RATIONALE:Speed of heart rate recovery (HRR) may serve as an important biomarker of aging and mortality.
OBJECTIVE:To examine whether the speed of HRR after an orthostatic maneuver (ie, active stand ...from supine position) predicts mortality.
METHODS AND RESULTS:A longitudinal cohort study involving a nationally representative sample of community-dwelling older individuals aged ≥50 years. A total of 4475 participants completed an active stand at baseline as part of a detailed clinic-based cardiovascular assessment. Beat-to-beat heart rate and blood pressure responses to standing were measured during a 2-minute window using a finometer and binned in 10-s intervals. We modeled HRR to the stand by age group, cardiovascular disease burden, and mortality status using a random effects model. Mortality status during a mean follow-up duration of 4.3 years served as the primary end point (n=138). Speed of HRR in the immediate 20 s after standing was a strong predictor of mortality. A 1-bpm slower HRR between 10 and 20 s after standing increased the hazard of mortality by 6% controlling for established risk factors. A clear dose–response relationship was evident. Sixty-nine participants in the slowest HRR quartile died during the observation period compared with 14 participants in the fastest HRR quartile. Participants in the slowest recovery quartile were 2.3× more likely to die compared with those in the fastest recovery quartile.
CONCLUSIONS:Speed of orthostatic HRR predicts mortality and may aid clinical decision making. Attenuated orthostatic HRR may reflect dysregulation of the parasympathetic branch of the autonomic nervous system.
To establish agreement between self-reported and actigraphy-based total sleep time (TST). To determine the impact of self-reported sleep problems on these measurements.
Cross-sectional study using ...data from Wave 3 of The Irish Longitudinal Study on Ageing (2014–2015).
Community-dwelling older adults, aged ≥50 years, with self-reported sleep information and ≥4 days of actigraphy-based TST (n = 1520).
Self-reported total sleep time, daytime sleepiness, insomnia symptoms (trouble falling asleep, trouble waking too early) measured during a structured self-interview. Actigraphy-based total TST was collected using GENEactiv wrist-worn accelerometers. Demographic characteristics and health information were controlled for. Analyses included descriptive statistics, reliability and agreement analysis using paired t-tests, intra-class correlations and Bland-Altman analysis. Linear regression was used to model associations with measurement discrepancies.
Participants reported that they slept 7.0 hours (SD: 1.4, Range: 2.0–13.0 hours) on average, compared to 7.7 hours (SD: 1.2 hours, Range: 3.0–13.0 hours) recorded by accelerometry. Trouble falling asleep or waking too early “most of the time” were associated with under-reporting of sleep by 2.3, and 2.2 hours respectively. Agreement between measurements had an intra-class correlation of 0.18 and wide 95% limits of agreement (-3.90 to 2.55 hours). Under-reporting of sleep was independently associated with insomnia symptoms.
The agreement between self-reported and actigraphy-based TST in community dwelling older adults was low. Self-reported insomnia symptoms were independently associated with under-reporting of sleep. Studies seeking to measure sleep duration should consider inclusion of questions measuring experience of insomnia symptoms to account for potential influence on measurements.
Access to affordable, objective and scalable biomarkers of brain function is needed to transform the healthcare burden of neuropsychiatric and neurodegenerative disease. Electroencephalography (EEG) ...recordings, both resting and in combination with targeted cognitive tasks, have demonstrated utility in tracking disease state and therapy response in a range of conditions from schizophrenia to Alzheimer's disease. But conventional methods of recording this data involve burdensome clinic visits, and behavioural tasks that are not effective in frequent repeated use. This paper aims to evaluate the technical and human-factors feasibility of gathering large-scale EEG using novel technology in the home environment with healthy adult users. In a large field study, 89 healthy adults aged 40–79 years volunteered to use the system at home for 12 weeks, 5 times/week, for 30 min/session. A 16-channel, dry-sensor, portable wireless headset recorded EEG while users played gamified cognitive and passive tasks through a tablet application, including tests of decision making, executive function and memory. Data was uploaded to cloud servers and remotely monitored via web-based dashboards. Seventy-eight participants completed the study, and high levels of adherence were maintained throughout across all age groups, with mean compliance over the 12-week period of 82% (4.1 sessions per week). Reported ease of use was also high with mean System Usability Scale scores of 78.7. Behavioural response measures (reaction time and accuracy) and EEG components elicited by gamified stimuli (P300, ERN, Pe and changes in power spectral density) were extracted from the data collected in home, across a wide range of ages, including older adult participants. Findings replicated well-known patterns of age-related change and demonstrated the feasibility of using low-burden, large-scale, longitudinal EEG measurement in community-based cohorts. This technology enables clinically relevant data to be recorded outside the lab/clinic, from which metrics underlying cognitive ageing could be extracted, opening the door to potential new ways of developing digital cognitive biomarkers for disorders affecting the brain.
