Cardiovascular Autonomic Function and Progression of Age-Related Macular Degeneration in The Irish Longitudinal Study of Ageing (TILDA).

Purpose: To examine if changes in hemodynamic measures during an orthostatic challenge were associated with progression of age-related macular degeneration (AMD) over a 4-year period in The Irish Longitudinal Study on Ageing. Methods: Participants with AMD who underwent an active stand (AS) test at wave 1 (2009/2010) and retinal photographs at both wave 1 and wave 3 (2014/2015) were included (N = 159: 121 with no AMD progression and 38 with progression). Beat-to-beat hemodynamic data were non-invasively collected using a Finometer MIDI device during the AS at wave 1, recording systolic blood pressure (sBP), diastolic blood pressure (dBP), mean arterial pressure (MAP), and heart rate. Cardiac output, stroke volume, and total peripheral resistance (TPR) were derived from these measures. Baseline characteristics were compared between groups with and without AMD progression. Mixed-effects linear regression models were used to assess the association between changes in hemodynamic parameters during the AS and AMD progression, controlling for known AMD-associated risk factors. Results: At baseline, increasing age and lower dBP were significantly associated with AMD progression. Mixed-effects models for the period between standing and 10 seconds post-stand revealed significant associations with AMD progression with a steeper drop in dBP and a slower drop in TPR. Between 10 and 20 seconds post-stand, AMD progression was significantly associated with less pronounced reduction in heart rate. Conclusions: These observational data suggest that impaired hemodynamic responses within the first 20 seconds of orthostasis may be associated with the progression of AMD.

The SHARE Frailty Instrument for Primary Care was Associated with Sarcopenia, as Measured by Bioelectrical Impedance, in Falls Clinic Attendees.

Objective: This study aimed to assess the association between measures of frailty phenotype (FP) and malnutrition, and sarcopenia measured by bioelectrical impedance analysis (BIA), in individuals aged 50 and above attending an outpatient falls clinic. Methods: The Survey of Health, Ageing and Retirement in Europe Frailty Instrument (SHARE-FI) gauged FP status, while nutritional assessment relied on the Mini Nutritional Assessment-Short Form (MNA®-SF). Body composition, specifically appendicular skeletal muscle mass (ASMM), was determined through TANITA® DC-430MA BIA. Multivariable binary logistic regression models were used to predict pre-frailty or frailty based on SHARE-FI and at-risk of malnutrition or malnutrition based on MNA®-SF. Results: Out of the 123 participants (68 women, 55 men), 56.1% were classified as robust, 27.6% as living with pre-frailty, and 16.3% as living with frailty according to SHARE-FI. MNA®-SF results were available for 116 patients, with 54.3% categorised as normal, 39.7% at risk of malnutrition, and 6.0% as malnourished. Among the 118 patients who underwent BIA, ASMM was independently associated with pre-frail/frail status, but there was no significant association between abnormal MNA®-SF and sarcopenia. Conclusion: SHARE-FI, a modified FP tool, demonstrated an independent association with sarcopenia as measured by BIA.

Were Frailty Identification Criteria Created Equal? A Comparative Case Study on Continuous Non-Invasively Collected Neurocardiovascular Signals during an Active Standing Test in the Irish Longitudinal Study on Ageing (TILDA).

BACKGROUND: In this observational study, we compared continuous physiological signals during an active standing test in adults aged 50 years and over, characterised as frail by three different criteria, using data from The Irish Longitudinal Study on Ageing (TILDA). METHODS: This study utilised data from TILDA, an ongoing landmark prospective cohort study of community-dwelling adults aged 50 years or older in Ireland. The initial sampling strategy in TILDA was based on random geodirectory sampling. Four independent groups were identified: those characterised as frail only by one of the frailty tools used (the physical Frailty Phenotype (FP), the 32-item Frailty Index (FI), or the Clinical Frailty Scale (CFS) classification tree), and a fourth group where participants were not characterised as frail by any of these tools. Continuous non-invasive physiological signals were collected during an active standing test, including systolic (sBP) and diastolic (dBP) blood pressure, as well as heart rate (HR), using digital artery photoplethysmography. Additionally, the frontal lobe cerebral oxygenation (Oxy), deoxygenation (Deoxy), and tissue saturation index (TSI) were also non-invasively measured using near-infrared spectroscopy (NIRS). The signals were visualised across frailty groups and statistically compared using one-dimensional statistical parametric mapping (SPM). RESULTS: A total of 1124 participants (mean age of 63.5 years; 50.2% women) were included: 23 were characterised as frail only by the FP, 97 by the FI, 38 by the CFS, and 966 by none of these criteria. The SPM analyses revealed that only the group characterised as frail by the FI had significantly different signals (p < 0.001) compared to the non-frail group. Specifically, they exhibited an attenuated gain in HR between 10 and 15 s post-stand and larger deficits in sBP and dBP between 15 and 20 s post-stand. CONCLUSIONS: The FI proved to be more adept at capturing distinct physiological responses to standing, likely due to its direct inclusion of cardiovascular morbidities in its definition. Significant differences were observed in the dynamics of cardiovascular signals among the frail populations identified by different frailty criteria, suggesting that caution should be taken when employing frailty identification tools on physiological signals, particularly the neurocardiovascular signals in an active standing test.

