White matter fibre density in the brain's inhibitory control network is associated with falling in low activity older adults.

Recent research has indicated that the relationship between age-related cognitive decline and falling may be mediated by the individual's capacity to quickly cancel or inhibit a motor response. This longitudinal investigation demonstrates that higher white matter fibre density in the motor inhibition network paired with low physical activity was associated with falling in elderly participants. We measured the density of white matter fibre tracts connecting key nodes in the inhibitory control network in a large sample (n = 414) of older adults. We modelled their self-reported frequency of falling over a 4-year period with white matter fibre density in pathways corresponding to the direct and hyperdirect cortical-subcortical loops implicated in the inhibitory control network. Only connectivity between right inferior frontal gyrus and right subthalamic nucleus was associated with falling as measured cross-sectionally. The connectivity was not, however, predictive of future falling when measured 2 and 4 years later. Higher white matter fibre density was associated with falling, but only in combination with low levels of physical activity. No such relationship existed for selected control brain regions that are not implicated in the inhibitory control network. Albeit statistically robust, the direction of this effect was counterintuitive (more dense connectivity associated with falling) and warrants further longitudinal investigation into whether white matter fibre density changes over time in a manner correlated with falling, and mediated by physical activity.

Nutrition is associated with differences in multisensory integration in healthy older adults.

Diet can influence cognitive functioning in older adults and is a modifiable risk factor for cognitive decline. However, it is unknown if an association exists between diet and lower-level processes in the brain underpinning cognition, such as multisensory integration. We investigated whether temporal multisensory integration is associated with daily intake of fruit and vegetables (FV) or products high in fat/sugar/salt (FSS) in a large sample (N = 2,693) of older adults (mean age = 64.06 years, SD = 7.60; 56% female) from The Irish Longitudinal Study on Ageing (TILDA). Older adults completed a Food Frequency Questionnaire from which the total number of daily servings of FV and FSS items respectively was calculated. Older adults' susceptibility to the Sound Induced Flash Illusion (SIFI) measured the temporal precision of audio-visual integration, which included three audio-visual Stimulus Onset Asynchronies (SOAs): 70, 150 and 230 ms. Older adults who self-reported a higher daily consumption of FV were less susceptible to the SIFI at the longest versus shortest SOAs (i.e. increased temporal precision) compared to those reporting the lowest daily consumption (p = .013). In contrast, older adults reporting a higher daily consumption of FSS items were more susceptible to the SIFI at the longer versus shortest SOAs (i.e. reduced temporal precision) compared to those reporting the lowest daily consumption (p < .001). The temporal precision of multisensory integration is differentially associated with levels of daily consumption of FV versus products high in FSS, consistent with broader evidence that habitual diet is associated with brain health.

Cardiovascular disease and the risk of incident falls and mortality among adults aged ≥ 65 years presenting to the emergency department: a cohort study from national registry data in Denmark.

BACKGROUND: Falls cause 58% of injury-related Emergency Department (ED) attendances. Previous research has highlighted the potential role of cardiovascular risk factors for falls. This study investigated the impact of cardiovascular disease (CVD) risk on three-year incident falls, with presentation to the ED, and mortality. METHODS: A matched cohort study design was employed using national registry data from 82,292 adults (33% male) aged ≥ 65 years living in Denmark who attended the ED in 2013. We compared age and gender matched ED attendees presenting with a fall versus another reason. The cohort was followed for three-year incident falls, with presentation to the ED, and mortality. The impact of falls-related CVDs was also examined. RESULTS: Three-year incident falls was twofold higher among age and gender matched ED attendees aged ≥ 65 years presenting with a fall versus another reason at baseline. A presentation of falls with hip fracture had the highest percentage of incident falls in the 65-74 age group (22%) and the highest percentage mortality in all age groups (27-62%). CVD was not a significant factor in presenting with a fall at the ED, nor did it contribute significantly to the prediction of three-year incident falls. CVD was strongly associated with mortality risk among the ED fall group (RR = 1.81, 95% CI: 1.67-1.97) and showed interactions with both age and fall history. CONCLUSION: In this large study of adults aged ≥ 65 years attending the ED utilising data from national administrative registers in Denmark, we confirm that older adults attending the ED with a fall, including those with hip fracture, were at greatest risk for future falls. While CVD did not predict incident falls, it increased the risk of mortality in the three-year follow up with advancing age. This may be informative for the provision of care pathways for older adults attending the ED due to a fall.