Recent advances have enabled the creation of wireless, “dry” electroencephalography (EEG) recording systems, and easy-to-use engaging tasks, that can be operated repeatedly by naïve users, ...unsupervised in the home. Here, we evaluated the validity of dry-EEG, cognitive task gamification, and unsupervised home-based recordings used in combination. Two separate cohorts of participants—older and younger adults—collected data at home over several weeks using a wireless dry EEG system interfaced with a tablet for task presentation. Older adults (
n
= 50; 25 females; mean age = 67.8 years) collected data over a 6-week period. Younger male adults (
n
= 30; mean age = 25.6 years) collected data over a 4-week period. All participants were asked to complete gamified versions of a visual Oddball task and Flanker task 5–7 days per week. Usability of the EEG system was evaluated via participant adherence, percentage of sessions successfully completed, and quantitative feedback using the System Usability Scale. In total, 1,449 EEG sessions from older adults (mean = 28.9; SD = 6.64) and 684 sessions from younger adults (mean = 22.87; SD = 1.92) were collected. Older adults successfully completed 93% of sessions requested and reported a mean usability score of 84.5. Younger adults successfully completed 96% of sessions and reported a mean usability score of 88.3. Characteristic event-related potential (ERP) components—the P300 and error-related negativity—were observed in the Oddball and Flanker tasks, respectively. Using a conservative threshold for inclusion of artifact-free data, 50% of trials were rejected per at-home session. Aggregation of ERPs across sessions (2–4, depending on task) resulted in grand average signal quality with similar Standard Measurement Error values to those of single-session wet EEG data collected by experts in a laboratory setting from a young adult sample. Our results indicate that easy-to-use task-driven EEG can enable large-scale investigations in cognitive neuroscience. In future, this approach may be useful in clinical applications such as screening and tracking of treatment response.
Conduction along the optic nerve is often slowed in multiple sclerosis (MS). This is typically assessed by measuring the latency of the P100 component of the Visual Evoked Potential (VEP) using ...electroencephalography. The Visual Evoked Spread Spectrum Analysis (VESPA) method, which involves modulating the contrast of a continuous visual stimulus over time, can produce a visually evoked response analogous to the P100 but with a higher signal-to-noise ratio and potentially higher sensitivity to individual differences in comparison to the VEP. The main objective of the study was to conduct a preliminary investigation into the utility of the VESPA method for probing and monitoring visual dysfunction in multiple sclerosis. The latencies and amplitudes of the P100-like VESPA component were compared between healthy controls and multiple sclerosis patients, and multiple sclerosis subgroups. The P100-like VESPA component activations were examined at baseline and over a 3-year period. The study included 43 multiple sclerosis patients (23 relapsing-remitting MS, 20 secondary-progressive MS) and 42 healthy controls who completed the VESPA at baseline. The follow-up sessions were conducted 12 months after baseline with 24 MS patients (15 relapsing-remitting MS, 9 secondary-progressive MS) and 23 controls, and again at 24 months post-baseline with 19 MS patients (13 relapsing-remitting MS, 6 secondary-progressive MS) and 14 controls. The results showed P100-like VESPA latencies to be delayed in multiple sclerosis compared to healthy controls over the 24-month period. Secondary-progressive MS patients had most pronounced delay in P100-like VESPA latency relative to relapsing-remitting MS and controls. There were no longitudinal P100-like VESPA response differences. These findings suggest that the VESPA method is a reproducible electrophysiological method that may have potential utility in the assessment of visual dysfunction in multiple sclerosis.