Evaluation of a 3-Item Health Index in Predicting Mortality Risk: A 12-Year Follow-Up Study.

This study was carried out using a large cohort (N = 4265; 416 deceased) of older, community-dwelling adults from The Irish Longitudinal Study on Ageing (TILDA). The study compared the performance of a new 3-item health index (HI) with two existing measures, the 32-item frailty index (FI) and the frailty phenotype (FP), in predicting mortality risk. The HI was based on the objective measurement of resting-state systolic blood pressure sample entropy, sustained attention reaction time performance, and usual gait speed. Mortality data from a 12-year follow up period were analyzed using Cox proportional regression. All data processing was performed using MATLAB and statistical analysis using STATA 15.1. The HI showed good discriminatory power (AUC = 0.68) for all-cause mortality, similar to FI (AUC = 0.68) and superior to FP (AUC = 0.60). The HI classified participants into Low-Risk (84%), Medium-Risk (15%), and High-Risk (1%) groups, with the High-Risk group showing a significant hazard ratio (HR) of 5.91 in the unadjusted model and 2.06 in the fully adjusted model. The HI also exhibited superior predictive performance for cardiovascular and respiratory deaths (AUC = 0.74), compared with FI (AUC = 0.70) and FP (AUC = 0.64). The HI High-Risk group had the highest HR (15.10 in the unadjusted and 5.61 in the fully adjusted models) for cardiovascular and respiratory mortality. The HI remained a significant predictor of mortality even after comprehensively adjusting for confounding variables. These findings demonstrate the effectiveness of the 3-item HI in predicting 12-year mortality risk across different causes of death. The HI performed similarly to FI and FP for all-cause mortality but outperformed them in predicting cardiovascular and respiratory deaths. Its ability to classify individuals into risk groups offers a practical approach for clinicians and researchers. Additionally, the development of a user-friendly MATLAB App facilitates its implementation in clinical settings. Subject to external validation in clinical research settings, the HI can be more useful than existing frailty measures in the prediction of cardio-respiratory risk.

Relationship between sarcopenia and orthostatic blood pressure recovery in older falls clinic attendees.

PURPOSE: Sarcopenia and delayed orthostatic blood pressure (BP) recovery are two disorders increasingly associated with adverse clinical outcomes in older adults. There may exist a pathophysiological link between the two via the skeletal muscle pump of the lower limbs. Previously in a large population-based study, we found an association between probable sarcopenia and orthostatic BP recovery. Here, we sought to determine the association between confirmed sarcopenia and orthostatic BP recovery in falls clinic attendees aged 50 years or over. METHODS: One hundred and nine recruited patients (mean age 70 years, 58% women) underwent an active stand with non-invasive beat-to-beat haemodynamic monitoring. Hand grip strength and five-chair stands time were measured, and bioelectrical impedance analysis was performed. They were then classified as robust, probable sarcopenic or sarcopenic as per the European Working Group on Sarcopenia in Older People guidelines. Mixed effects models with linear splines were used to model the effect of sarcopenia status on orthostatic BP recovery, whilst controlling for potential confounders. RESULTS: Probable sarcopenia was identified in 32% of the sample and sarcopenia in 15%. Both probable and confirmed sarcopenia were independently associated with an attenuated rate of recovery of both systolic and diastolic BP in the 10-20 s period after standing. Attenuation was larger for confirmed than probable sarcopenia (systolic BP ß - 0.85 and - 0.59, respectively, P < 0.01; diastolic BP ß - 0.65, - 0.45, P < 0.001). CONCLUSION: Sarcopenia was independently associated with slower BP recovery during the early post-stand period. The potentially modifiable effect of the skeletal muscle pump in orthostatic haemodynamics requires further study.

Differential Associations Between Two Markers of Probable Sarcopenia and Continuous Orthostatic Hemodynamics in The Irish Longitudinal Study on Ageing.

