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.

Slower speed of blood pressure recovery after standing is associated with accelerated brain aging: Evidence from The Irish Longitudinal Study on Ageing (TILDA).

Background: Impaired recovery of blood pressure (BP) in response to standing up is a prevalent condition in older individuals. We evaluated the relationship between the early recovery of hemodynamic responses to standing and brain health in adults over 50. Methods: Participants from The Irish Longitudinal Study on Ageing (TILDA) (n=411; age 67.6 ± 7.3 years; 53.4 % women) performed an active stand challenge while blood pressure and heart rate were continuously monitored. The recovery of these parameters was determined as the slope of the BP and HR response, following the initial drop/rise after standing. We have previously reported a novel and validated measure of brain ageing using MRI data, which measures the difference between biological brain age and chronological age, providing a brain-predicted age difference (brainPAD) score. Results: Slower recovery of systolic and diastolic BP was found to be significantly associated with higher brainPAD scores (i.e., biologically older brains), where a one-year increase in brainPAD was associated with a decrease of 0.02 mmHg/s and 0.01 mmHg/s in systolic and diastolic BP recovery, respectively, after standing. Heart rate (HR) recovery was not significantly associated with brainPAD score. Conclusion: These results demonstrate that slower systolic and diastolic BP recovery in the early phase after standing is associated with accelerated brain aging in older individuals. This suggests that the BP response to standing, measured using beat-to-beat monitoring, has the potential to be used as a marker of accelerated brain aging, relying on a simple procedure and devices that are easily accessible.

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.

Brain connectivity in frailty: Insights from The Irish Longitudinal Study on Ageing (TILDA).

Frailty in older adults is associated with greater risk of cognitive decline. Brain connectivity insights could help understand the association, but studies are lacking. We applied connectome-based predictive modeling to a 32-item self-reported Frailty Index (FI) using resting state functional MRI data from The Irish Longitudinal Study on Ageing. A total of 347 participants were included (48.9% male, mean age 68.2 years). From connectome-based predictive modeling, we obtained 204 edges that positively correlated with the FI and composed the "frailty network" characterised by connectivity of the visual network (right); and 188 edges that negatively correlated with the FI and formed the "robustness network" characterized by connectivity in the basal ganglia. Both networks' highest degree node was the caudate but with different patterns: from caudate to visual network in the frailty network; and to default mode network in the robustness network. The FI was correlated with walking speed but not with metrics of global cognition, reinforcing the matching between the FI and the brain connectivity pattern found (main predicted connectivity in basal ganglia).

Connectome-based predictive modelling of cognitive reserve using task-based functional connectivity.

Cognitive reserve supports cognitive function in the presence of pathology or atrophy. Functional neuroimaging may enable direct and accurate measurement of cognitive reserve which could have considerable clinical potential. The present study aimed to develop and validate a measure of cognitive reserve using task-based fMRI data that could then be applied to independent resting-state data. Connectome-based predictive modelling with leave-one-out cross-validation was applied to predict a residual measure of cognitive reserve using task-based functional connectivity from the Cognitive Reserve/Reference Ability Neural Network studies (n = 220, mean age = 51.91 years, SD = 17.04 years). This model generated summary measures of connectivity strength that accurately predicted a residual measure of cognitive reserve in unseen participants. The theoretical validity of these measures was established via a positive correlation with a socio-behavioural proxy of cognitive reserve (verbal intelligence) and a positive correlation with global cognition, independent of brain structure. This fitted model was then applied to external test data: resting-state functional connectivity data from The Irish Longitudinal Study on Ageing (TILDA, n = 294, mean age = 68.3 years, SD = 7.18 years). The network-strength predicted measures were not positively associated with a residual measure of cognitive reserve nor with measures of verbal intelligence and global cognition. The present study demonstrated that task-based functional connectivity data can be used to generate theoretically valid measures of cognitive reserve. Further work is needed to establish if, and how, measures of cognitive reserve derived from task-based functional connectivity can be applied to independent resting-state data.