Cognitive impairment (CI), often examined with neuropsychological tests such as the Paced Auditory Serial Addition Test (PASAT), affects approximately 65% of multiple sclerosis (MS) patients. The P3b ...event-related potential (ERP), evoked when an infrequent target stimulus is presented, indexes cognitive function and is typically compared across subjects' scalp electroencephalography (EEG) data. However, the clustering of independent components (ICs) is superior to scalp-based EEG methods because it can accommodate the spatiotemporal overlap inherent in scalp EEG data. Event-related spectral perturbations (ERSPs; event-related mean power spectral changes) and inter-trial coherence (ITCs; event-related consistency of spectral phase) reveal a more comprehensive overview of EEG activity. Ninety-five subjects (56 MS patients, 39 controls) completed visual and auditory two-stimulus P3b event-related potential tasks and the PASAT. MS patients were also divided into CI and non-CI groups (n = 18 in each) based on PASAT scores. Data were recorded from 128-scalp EEG channels and 4 IC clusters in the visual, and 5 IC clusters in the auditory, modality were identified. In general, MS patients had significantly reduced ERSP theta power versus controls, and a similar pattern was observed for CI vs. non-CI MS patients. The ITC measures were also significantly different in the theta band for some clusters. The finding that MS patients had reduced P3b task-related theta power in both modalities is a reflection of compromised connectivity, likely due to demyelination, that may have disrupted early processes essential to P3b generation, such as orientating and signal detection. However, for posterior sources, MS patients had a greater decrease in alpha power, normally associated with enhanced cognitive function, which may reflect a compensatory mechanism in response to the compromised early cognitive processing.
The heterogeneous specialisation of hippocampal subfields across memory functions has been widely shown in animal models. Yet, few in vivo studies in humans have explored correspondence between ...hippocampal subfield anatomy and memory performance in ageing. Here, we used a well-validated automated MR segmentation protocol to measure hippocampal subfield volumes in 436 non-demented adults aged 50+. We explored relationships between hippocampal subfield volume and verbal episodic memory, as indexed by word list recall at immediate presentation and following delay. In separate multilevel models for each task, we tested linearity and non-linearity of associations between recall performance and subfield volume. Fully-adjusted models revealed that immediate and delayed recall were both associated with cubic fits with respect to volume of subfields CA1, CA2/3, CA4, molecular layer, and granule cell layer of dentate gyrus; moreover, these effects were partly dissociable from quadratic age trends, observed for subiculum, molecular layer, hippocampal tail, and CA1. Furthermore, analyses of semantic fluency data revealed little evidence of robust associations with hippocampal subfield volumes. Our results show that specific hippocampal subfields manifest associations with memory encoding and retrieval performance in non-demented older adults; these effects are partly dissociable from age-related atrophy, and from retrieval of well-consolidated semantic categories.
Ageing is associated with widespread alterations to the brain's anatomy and to attendant cortical networks. Yet, few studies to date have indexed anatomical covariance network differences within the ...age distribution of older adulthood, despite known phenotypic variation. Here, we explored cortical anatomical covariance networks in middle and older age cross-sectionally, using a large sample of community-dwelling older adults from the Irish Longitudinal Study on Ageing (TILDA). We assayed age-related anatomical changes via cortical thickness. Moreover, we explored age-related alterations in small-world and global properties of cortical thickness covariance networks, by targeting analyses towards the elder (ages 75–88; n = 88) and younger (ages 52–64; n = 95) sample members. Age, sex, and chronic disease-adjusted vertex-wise analyses revealed robust reductions in cortical thickness with age. Graph theoretical analyses of cortical thickness covariance networks revealed significantly lower betweenness centrality (i.e., network hub status) at left inferior parietal cortex in the eldest participant group as compared to the youngest. Furthermore, indices of small-worldness revealed greater lambda (i.e., less effective integration) across the right hemisphere of the eldest participant group versus the youngest. Our results are interpreted in the context of mechanisms of cortical atrophy in ageing, functional network organisation, and cognition in ageing.