BACKGROUND: Sarcopenia and orthostatic hypotension are growing age-related health burdens associated with adverse outcomes, including falls. Despite a possible pathophysiological link, the association between the 2 disorders is not well elucidated. We sought to investigate this relationship in The Irish Longitudinal Study on Ageing (TILDA). METHODS: Data from 2 858 participants at wave 3 of TILDA were analyzed. Probable sarcopenia was defined as per the European Working Group on Sarcopenia in Older People revised definition cutoffs (hand grip strength [HGS] <27 kg in men, <16 kg in women, and/or 5-chair stand test [5CST] time >15 seconds). Participants underwent an active stand orthostatic test with continuous blood pressure (BP) monitoring. Multilevel mixed-effects models, controlling for possible confounders, were used to assess the effect of probable sarcopenia by HGS and 5CST criteria on the change in BP after standing. RESULTS: HGS- and 5CST-defined probable sarcopenia were independently associated with an attenuated BP recovery at 10-20 seconds poststand (systolic BP: ß -0.54, p < .001; ß -0.25, p < .001). On average, those meeting HGS probable sarcopenia criteria had a significantly lower BP at 20, 30, and 40 seconds (differences in systolic BP: -5.01 mmHg, -3.68 mmHg, -2.32 mmHg, p < .05 for all). Those meeting 5CST probable sarcopenia criteria had a significant difference in systolic BP at 20 seconds (-1.94 mmHg, p = .002) but not at 30 or 40 seconds. CONCLUSION: Probable sarcopenia had a significant association with delayed orthostatic BP recovery, with HGS-defined probable sarcopenia having a stronger association than 5CST-defined probable sarcopenia. Results support a modest but significant pathophysiological link between probable sarcopenia and orthostatic hypotension.

Plasma lutein and zeaxanthin concentrations associated with musculoskeletal health and incident frailty in The Irish Longitudinal Study on Ageing (TILDA).

INTRODUCTION: Lutein and zeaxanthin are diet-derived carotenoids that are proposed to help mitigate frailty risk and age-related declines in musculoskeletal health via their anti-oxidant and anti-inflammatory properties. Therefore, this study aimed to investigate the association between lutein and zeaxanthin status and indices of musculoskeletal health and incident frailty among community-dwelling adults aged ≥50 years in the Irish Longitudinal Study on Ageing (TILDA). METHODS: Cross-sectional analyses (n = 4513) of plasma lutein and zeaxanthin concentrations and grip strength, usual gait speed, timed up-and-go (TUG), probable sarcopenia (defined as grip strength <27 kg in men, <16 kg in women), and bone mass (assessed using calcaneal broadband ultrasound stiffness index) were performed at Wave 1 (2009-2011; baseline). In the longitudinal analyses (n = 1425-3100), changes in usual gait speed (at Wave 3, 2014-2015), grip strength (Wave 4, 2016) and TUG (at Wave 5, 2018), incident probable sarcopenia (at Wave 4) and incident frailty (Fried's phenotype, Frailty Index, FRAIL Scale, Clinical Frailty Scale-classification tree, at Wave 5) were determined. Data were analysed using linear and ordinal logistic regression, adjusted for confounders. RESULTS: Cross-sectionally, plasma lutein and zeaxanthin concentrations were positively associated with usual gait speed (B [95 % CI] per 100-nmol/L higher concentration: Lutein 0.59 [0.18, 1.00], Zeaxanthin 1.46 [0.37, 2.55] cm/s) and inversely associated with TUG time (Lutein -0.07 [-0.11, -0.03], Zeaxanthin -0.14 [-0.25, -0.04] s; all p < 0.01), but not with grip strength or probable sarcopenia (p > 0.05). Plasma lutein concentration was positively associated with bone stiffness index (0.54 [0.15, 0.93], p < 0.01). Longitudinally, among participants who were non-frail at Wave 1, higher plasma lutein and zeaxanthin concentrations were associated lower odds of progressing to a higher frailty category (e.g. prefrailty or frailty) by Wave 5 (ORs 0.57-0.89, p < 0.05) based on the Fried's phenotype, FRAIL Scale and the Clinical Frailty Scale, and in the case of zeaxanthin, Frailty Index. Neither plasma lutein nor zeaxanthin concentrations were associated with changes in musculoskeletal indices or incident probable sarcopenia (p > 0.05). CONCLUSION: Higher plasma lutein and zeaxanthin concentrations at baseline were associated with a reduced likelihood of incident frailty after ~8 years of follow up. Baseline plasma lutein and zeaxanthin concentrations were also positively associated with several indices of musculoskeletal health cross-sectionally but were not predictive of longitudinal changes in these outcomes over 4-8 years.