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.

Tooth loss and regional grey matter volume.

OBJECTIVES: To investigate whether tooth loss was associated with regional grey matter volume (GMV) in a group of community dwelling older men and women from Ireland. METHODS: A group of 380 dementia-free men and women underwent a dental examination and had a Magnetic Resonance Imaging (MRI) scan as part of The Irish Longitudinal Study of Aging (TILDA). Cortical parcellation was conducted using Freesurfer utilities to produce volumetric measures of gyral based regions of interest. Analysis included multiple linear regression to investigate the association between tooth loss and regional GMVs with adjustment for various confounders. RESULTS: The mean age of participants was 68.1 years (SD 7.3) and 51.6% of the group were female. 50 (13.2%) of the participants were edentulous, 148 (38.9%) had 1-19 teeth, and 182 (47.9%) had ≥20 teeth. Multiple liner regression analysis with adjustment for a range of potential confounders showed associations between the number of teeth and GMVs in the paracentral lobule and the cuneus cortex. In the paracentral lobule, comparing participants with 1-19 teeth versus edentates there was an increase in GMV of ß=323.0mm3 (95% Confidence Interval [CI] 84.5, 561.6) and when comparing participants with ≥20 teeth to edentates there was an increase of ß=382.3mm3 (95% CI 126.9, 637.7). In the cuneus cortex, comparing participants with ≥20 teeth to edentates there was an increase in GMV of ß=380.5mm3 (95% CI 69.4, 691.5). CONCLUSIONS: In this group of older men and women from Ireland, the number of teeth was associated with GMVs in the paracentral lobule and the cuneus cortex independent of various known confounders. CLINICAL SIGNIFICANCE: Although not proof of causation, the finding that tooth loss was associated with regional reduced GMV in the brain may represent a potential explanatory link to the observed association between tooth loss and cognitive decline.

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.

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.

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.

Tooth loss and cognitive decline in community dwelling older Irish adults: A cross-sectional cohort study.

OBJECTIVES: To investigate whether tooth loss and related loss of occluding tooth pairs, were associated with cognitive decline in a group of community dwelling older men and women from Ireland. METHODS: A group of 2508 men and women, aged 50-93 years, underwent a dental examination as part of The Irish Longitudinal Study of ageing (TILDA). Global cognitive function was assessed using the mini-mental state examination (MMSE). Analysis included multiple logistic regression with adjustment for various confounders. RESULTS: The mean age of participants was 65.5 years (SD 8.1) and 55.3% of the group were female. Three hundred and twenty-nine (13.1%) of the cohort were classified as having a low MMSE with a score ≤ 27. After adjustment for confounding variables, compared to subjects with ≥ 20 teeth, the odds ratio for a low MMSE amongst edentulous was 1.55 (95% CI 1.03-2.34) p = 0.03, and for those with 1-19 teeth was 1.38 (95% CI 1.03-1.84) p = 0.04. Having < 10 natural occluding pairs and < 4 posterior occluding pairs also associated with a low MMSE. CONCLUSIONS: In this cross-sectional cohort study, tooth loss and related loss of occluding tooth pairs were associated with a low MMSE in a group of older adults from Ireland, independent of various known confounders. CLINICAL SIGNIFICANCE: Dentists should be aware of the potential systemic health implications of patients presenting with tooth loss. Tooth loss may be an important risk indicator for cognitive decline.

Impaired Stabilization of Orthostatic Cerebral Oxygenation Is Associated With Slower Gait Speed: Evidence From The Irish Longitudinal Study on Ageing.

