing, and potentially inadequate prescribing, in the last year of life (LYOL). We used The Irish Longitudinal Study on Ageing, a biennial nationally representative dataset on people aged 50+ in Ireland. We analysed a sub-sample of participants with high mortality risk and categorised their self-reported medication use as potentially questionable or potentially inadequate based on previous research. We identified mortality through the national death registry (died in <365 days versus not). We used descriptive statistics to quantify prevalence of our outcomes, and we used multivariable logistic regression to identify factors associated with these outcomes. Of 525 observations, 401 (76%) had potentially inadequate and 294 (56%) potentially questionable medications. Of the 401 participants with potentially inadequate medications, 42 were in their LYOL. OF the 294 participants with potentially questionable medications, 26 were in their LYOL. One factor was significantly associated with potentially inadequate medications in LYOL: male (odds ratio (OR) 4.40, p = .004) Three factors were associated with potentially questionable medications in LYOL: male (OR 3.37, p = .002); three or more activities of daily living (ADLs) (OR 3.97, p = .003); and outpatient hospital visits (OR 1.03, p = .02). Thousands of older people die annually in Ireland with potentially inappropriate or questionable prescribing patterns. Gender differences for these outcomes are very large. Further work is needed to identify and reduce overprescribing near EOL in Ireland, particularly among men.
Multimorbidity (the presence of multiple medical conditions) is well known to increase with age. People with multimorbidities often have higher physical and functional decline as well as increased ...mortality. Despite growing evidence that integrated and collaborative care improves many undesirable outcomes of multimorbidity, the majority of health systems are based around treating individual diseases. A pattern analysis of comorbidities using network graphs and a novel use of association rules was conducted to investigate disease associations on 6101 Irish adults aged 50+. The complex network of morbidities and differences in the prevalence and interactions of these morbidities by sex was also assessed. Gender specific differences in disease prevalence was found for 22/31 medical conditions included in this study. Females had a more complex network of disease associations than males with strong associations found between arthritis, osteoporosis and thyroid issues among others. To assess the strength of these associations we provide probabilities of being diagnosed with a comorbid condition given the presence of an index morbidity for 639 pairwise combinations. This information can be used to guide clinicians in deciding which comorbidities should be incorporated into comprehensive assessments in addition to anticipating likely future morbidities and thus developing prevention strategies.
Self-reported measures of healthcare utilisation are often used in longitudinal cohort studies involving older community-dwelling people. The aim of this study is to compare healthcare utilisation ...rates using patient self-report and manual extraction from the general practice (GP) electronic medical record (EMR).
Study population: Two prospective cohort studies (n = 806 and n = 1,377, aged ≥70 years) conducted in the Republic of Ireland were compared. Study outcomes: GP, outpatient department (OPD) and emergency department (ED) visits over a one-year period. Statistical analysis: Descriptive statistics of the two cohorts are presented. A negative binomial regression was performed and results are presented as incidence rate ratios (IRR) with 95% confidence intervals (CI). For the outcome of any ED visit, linear regression was performed, yielding risk ratios (RR) with 95% CI.
The annual rates of GP, OPD and ED visits were 6.30 (SD 4.63), 2.11 (SD 2.46) and 0.26 (SD 0.62) respectively in GP EMR cohort, compared to 5.65 (SD 8.06), 2.09 (SD 5.83) and 0.32 (SD 0.84) in the self-report cohort. In univariate regression analysis comparing healthcare utilisation, the self-report cohort reported a lower frequency of GP visits (unadjusted IRR 0.90 (95% CI 0.84, 0.96), p = 0.02)), a greater frequency of ED visits (1.20 (0.98, 1.49), p = 0.083)), and no difference in OPD visits (unadjusted IRR 0.99 (95% CI 0.86, 1.13), p = 0.845)). In multivariate analysis, adjusted for relevant confounders, there was no difference in GP visits (adjusted IRR 0.99 (95% CI 0.92, 1.06), p = 0.684)) or OPD visits (adjusted IRR 1.09 (0.95, 1.25), p = 0.23)) between the two cohorts. However, the self-report cohort reported 37% more ED visits (adjusted IRR 1.37 (1.10, 1.71), p = 0.005)) and were more likely to report any ED visit (adjusted RR 1.23 (95% CI 1.02, 1.48), p = 0.028)).
This study demonstrates that reported rates of GP and OPD visits were similar but there were differences in reported ED visits, with significantly higher self-reported visits. This may be due to ED visits not being notified to the GP and contextual issues such as transfer of healthcare utilisation data between sectors may vary in different healthcare systems.
Abstract Objectives To compare the ability of Timed Up and Go (TUG) and usual gait speed (UGS) to predict incident disability completing basic activities of daily living (ADL) and instrumental ADL ...(IADL) in older adults free of disability at baseline, and to provide estimates for the probability of incident disability at different levels of baseline mobility performance. Design Data from the first 2 waves of The Irish Longitudinal Study on Ageing, a study assessing health, economic, and social aspects of ageing in adults aged ≥50 years. Setting A nationally representative, population-based sample of community-dwelling adults. Participants Participants aged ≥65 years who completed mobility tests during a health assessment, had no reported difficulty in ADL/IADL, and had a Mini-Mental State Examination score ≥24 were re-interviewed after 2 years (n=1664). Interventions Not applicable. Main Outcome Measures Participants completed the TUG and UGS at baseline and indicated difficulty in a number of basic ADL and IADL at follow-up. Results Receiver operating characteristic analysis indicated that TUG and UGS are acceptable tools to predict disability in ADL and IADL (area under the curve AUC=.65–.75) with no significant difference between them ( P >.05). Both were excellent predictors of difficulty in higher-level functioning tasks such as preparing hot meals, taking medications, and managing money (AUC>.80). Predictive probabilities were obtained across a range of performance levels. Conclusions TUG and UGS have similar predictive ability in relation to incident disability in basic ADL and IADL. Predictive probabilities can be used to identify those most at risk and in need of particular services. Since improving physical function can prevent or delay dependence in ADL/IADL, TUG and UGS can also provide performance goals and feedback during exercise interventions.
PDF