Haemodynamic Parameters Underlying the Relationship between Sarcopenia and Blood Pressure Recovery on Standing.

BACKGROUND: Sarcopenia, delayed blood pressure (BP) recovery following standing, and orthostatic hypotension (OH) pose significant clinical challenges associated with ageing. While prior studies have established a link between sarcopenia and impaired BP recovery and OH, the underlying haemodynamic mechanisms remain unclear. METHODS: We enrolled 107 participants aged 50 and above from a falls and syncope clinic, conducting an active stand test with continuous non-invasive haemodynamic measurements. Hand grip strength and five-chair stand time were evaluated, and muscle mass was estimated using bioelectrical impedance analysis. Participants were categorised as non-sarcopenic or sarcopenic. Employing mixed-effects linear regression, we modelled the effect of sarcopenia on mean arterial pressure and heart rate after standing, as well as Modelflow®-derived parameters such as cardiac output, total peripheral resistance, and stroke volume, while adjusting for potential confounders. RESULTS: Sarcopenia was associated with diminished recovery of mean arterial pressure during the 10-20 s period post-standing (ß -0.67, p < 0.001). It also resulted in a reduced ascent to peak (0-10 s) and recovery from peak (10-20 s) of cardiac output (ß -0.05, p < 0.001; ß 0.06, p < 0.001). Furthermore, sarcopenia was associated with attenuated recovery (10-20 s) of total peripheral resistance from nadir (ß -0.02, p < 0.001) and diminished recovery from peak (10-20 s) of stroke volume (ß 0.54, p < 0.001). Notably, heart rate did not exhibit a significant association with sarcopenia status at any time interval post-standing. CONCLUSION: The compromised BP recovery observed in sarcopenia appears to be driven by an initial reduction in the peak of cardiac output, followed by attenuated recovery of cardiac output from its peak and total peripheral resistance from its nadir. This cardiac output finding seems to be influenced by stroke volume rather than heart rate. Possible mechanisms for these findings include cardio-sarcopenia, the impact of sarcopenia on the autonomic nervous system, and/or the skeletal muscle pump.

Potentially inappropriate medication use and mortality in patients with cognitive impairment.

PURPOSE: Potentially inappropriate medications (PIMs) are associated with falls, hospitalization, and cognitive decline. Few studies have investigated the association between PIMs related to cognitive impairment (PIMCog) and mortality in dementia or mild cognitive impairment (MCI). METHODS: This was a retrospective observational study. Patients diagnosed with MCI or dementia (DSM-IV criteria) presenting to a tertiary-referral memory clinic from 2013 to 2019 were eligible. The primary outcome was all-cause death. Secondary outcomes were vascular death and non-vascular death. The primary exposure variable of interest was PIMCog, defined as any medication in the Beers 2015 or STOPP criteria, classified as potentially inappropriate for patients with cognitive impairment. Anticholinergic burden was measured using the anticholinergic cognitive burden (ACB) scale. Polypharmacy was defined as ≥ 5 medications. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: Four hundred eighteen patients were included (n = 261 dementia, n = 157 MCI). The median age was 79 (interquartile range [IQR] 74-82) and median follow-up was 809 days (IQR 552-1571). One or more PIMCog was prescribed in 141 patients (33.4%). PIMCog use was associated with all-cause mortality after adjustment for age, sex, dementia severity, Charlson's Co-morbidity Index, chronic obstructive pulmonary disease, congestive cardiac failure, and peripheral vascular disease (HR 1.96, 95% CI 1.24-3.09). PIMCog use was associated with vascular death (HR 3.28, 95% CI 1.51-7.11) but not with non-vascular death (HR 1.40 95% CI 0.78-2.52). CONCLUSION: PIMCog use in patients with cognitive impairment is high. It is independently associated with all-cause mortality and vascular death. This is a potential modifiable risk factor for death in this patient cohort. Further research is required to independently validate this finding.

Enhancing referral processes within an integrated fall prevention pathway for older people: a mixed-methods study.