Frailty on the island of Ireland: evidence from the NICOLA and TILDA studies.

BACKGROUND: Aimed to compare the prevalence, characteristics, and associated mortality risk of frailty in Northern Ireland (NI) and the Republic of Ireland (ROI). METHODS: Secondary analysis of the first wave of two nationally representative cohorts, the Northern Ireland Cohort for the Longitudinal Study of Ageing or NICOLA study (N = 8504) and the Irish Longitudinal Study on Ageing or TILDA study (N = 8504). Frailty was assessed using a harmonized accumulation deficits frailty index (FI) containing 30 items. FI scores classified individuals as non-frail (<0.10), pre-frail (0.10-0.24) and frail (≥0.25). Linkage to respective administrative data sources provided mortality information with a follow-up time of 8 years. RESULTS: The prevalence of frailty was considerably higher in NI compared with the ROI (29.0% compared with 15.0%), though pre-frailty was slightly lower (35.8% and 37.3%, respectively). Age, female sex, and lower socio-economic status were consistently associated with a higher likelihood of both pre-frailty and frailty. In the pooled analysis, both frailty and pre-frailty were higher in NI (RR = 2.68, 95% CIs 2.45, 2.94 and RR = 1.30, 95% CIs 1.21, 1.40, respectively). Frailty was associated with an increased mortality risk in both cohorts, even after full adjustment for all other characteristics, being marginally higher in TILDA than in NICOLA (HR = 2.43, 95% CIs 2.03, 2.91 vs. HR = 2.31, 95% CIs 1.90, 2.79). CONCLUSIONS: Frailty is a major public health concern for both jurisdictions. Further research and monitoring are required to elucidate why there is a higher prevalence in NI and to identify factors in early life that may be driving these differences.

Examining mental health and autonomic function as putative mediators of the relationship between sleep and trajectories of cognitive function: findings from the Irish longitudinal study on ageing (TILDA).

OBJECTIVES: This study investigates the mediating roles of autonomic function and mental health in the association between sleep and cognitive decline in adults aged 50 and above. METHOD: A total of 2,697 participants with observations on sleep and mediators at baseline and repeated measures of cognitive function (MMSE) were included. Clusters of individuals with similar cognitive trajectories (high-stable, mid-stable and low-declining) were identified. Multinomial logistic regressions were used to estimate the likelihood of membership to each trajectory group based on sleep duration and disturbance. Finally, mediation analysis tested potential mediating effects of autonomic function and mental health underpinning the sleep-cognition relationship. RESULTS: Short (p = .028), long (p =.019), and disturbed sleep (p =.008) increased the likelihood of a low-declining cognitive trajectory. Mental health measures fully attenuated relationships between cognitive decline and short or disturbed sleep but not long sleep. No autonomic function mediation was observed. CONCLUSION: Older adults with short or disturbed sleep are at risk of cognitive decline due to poor mental health. Individuals with long sleep are also at risk, however, the acting pathways remain to be identified. These outcomes have clinical implications, potentially identifying intervention strategies targeting mental health and sleep as prophylactic measures against dementia.

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.

The Impact of Type 2 Diabetes on Peripheral and Cerebral Hemodynamic Responses to Active Stand.

BACKGROUND: Although type 2 diabetes mellitus (T2DM) is an established risk factor for cognitive impairment, the underlying mechanisms remain poorly explored. One potential mechanism may be through effects of T2DM on cerebral perfusion. The current study hypothesized that T2DM is associated with altered peripheral and central hemodynamic responses to orthostasis, which may in turn be associated with cognitive impairment in T2DM. METHODS: A novel use of function-on-scalar regression, which allows the entire hemodynamic response curve to be modeled, was employed to assess the association between T2DM and hemodynamic responses to orthostasis. Logistic regression was used to assess the relationship between tissue saturation index (TSI), T2DM, and cognitive impairment. All analyses used cross-sectional data from Wave 3 of The Irish Longitudinal Study on Ageing (TILDA). RESULTS: Of 2 984 older adults (aged 64.3 ±â€…8.0; 55% female), 189 (6.3%) had T2DM. T2DM was associated with many features that are indicative of autonomic dysfunction including a blunted peak heart rate and lower diastolic blood pressure. T2DM was associated with reduced TSI and also with greater odds of impaired performance on the Montreal Cognitive Assessment (odds ratio [OR]: 1.62; confidence interval [CI: 1.07, 2.56]; p = .019). Greater TSI was associated with lower odds of impaired performance (OR: 0.90, CI [0.81-0.99]; p = .047). CONCLUSIONS: T2DM was associated with impaired peripheral and cerebral hemodynamic responses to active stand. Both T2DM and reduced cerebral perfusion were associated with impaired cognitive performance. Altered cerebral perfusion may represent an important mechanism linking T2DM and adverse brain health outcomes in older adults.