BACKGROUND: Cerebral autoregulation (CAR) systems maintain blood flow to the brain across a wide range of blood pressures. Deficits in CAR have been linked to gait speed (GS) but previous studies had small sample sizes and used specialized equipment which impede clinical translation. The purpose of this work was to assess the association between GS and orthostatic cerebral oxygenation in a large, community-dwelling sample of older adults. METHOD: Data for this study came from the Irish Longitudinal Study on Ageing. A near-infrared spectroscopy (NIRS) device attached to the forehead of each participant (n = 2 708) was used to track tissue saturation index (TSI; the ratio of oxygenated to total hemoglobin) during standing. GS was assessed using a portable walkway. RESULTS: Recovery was impaired in slower GS participants with a TSI value at 20 seconds (after standing) of -0.55% (95% CI: -0.67, -0.42) below baseline in the slowest GS quartile versus -0.14% (95% CI: -0.25, -0.04) in the fastest quartile. Slower GS predicted a lower TSI throughout the 3-minute monitoring period. Results were not substantially altered by adjusting for orthostatic hypotension. Adjustment for clinical and demographic covariates attenuated the association between but differences remained between GS quartiles from 20 seconds to 3 minutes after standing. CONCLUSION: This study reported evidence for impaired recovery of orthostatic cerebral oxygenation depending on GS in community-dwelling older adults. Future work assessing NIRS as a clinical tool for monitoring the relationship between GS and cerebral regulation is warranted.

Sleep duration, sleep problems, and perceived stress are associated with hippocampal subfield volumes in later life: findings from The Irish Longitudinal Study on Ageing.

STUDY OBJECTIVES: This study examines the cross-sectional and 2-year follow-up relationships between sleep and stress and total hippocampal volume and hippocampal subfield volumes among older adults. METHODS: Four hundred seventeen adults (aged 68.8 ± 7.3; 54% women) from the Irish Longitudinal Study on Ageing completed an interview, a questionnaire, and multiparametric brain magnetic resonance imaging. The relationships between self-reported sleep duration, sleep problems, perceived stress, and total hippocampal volume were examined by using ordinary least squares regressions. Linear mixed-effects models were used to investigate the relationships between sleep duration, sleep problems, perceived stress, changes in these measures over 2-years, and hippocampal subfield volumes. RESULTS: No cross-sectional and follow-up associations between sleep and total hippocampal volume and between stress and total hippocampal volume were found. By contrast, Long sleep (≥9-10 h/night) was associated with smaller volumes of molecular layer, hippocampal tail, presubiculum, and subiculum. The co-occurrence of Short sleep (≤6 h) and perceived stress was associated with smaller cornu ammonis 1, molecular layer, subiculum, and tail. Sleep problems independently and in conjunction with higher stress, and increase in sleep problems over 2 years were associated with smaller volumes of these same subfields. CONCLUSION: Our study highlights the importance of concurrently assessing suboptimal sleep and stress for phenotyping individuals at risk of hippocampal subfield atrophy.

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.

Associations between Cardiovascular Signal Entropy and Cognitive Performance over Eight Years.

In this study, the relationship between non-invasively measured cardiovascular signal entropy and global cognitive performance was explored in a sample of community-dwelling older adults from The Irish Longitudinal Study on Ageing (TILDA), both cross-sectionally at baseline (n = 4525; mean (SD) age: 61.9 (8.4) years; 54.1% female) and longitudinally. We hypothesised that signal disorder in the cardiovascular system, as quantified by short-length signal entropy during rest, could provide a marker for cognitive function. Global cognitive function was assessed via Mini Mental State Examination (MMSE) across five longitudinal waves (8 year period; n = 4316; mean (SD) age: 61.9 (8.4) years; 54.4% female) and the Montreal Cognitive Assessment (MOCA) across two longitudinal waves (4 year period; n = 3600; mean (SD) age: 61.7 (8.2) years; 54.1% female). Blood pressure (BP) was continuously monitored during supine rest at baseline, and sample entropy values were calculated for one-minute and five-minute sections of this data, both for time-series data interpolated at 5 Hz and beat-to-beat data. Results revealed significant associations between BP signal entropy and cognitive performance, both cross-sectionally and longitudinally. Results also suggested that as regards associations with cognitive performance, the entropy analysis approach used herein potentially outperformed more traditional cardiovascular measures such as resting heart rate and heart rate variability. The quantification of entropy in short-length BP signals could provide a clinically useful marker of the cardiovascular dysregulations that potentially underlie cognitive decline.