OBJECTIVES: Multifactorial interventions, which involve assessing an individual's risk of falling and providing treatment or onward referral, require coordination across settings. Using a mixed-methods design, we aimed to develop a process map to examine onward referral pathways following falls risk assessment in primary care. SETTING: Primary care fall risk assessment clinics in the South of Ireland. PARTICIPANTS: Focus groups using participatory mapping techniques with primary care staff (public health nurses (PHNs), physiotherapists (PT),and occupational therapists (OT)) were conducted to plot the processes and onward referral pathways at each clinic (n=5). METHODS: Focus groups were analysed in NVivo V.12 using inductive thematic analysis. Routine administrative data from January to March 2018 included details of client referrals, assessments and demographics sourced from referral and assessment forms. Data were analysed in Stata V.12 to estimate the number, origin and focus of onward referrals and whether older adults received follow-up interventions. Quantitative and qualitative data were analysed separately and integrated to produce a map of the service. RESULTS: Nine staff participated in three focus groups and one interview (PHN n=2; OT n=4; PT n=3). 85 assessments were completed at five clinics (female n=69, 81.2%, average age 77). The average number of risk factors was 5.4 out of a maximum of 10. Following assessment, clients received an average of three onward referrals. Only one-third of referrals (n=135/201, 33%) had data available on intervention receipt. Primary care staff identified variations in how formally onward referrals were managed and barriers, including a lack of client information, inappropriate referral and a lack of data management support. CONCLUSION: Challenges to onward referral manifest early in an integrated care pathway, such as clients with multiple risk factors sent for initial assessment and the lack of an integrated IT system to share information across settings.

Longitudinal Study on Sustained Attention to Response Task (SART): Clustering Approach for Mobility and Cognitive Decline.

The Sustained Attention to Response Task (SART) is a computer-based go/no-go task to measure neurocognitive function in older adults. However, simplified average features of this complex dataset lead to loss of primary information and fail to express associations between test performance and clinically meaningful outcomes. Here, we combine a novel method to visualise individual trial (raw) information obtained from the SART test in a large population-based study of ageing in Ireland and an automatic clustering technique. We employed a thresholding method, based on the individual trial number of mistakes, to identify poorer SART performances and a fuzzy clusters algorithm to partition the dataset into 3 subgroups, based on the evolution of SART performance after 4 years. Raw SART data were available for 3468 participants aged 50 years and over at baseline. The previously reported SART visualisation-derived feature 'bad performance', indicating the number of SART trials with at least 4 mistakes, and its evolution over time, combined with the fuzzy c-mean (FCM) algorithm, individuated 3 clusters corresponding to 3 degrees of physiological dysregulation. The biggest cluster (94% of the cohort) was constituted by healthy participants, a smaller cluster (5% of the cohort) by participants who showed improvement in cognitive and psychological status, and the smallest cluster (1% of the cohort) by participants whose mobility and cognitive functions dramatically declined after 4 years. We were able to identify in a cohort of relatively high-functioning community-dwelling adults a very small group of participants who showed clinically significant decline. The selected smallest subset manifested not only mobility deterioration, but also cognitive decline, the latter being usually hard to detect in population-based studies. The employed techniques could identify at-risk participants with more specificity than current methods, and help clinicians better identify and manage the small proportion of community-dwelling older adults who are at significant risk of functional decline and loss of independence.

Comprehensive Clinical Characterisation of Brain Fog in Adults Reporting Long COVID Symptoms.

(1) Introduction: A subset of individuals experiencing long COVID symptoms are affected by 'brain fog', a lay term that often refers to general cognitive dysfunction but one that is still poorly characterised. In this study, a comprehensive clinical characterisation of self-reported brain fog was conducted vis-à-vis other long COVID symptoms and parameters of mental, cognitive, and physical health. (2) Methodology: Adult participants reporting long COVID symptoms were recruited from hospital clinics and as self-referrals. Participants completed a battery of questionnaires and clinical assessments, including COVID-19 history, symptomatology, self-reported scales (Chalder Fatigue Scale [CFQ], Center for Epidemiological Studies Depression Scale, and Impact of Events Scale-Revised), computer-based cognitive assessments (simple response time and choice reaction time tasks), physical performance tests (gait velocity and muscle strength assessments), and an orthostatic active stand test. A systematic comparison between participants with and without self-reported brain fog was conducted, and a backwards binary logistic regression model was computed to identify the strongest independent associations with brain fog. This was complemented by an automatic cluster analysis to rank the importance of associations. Finally, a structural equation model was postulated with a causal model of key symptomatic indicators and functional consequences of brain fog as a latent variable. (3) Results: Of 108 participants assessed, brain fog was a self-reported symptom in 71 (65.7%) participants. Those with brain fog were at a longer point in time since COVID-19 onset and reported longer duration of low activity during the acute illness. When assessed, those with brain fog had higher frequencies of subjective memory impairment, word-finding difficulties, dizziness, myalgia, arthralgia, hyperhidrosis, cough, voice weakness, throat pain, visual and hearing problems, dysosmia, paraesthesia, chest pain, skin rashes, and hair loss; mean scores in fatigue, depression, and post-traumatic stress scales were higher; performance in both computer-based cognitive tasks was poorer; and measured gait speed and grip strength were lower. The logistic regression suggested that the best independent associations with brain fog were memory impairment, CFQ, and myalgia. The cluster analysis suggested that the most important associations with brain fog were CFQ, dizziness, myalgia, reduced gait speed, word-finding difficulties, reduced grip strength, and memory impairment. The SEM was consistent with key indicators of brain fog being CFQ, dizziness, myalgia, word-finding difficulties, and memory impairment; and reduced grip strength, gait speed, and cognitive response times its functional consequences. (4) Conclusions: The findings indicate that self-reported brain fog in long COVID is a recognisable symptom cluster primarily characterised by fatigue, dizziness, myalgia, word-finding difficulties, and memory impairment and has adverse psychological and psychomotor correlates. In long COVID, brain fog should be regarded as a wide-ranging symptom and addressed holistically with medical, psychological, and rehabilitative supports as guided by individual needs.