The lived experience of frailty: beyond classification and towards a holistic understanding of health.

PURPOSE: Frailty is characterised by decreased physiological reserves and vulnerability to stressors. Although scales, such as the Fried's Frailty Phenotype (FP), Frailty Index (FI), and Clinical Frailty Scale (CFS), are used to identify frailty, the lived experience of frailty remains understudied. METHODS: This cross-sectional observational research involved participants aged 65 years and older from Wave 1 of The Irish Longitudinal Study on Ageing (TILDA). Participants were categorised into four independent groups: three frail groups based on the aforementioned scales and a non-frail group. Quantitative variables, including self-rated health, CASP-19 quality-of-life score, and frequency of social activities, were analysed and described. RESULTS: The study encompassed 1999 participants with an average age of 72 years, of whom 51% were women. FP exclusively identified 1.6% as frail (n = 32), FI 11.7% (n = 233), and CFS 6.8% (n = 135). More than 60% of all those classified as frail reported their health as good, very good, or excellent, with the lowest proportion (64%) being among frail by FI participants. Frail by FI participants exhibited the lowest mean average CASP-19 score, yet it remained relatively high at 39 out of 57 points. Over 77% of all frail individuals engaged in active leisure activities at least once a month. CONCLUSION: This study underscores the need to comprehend frailty holistically beyond its mere identification. It challenges the prevailing belief that frailty inevitably leads to impaired quality of life and limited social engagement. The findings advocate for a reassessment of how both the general public and healthcare professionals perceive frailty.

Is a sex difference in audio-visual temporal precision consistent across age groups? An update on Hernández et al. (2019).

Hernández et al. (2019) previously reported independent age and sex differences in temporal audio-visual integration in a large national cohort of older adults. Susceptibility to the sound induced flash illusion (SIFI) at long stimulus onset asynchronies (SOAs) increased with age and was stronger in older adult females than males. However, it is unclear if this sex difference is stable across age. We reanalyzed the data set used by Hernández et al. (2019) on SIFI performance from 3,479 older adults (Mage = 64.20 years, SD = 7.77, range = 50-93; 56% female) across three age groups (50-64, 65-74, and 75+ years), drawn from The Irish Longitudinal Study on Ageing. For the 70 ms SOA, females were less susceptible to the SIFI than males, irrespective of age. At longer SOAs (150 ms and 230 ms), females aged 50-64 years but not older were more susceptible to the SIFI than age-matched males. These findings extend those of Hernández et al. (2019) by indicating that age and sex can collectively influence the precision of multisensory integration exhibited by older adults. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Physical activity dose for generalized anxiety disorder & worry: Results from the Irish longitudinal study on ageing.

The lowest moderate-to-vigorous physical activity (MVPA) dose that conveys protection for Generalized Anxiety Disorder (GAD) and worry is unknown. This study quantified associations of weekly accumulated MVPA doses with GAD and worry across 10 years using data from The Irish Longitudinal Study on Ageing (TILDA). Continuous MVPA (metabolic equivalent of task [MET] minutes per week [MET.min.week-1]; e.g., moderate-intensity brisk walking = 4METs), three-dose and, more precise, five-dose MVPA categories were examined. Worry symptoms and GAD status were measured using the Penn State Worry Questionnaire-Abbreviated and the Composite International Diagnostic Interview. Multivariable negative random effect binomial regression and logistic models adjusted for relevant covariates quantified associations across time. Among the 7,650 participants, compared to no MVPA (0 MET.min.week-1), 18 % (OR: 0.82; 95 %CI: [0.69-0.98]), 22 % (OR: 0.78; [ 0.64-0.95]) and 31 % (OR: 0.69; [0.59-0.79]) lower odds of GAD were found for the doses of 1-<600, 600-<1,200 and ≥2,400 MET.min.week-1 respectively. Post-hoc analysis demonstrated 47 % lower odds (OR: 0.53; (0.36-0.78) of GAD for 1-<200 MET.min.week1 compared to inactivity. Compared to no activity, engaging in even minimal physical activity equivalent of 10 min/day for five days/week of moderate-intensity activity (e.g., brisk walking), may lower the risk of GAD over time among older adults.