The Importance of Age in the Prediction of Mortality by a Frailty Index: A Machine Learning Approach in the Irish Longitudinal Study on Ageing.

The quantification of biological age in humans is an important scientific endeavor in the face of ageing populations. The frailty index (FI) methodology is based on the accumulation of health deficits and captures variations in health status within individuals of the same age. The aims of this study were to assess whether the addition of age to an FI improves its mortality prediction and whether the associations of the individual FI items differ in strength. We utilized data from The Irish Longitudinal Study on Ageing to conduct, by sex, machine learning analyses of the ability of a 32-item FI to predict 8-year mortality in 8174 wave 1 participants aged 50 or more years. By wave 5, 559 men and 492 women had died. In the absence of age, the FI was an acceptable predictor of mortality with AUCs of 0.7. When age was included, AUCs improved to 0.8 in men and 0.9 in women. After age, deficits related to physical function and self-rated health tended to have higher importance scores. Not all FI variables seemed equally relevant to predict mortality, and age was by far the most relevant feature. Chronological age should remain an important consideration when interpreting the prognostic significance of an FI.

Frailty index transitions over eight years were frequent in The Irish Longitudinal Study on Ageing.

Background: The frailty index (FI) is based on accumulation of health deficits. FI cut-offs define non-frail, prefrail and frail states. We described transitions of FI states in The Irish Longitudinal Study on Ageing (TILDA). Methods: Participants aged ≥50 years with information for a 31-deficit FI at wave 1 (2010) were followed-up over four waves (2012, 2014, 2016, 2018). Transitions were visualized with alluvial plots and probabilities estimated with multi-state Markov models, investigating the effects of age, sex and education. Results: 8174 wave 1 participants were included (3744 men and 4430 women; mean age 63.8 years). Probabilities from non-frail to prefrail, and non-frail to frail were 18% and 2%, respectively. Prefrail had a 19% probability of reversal to non-frail, and a 15% risk of progression to frail. Frail had a 21% probability of reversal to prefrail and 14% risk of death. Being older and female increased the risk of adverse FI state transitions, but being female reduced the risk of transition from frail to death. Higher level of education was associated with improvement from prefrail to non-frail. Conclusions: FI states are characterized by dynamic longitudinal transitions and frequent improvement. Opportunities exist for reducing the probability of adverse transitions.

Eight Orthostatic Haemodynamic Patterns in The Irish Longitudinal Study on Ageing (TILDA): Stability and Clinical Associations after 4 Years.

Previous research cross-sectionally characterised eight morphological systolic blood pressure (SBP) active stand (AS) patterns using a clinical clustering approach at Wave 1 (W1) of the Irish Longitudinal Study on Ageing. We explored the longitudinal stability and clinical associations of these groupings at Wave 3 (W3), four years later. Eight AS groups had their clinical characteristics and AS patterns at W3 compared to W1. We explored longitudinal associations (new cognitive decline, falls, syncope, disability, and mortality) using multivariate logistic regression models. In total, 2938 participants (60% of Wave 1 sample) had adequate AS data from both W1 and 3 for analysis. We found no longitudinal stability of the eight AS groups or their morphological patterns between the waves. A pattern of impaired stabilisation and late deficit seemed more preserved and was seen in association with new cognitive decline (OR 1.63, 95% CI: 1.12-2.36, p = 0.011). An increase in antihypertensive usage seemed associated with reduced immediate SBP drops, improved AS patterns, and reduced orthostatic intolerance (OI). In pure longitudinal groups, AS patterns were not preserved after 4 years. AS patterns are longitudinally dynamic, and improvements after 4 years are possible even in the presence of higher antihypertensive burden.