Cardiovascular Signal Entropy Predicts All-Cause Mortality: Evidence from The Irish Longitudinal Study on Ageing (TILDA).

In this study, the relationship between cardiovascular signal entropy and the risk of seven-year all-cause mortality was explored in a large sample of community-dwelling older adults from The Irish Longitudinal Study on Ageing (TILDA). The hypothesis under investigation was that physiological dysregulation might be quantifiable by the level of sample entropy (SampEn) in continuously noninvasively measured resting-state systolic (sBP) and diastolic (dBP) blood pressure (BP) data, and that this SampEn measure might be independently predictive of mortality. Participants' date of death up to 2017 was identified from official death registration data and linked to their TILDA baseline survey and health assessment data (2010). BP was continuously monitored during supine rest at baseline, and SampEn values were calculated for one-minute and five-minute sections of this data. In total, 4543 participants were included (mean (SD) age: 61.9 (8.4) years; 54.1% female), of whom 214 died. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) with 95% confidence intervals (CIs) for the associations between BP SampEn and all-cause mortality. Results revealed that higher SampEn in BP signals was significantly predictive of mortality risk, with an increase of one standard deviation in sBP SampEn and dBP SampEn corresponding to HRs of 1.19 and 1.17, respectively, in models comprehensively controlled for potential confounders. The quantification of SampEn in short length BP signals could provide a novel and clinically useful predictor of mortality risk in older adults.

Predictors of Submaximal Exercise Test Attainment in Adults Reporting Long COVID Symptoms.

Adults with long COVID often report intolerance to exercise. Cardiopulmonary exercise testing (CPET) has been used in many settings to measure exercise ability but has been conducted in a few long COVID cohorts. We conducted CPET in a sample of adults reporting long COVID symptoms using a submaximal cycle ergometer protocol. We studied pre-exercise predictors of achieving 85% of the age-predicted maximum heart rate (85%HRmax) using logistic regression. Eighty participants were included (mean age 46 years, range 25−78, 71% women). Forty participants (50%) did not reach 85%HRmax. On average, non-achievers reached 84% of their predicted 85%HRmax. No adverse events occurred. Participants who did not achieve 85%HRmax were older (p < 0.001), had more recent COVID-19 illness (p = 0.012) with higher frequency of hospitalization (p = 0.025), and had been more affected by dizziness (p = 0.041) and joint pain (p = 0.028). In the logistic regression model including age, body mass index, time since COVID-19, COVID-19-related hospitalization, dizziness, joint pain, pre-existing cardiopulmonary disease, and use of beta blockers, independent predictors of achieving 85%HRmax were younger age (p = 0.001) and longer time since COVID-19 (p = 0.008). Our cross-sectional findings suggest that exercise tolerance in adults with long COVID has potential to improve over time. Longitudinal research should assess the extent to which this may occur and its mechanisms. ClinicalTrials.gov identifier: NCT05027724 (TROPIC Study).

A Novel Methodology for the Synchronous Collection and Multimodal Visualization of Continuous Neurocardiovascular and Neuromuscular Physiological Data in Adults with Long COVID.