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.

Orthostatic Hypotension in Adults With Hypertension: A Scientific Statement From the American Heart Association.

Although orthostatic hypotension (OH) has long been recognized as a manifestation of autonomic dysfunction, a growing body of literature has identified OH as a common comorbidity of hypertension. This connection is complex, related to pathophysiology in blood pressure regulation and the manner by which OH is derived as the difference between 2 blood pressure measurements. While traditional therapeutic approaches to OH among patients with neurodegenerative disorders focus on increasing upright blood pressure to prevent cerebral hypoperfusion, the management of OH among patients with hypertension is more nuanced; resting hypertension is itself associated with adverse outcomes among these patients. Although there is substantial evidence that intensive blood pressure treatment does not cause OH in the majority of patients with essential hypertension, some classes of antihypertensive agents may unmask OH in patients with an underlying autonomic impairment. Practical steps to manage OH among adults with hypertension start with (1) a thorough characterization of its patterns, triggers, and cause; (2) review and removal of aggravating factors (often pharmacological agents not related to hypertension treatment); (3) optimization of an antihypertensive regimen; and (4) adoption of a tailored treatment strategy that avoids exacerbating hypertension. These strategies include countermaneuvers and short-acting vasoactive agents (midodrine, droxidopa). Ultimately, further research is needed on the epidemiology of OH, the impact of hypertension treatment on OH, approaches to the screening and diagnosis of OH, and OH treatment among adults with hypertension to improve the care of these patients and their complex blood pressure pathophysiology.

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.

Relationship between hippocampal subfield volumes and cognitive decline in healthy subjects.

We examined the relationship between hippocampal subfield volumes and cognitive decline over a 4-year period in a healthy older adult population with the goal of identifying subjects at risk of progressive cognitive impairment which could potentially guide therapeutic interventions and monitoring. 482 subjects (68.1 years +/- 7.4; 52.9% female) from the Irish Longitudinal Study on Ageing underwent magnetic resonance brain imaging and a series of cognitive tests. Using K-means longitudinal clustering, subjects were first grouped into three separate global and domain-specific cognitive function trajectories; High-Stable, Mid-Stable and Low-Declining. Linear mixed effects models were then used to establish associations between hippocampal subfield volumes and cognitive groups. Decline in multiple hippocampal subfields was associated with global cognitive decline, specifically the presubiculum (estimate -0.20; 95% confidence interval (CI) -0.78 - -0.02; p = 0.03), subiculum (-0.44; -0.82 - -0.06; p = 0.02), CA1 (-0.34; -0.78 - -0.02; p = 0.04), CA4 (-0.55; -0.93 - -0.17; p = 0.005), molecular layer (-0.49; -0.87 - -0.11; p = 0.01), dentate gyrus (-0.57; -0.94 - -0.19; p = 0.003), hippocampal tail (-0.53; -0.91 - -0.15; p = 0.006) and HATA (-0.41; -0.79 - -0.03; p = 0.04), with smaller volumes for the Low-Declining cognition group compared to the High-Stable cognition group. In contrast to global cognitive decline, when specifically assessing the memory domain, cornu ammonis 1 subfield was not found to be associated with low declining cognition (-0.14; -0.37 - 0.10; p = 0.26). Previously published data shows that atrophy of specific hippocampal subfields is associated with cognitive decline but our study confirms the same effect in subjects asymptomatic at time of enrolment. This strengthens the predictive value of hippocampal subfield atrophy in risk of cognitive decline and may provide a biomarker for monitoring treatment efficacy.

Can Artificial Intelligence Enhance Syncope Management?: A JACC: Advances Multidisciplinary Collaborative Statement.

Syncope, a form of transient loss of consciousness, remains a complex medical condition for which adverse cardiovascular outcomes, including death, are of major concern but rarely occur. Current risk stratification algorithms have not completely delineated which patients benefit from hospitalization and specific interventions. Patients are often admitted unnecessarily and at high cost. Artificial intelligence (AI) and machine learning may help define the transient loss of consciousness event, diagnose the cause, assess short- and long-term risks, predict recurrence, and determine need for hospitalization and therapeutic intervention; however, several challenges remain, including medicolegal and ethical concerns. This collaborative statement, from a multidisciplinary group of clinicians, investigators, and scientists, focuses on the potential role of AI in syncope management with a goal to inspire creation of AI-derived clinical decision support tools that may improve patient outcomes, streamline diagnostics, and reduce health-care costs.