•We explored anatomical network differences in ageing via cortical thickness.•We examined age-related change in local and global network features with graph theory.•Left inferior parietal cortex's hub status was weaker in the over 75 s versus under 65 s.•Integration across the right hemisphere was lower in the over 75 s versus under 65 s.•Results are interpreted in light of cortical atrophy and functional network organisation.
Cerebral hypoperfusion is implicated in the pathogenesis of associations between orthostatic hypotension and adverse outcome such as falls, cognitive impairment, depression, and mortality. Although ...the blood pressure response to orthostasis has been well studied there is a lack of information on orthostatic cerebrovascular responses in older populations.
We measured cerebral hemodynamics, utilizing near infrared spectroscopy, coupled with peripheral blood pressure during an active stand in a large population of well-phenotyped older adults (N = 2764). Multi-level mixed effect models were utilized to investigate associations with age and sex, as well as confounders including anti-hypertensive medications. Normative cerebral oxygenation responses were also modelled utilizing generalized additive models for location, scale, and shape (GAMLSS). Older age groups experienced larger initial drops in oxygenation and a slower recovery, and responses also differed by sex. The drop after standing ranged from −1.85 % (95 % confidence interval (CI): −2.02 to −1.68) in the males aged 54–59 years vs −1.15 % (95 % CI: −1.31 to −1.00) in females aged 54–59 years, to −2.67 % (95 % CI: −3.01 to −2.33) in males aged ≥ 80 years vs −1.97 % (95 % CI: −2.32 to −1.62) females aged ≥ 80 years. Reduced oxygenation levels were also evident in those taking anti-hypertensive medications.
Cerebral autoregulation is impaired with age, particularly in older women and those taking anti-hypertensives. SBP during the stand explained some of the age gradient in the late recovery stage of the stand for the oldest age group. Reported orthostatic symptoms did not correlate with hypoperfusion. Therefore, measures of orthostatic cerebral flow should be assessed in addition to peripheral BP in older patients irrespective of symptoms. Further studies are required to investigate the relationship between NIRS measurements and clinical outcomes such as falls, cognitive impairment and depression.
•We profiled the cerebral oxygenation response to orthostasis in large well-described community-dwelling population, adjusting for a large number of confounders.•Older age groups had a larger initial drop in cerebral oxygenation and impaired stabilization.•Women experienced a smaller drop in oxygenation compared to men, but impaired stabilization was more marked in women.•Those treated with anti-hypertensive medications had deficits in recovery of cerebral oxygenation after standing.•Hypoperfusion did not correlate with reported orthostatic symptoms.
BACKGROUND—In this report, we provide the first normative reference data and prevalence estimates of impaired orthostatic blood pressure (BP) stabilization, initial orthostatic hypotension, and ...orthostatic hypotension based on beat-to-beat blood pressure methods in a population-representative sample.
METHODS AND RESULTS—Participants were recruited from a nationally representative cohort study (≥50 years). Beat-to-beat systolic BP, diastolic BP, and heart rate records were analyzed among those who underwent an active stand test (n=4475). Normograms were estimated by use of generalized additive models for location, shape, and scale with Box-Cox power exponential distribution. Prevalence estimates of impaired BP stabilization, initial orthostatic hypotension, and orthostatic hypotension are reported. Orthostatic BP responses in adults aged 50 to 59 years stabilized within 30 seconds of standing, with older groups taking 30 seconds or longer. The total prevalence of impaired BP stabilization was 15.6% (95% confidence interval CI, 14.1%–17.1%), increasing with age to 41.2% (95% CI, 30.0%–52.4%) in people ≥80 years old. Initial orthostatic hypotension occurred in 32.9% (95% CI, 31.2%–34.6%) of the population aged ≥50 years, with no age gradient evident. The prevalence of orthostatic hypotension was 6.9% (95% CI, 5.9%–7.8%) in the total population, increasing to 18.5% (95% CI, 9.0%–28.0%) in those aged ≥80 years old.
CONCLUSIONS—Significant age-related differences exist in the time course of postural BP responses, with abnormal responses taking longer than 30 seconds to stabilize. Impaired BP stabilization is more common as we age, affecting more than two-fifths of the population aged ≥80 years, and may play a future role in the management of falls and syncope.
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