Background: Reports suggest that adults with post-COVID-19 syndrome or long COVID may be affected by orthostatic intolerance syndromes, with autonomic nervous system dysfunction as a possible causal factor of neurocardiovascular instability (NCVI). Long COVID can also manifest as prolonged fatigue, which may be linked to neuromuscular function impairment (NMFI). The current clinical assessment for NCVI monitors neurocardiovascular performance upon the application of orthostatic stressors such as an active (i.e., self-induced) stand or a passive (tilt table) standing test. Lower limb muscle contractions may be important in orthostatic recovery via the skeletal muscle pump. In this study, adults with long COVID were assessed with a protocol that, in addition to the standard NCVI tests, incorporated simultaneous lower limb muscle monitoring for NMFI assessment. Methods: To conduct such an investigation, a wide range of continuous non-invasive biomedical sensing technologies were employed, including digital artery photoplethysmography for the extraction of cardiovascular signals, near-infrared spectroscopy for the extraction of regional tissue oxygenation in brain and muscle, and electromyography for assessment of timed muscle contractions in the lower limbs. Results: With the proposed methodology described and exemplified in this paper, we were able to collect relevant physiological data for the assessment of neurocardiovascular and neuromuscular functioning. We were also able to integrate signals from a variety of instruments in a synchronized fashion and visualize the interactions between different physiological signals during the combined NCVI/NMFI assessment. Multiple counts of evidence were collected, which can capture the dynamics between skeletal muscle contractions and neurocardiovascular responses. Conclusions: The proposed methodology can offer an overview of the functioning of the neurocardiovascular and neuromuscular systems in a combined NCVI/NMFI setup and is capable of conducting comparative studies with signals from multiple participants at any given time in the assessment. This could help clinicians and researchers generate and test hypotheses based on the multimodal inspection of raw data in long COVID and other cohorts.

Orthostatic Intolerance in Adults Reporting Long COVID Symptoms Was Not Associated With Postural Orthostatic Tachycardia Syndrome.

In this observational cross-sectional study, we investigated predictors of orthostatic intolerance (OI) in adults reporting long COVID symptoms. Participants underwent a 3-min active stand (AS) with Finapres® NOVA, followed by a 10-min unmedicated 70° head-up tilt test. Eighty-five participants were included (mean age 46 years, range 25-78; 74% women), of which 56 (66%) reported OI during AS (OIAS). OIAS seemed associated with female sex, more fatigue and depressive symptoms, and greater inability to perform activities of daily living (ADL), as well as a higher heart rate (HR) at the lowest systolic blood pressure (SBP) point before the first minute post-stand (mean HRnadir: 88 vs. 75 bpm, P = 0.004). In a regression model also including age, sex, fatigue, depression, ADL inability, and peak HR after the nadir SBP, HRnadir was the only OIAS predictor (OR = 1.09, 95% CI: 1.01-1.18, P = 0.027). Twenty-two (26%) participants had initial (iOH) and 5 (6%) classical (cOHAS) orthostatic hypotension, but neither correlated with OIAS. Seventy-one participants proceeded to tilt, of which 28 (39%) had OI during tilt (OItilt). Of the 53 who had a 10-min tilt, 7 (13%) had an HR increase >30 bpm without cOHtilt (2 to HR > 120 bpm), but six did not report OItilt. In conclusion, OIAS was associated with a higher initial HR on AS, which after 1 min equalised with the non-OIAS group. Despite these initial orthostatic HR differences, POTS was infrequent (2%). ClinicalTrials.gov Identifier: NCT05027724 (retrospectively registered on August 30, 2021).

Blood Pressure Signal Entropy as a Novel Marker of Physical Frailty: Results from the FRAILMatics Clinical Cohort.

In this study we investigated the association between information entropy in short length blood pressure signals and physical frailty status, in a group of patients aged 50+ recruited from the Falls and Syncope Unit at the Mercer's Institute for Successful Ageing in St James's Hospital, Dublin, Ireland. This work is an external clinical validation of findings previously derived in a population-based cohort from The Irish Longitudinal Study on Ageing (TILDA). The hypothesis under investigation was that dysregulation (as quantified by entropy) in continuous non-invasive blood pressure signals could provide a clinically useful marker of physical frailty status. We found that in the 100 patients investigated, higher entropy in continuously measured resting state diastolic blood pressure was associated with worse physical frailty score, as measured by the Frailty Instrument for primary care of the Survey of Health, Ageing and Retirement in Europe (SHARE-FI). Since physical frailty is defined as a pre-disability state and hence it can be difficult for clinicians to identify at an early stage, the quantification of entropy in short length cardiovascular signals could provide a clinically useful marker of the physiological dysregulations that underlie physical frailty, potentially aiding in identifying individuals at higher risk of adverse health outcomes.

SART and Individual Trial Mistake Thresholds: Predictive Model for Mobility Decline.

The Sustained Attention to Response Task (SART) has been used to measure neurocognitive functions in older adults. However, simplified average features of this complex dataset may result in loss of primary information and fail to express associations between test performance and clinically meaningful outcomes. Here, we describe a new method to visualise individual trial (raw) information obtained from the SART test, vis-à-vis age, and groups based on mobility status in a large population-based study of ageing in Ireland. A thresholding method, based on the individual trial number of mistakes, was employed to better visualise poorer SART performances, and was statistically validated with binary logistic regression models to predict mobility and cognitive decline after 4 years. Raw SART data were available for 4864 participants aged 50 years and over at baseline. The novel visualisation-derived feature bad performance, indicating the number of SART trials with at least 4 mistakes, was the most significant predictor of mobility decline expressed by the transition from Timed Up-and-Go (TUG) < 12 to TUG ≥ 12 s (OR = 1.29; 95% CI 1.14-1.46; p < 0.001), and the only significant predictor of new falls (OR = 1.11; 95% CI 1.03-1.21; p = 0.011), in models adjusted for multiple covariates. However, no SART-related variables resulted significant for the risk of cognitive decline, expressed by a decrease of ≥2 points in the Mini-Mental State Examination (MMSE) score. This novel multimodal visualisation could help clinicians easily develop clinical hypotheses. A threshold approach to the evaluation of SART performance in older adults may better identify subjects at higher risk of future mobility decline.

Admissions for orthostatic hypotension: an analysis of NHS England Hospital Episode Statistics data.

OBJECTIVES: To determine whether admissions for orthostatic hypotension (OH) and its consequences, such as falls, have changed over the past 10 years in the National Health Service (NHS) England. SETTING: Data from NHS England Hospital Episode Statistics, a database containing details of all admissions, accident and emergency attendances and outpatient appointments at NHS hospitals in England, were obtained and analysed. PARTICIPANTS: Data on hospital admissions in NHS England, as defined by finished consultant episodes (FCEs), were examined between 2008 and 2017. MAIN OUTCOME MEASURES: FCEs for the following International Classification of Disease codes were examined: OH (I95.1), tendency to fall (R29.6), epilepsy (G40) and chronic obstructive pulmonary disease (COPD) (J44). The total number of FCEs was also examined. RESULTS: Between 2008 and 2017, FCEs for OH rose from 14 658 to 30 759, a 110% increase. The greatest increase was in the over 75 years age group where FCEs went from 10 639 to 22 756, a 114% rise. The number of falls related FCEs in this age group rose from 61 841 to 89 622 (45%). Admissions for epilepsy and COPD rose by 7% and 35%, respectively. CONCLUSIONS: The number of admissions for OH has risen dramatically over the past 10 years, as have admissions for falls and related disorders. This rise is out of proportion with admissions for other conditions such as epilepsy and COPD. We postulate that this relates to tighter blood pressure (BP) targets. This suggests caution in the application of recent BP targets to older, frailer adults.

Time to Refocus Assessment of Vision in Older Adults? Contrast Sensitivity but Not Visual Acuity Is Associated With Gait in Older Adults.

BACKGROUND: The relationship between measures of visual function and gait related risk factors for falls is unclear. In this study, we examine the relationship between visual function (visual acuity [VA] and contrast sensitivity [CS] at multiple spatial frequencies) and quantitative spatiotemporal gait, using a large, nationally representative sample of community dwelling older adults. METHODS: Participants aged 50 and over were recruited as part of The Irish Longitudinal Study on Ageing (TILDA). VA was measured with the LogMAR chart according to the Early Treatment of Diabetic Retinopathy Study protocol. CS was measured at five spatial frequencies ranging 1.5 to 18 cycles per degree (cpd) using the Functional Acuity Contrast Test. Gait speed, cadence, and stride length were measured using the GAITRite system. Multivariate analysis examined associations between gait and visual performance parameters adjusting for socioeconomic, physical, cognitive, and mental health covariates. RESULTS: Data from 4,678 participants were analyzed (age 61.7 ± 8.3 years, 54.1% woman). Poorer CS at 1.5 cpd and 3.0 cpd (low spatial frequency) was independently associated with decreased stride length (CS at 1.5 cpd: ß = .031; p = .001 and CS at 3.0 cpd: ß = .020; p = .001) but not cadence or gait speed. There was no evidence of an association between VA and any of the gait variables considered (p > .05). CONCLUSION: Reduced CS, at low spatial frequencies, is independently associated with shorter stride length, while VA is not associated with any gait measures. This evidence suggests that it may be necessary to consider refocus of the assessment of vision to include the most appropriate measures.