How do predisposing factors differ between delirium motor subtypes? A systematic review and meta-analysis.

BACKGROUND: Delirium is a common neurocognitive disorder in hospitalised older adults with vast negative consequences. The predominant method of subtyping delirium is by motor activity profile into hypoactive, hyperactive and mixed groups. OBJECTIVE: This systematic review and meta-analysis investigated how predisposing factors differ between delirium motor subtypes. METHODS: Databases (Medline, PsycINFO, Embase) were systematically searched for studies reporting predisposing factors (prior to delirium) for delirium motor subtypes. A total of 61 studies met inclusion criteria (N = 14,407, mean age 73.63 years). Random-effects meta-analyses synthesised differences between delirium motor subtypes relative to 22 factors. RESULTS: Hypoactive cases were older, had poorer cognition and higher physical risk scores than hyperactive cases and were more likely to be women, living in care homes, taking more medications, with worse functional performance and history of cerebrovascular disease than all remaining subtypes. Hyperactive cases were younger than hypoactive and mixed subtypes and were more likely to be men, with better cognition and lower physical risk scores than all other subtypes. Those with no motor subtype (unable to be classified) were more likely to be women and have better functional performance. Effect sizes were small. CONCLUSIONS: Important differences in those who develop motor subtypes of delirium were shown prior to delirium occurrence. We provide robust quantitative evidence for a common clinical assumption that indices of frailty (institutional living, cognitive and functional impairment) are seen more in hypoactive patients. Motor subtypes should be measured across delirium research. Motor subtyping has great potential to improve the clinical risk assessment and management of delirium.

Increased postflight carotid artery stiffness and inflight insulin resistance resulting from 6-mo spaceflight in male and female astronauts.

Removal of the normal head-to-foot gravity vector and chronic weightlessness during spaceflight might induce cardiovascular and metabolic adaptations related to changes in arterial pressure and reduction in physical activity. We tested hypotheses that stiffness of arteries located above the heart would be increased postflight, and that blood biomarkers inflight would be consistent with changes in vascular function. Possible sex differences in responses were explored in four male and four female astronauts who lived on the International Space Station for 6 mo. Carotid artery distensibility coefficient (P = 0.005) and ß-stiffness index (P = 0.006) reflected 17-30% increases in arterial stiffness when measured within 38 h of return to Earth compared with preflight. Spaceflight-by-sex interaction effects were found with greater changes in ß-stiffness index in women (P = 0.017), but greater changes in pulse wave transit time in men (P = 0.006). Several blood biomarkers were changed from preflight to inflight, including an increase in an index of insulin resistance (P < 0.001) with a spaceflight-by-sex term suggesting greater change in men (P = 0.034). Spaceflight-by-sex interactions for renin (P = 0.016) and aldosterone (P = 0.010) indicated greater increases in women than men. Six-month spaceflight caused increased arterial stiffness. Altered hydrostatic arterial pressure gradients as well as changes in insulin resistance and other biomarkers might have contributed to alterations in arterial properties, including sex differences between male and female astronauts.

Characterization of internal jugular vein region-specific distension and flow patterns during progressive volume shifting.

Blood volume shifts during postural adjustment lead to irregular distension of the internal jugular vein (IJV). In microgravity, distension may contribute to flow stasis and thromboembolism, though the regional implications and associated risk remain unexplored. We characterized regional differences in IJV volume distension and flow complexity during progressive head-down tilt (HDT) (0°, -6°, -15°, -30°) using conventional ultrasound and vector flow imaging. We also evaluated low-pressure thigh cuffs (40 mmHg) as a fluid shifting countermeasure during -6° HDT. Total IJV volume expanded 139 ± 95% from supine position (4.6 ± 2.7 mL) to -30° HDT (10.3 ± 5.0 mL). Blood flow profiles had greater vector uniformity at the cranial IJV region (P < 0.01) and became more dispersed with increasing tilt (P < 0.01). Qualitatively, flow was more uniform throughout the IJV during its early flow cycle phase and more disorganized during late flow phase. This disorganized flow was accentuated closer to the vessel wall, near the caudal region, and during greater HDT. Low-pressure thigh cuffs during -6° HDT decreased IJV volume at the cranial region (-12 ± 15%; P < 0.01) but not the caudal region (P = 0.20), although flow uniformity was unchanged (both regions, P > 0.25). We describe a distensible IJV accommodating large volume shifts along its length. Prominent flow dispersion was primarily found at the caudal region, suggesting multidirectional blood flow. Thigh cuffs appear effective for decreasing IJV volume but effects on flow complexity are minor. Flow complexity along the vessel length is likely related to IJV distension during chronic volume shifting and may be a precipitating factor for flow stasis and future thromboembolism risk.NEW & NOTEWORTHY The internal jugular vein (IJV) facilitates cerebral outflow and is sensitive to volume shifts. Concerns about IJV expansion and fluid flow behavior in astronauts have surfaced following thromboembolism reports. Our study explored regional volume distension and blood flow complexity in the IJV during progressive volume shifting. We observed stepwise volume distension and increasing flow dispersion with head-down tilting across all regions. Flow dispersion may pose a risk of future thromboembolism during prolonged volume shifts.

Systematic review of the use of ultrasound for venous assessment and venous thrombosis screening in spaceflight.

The validity of venous ultrasound (V-US) for the diagnosis of deep vein thrombosis (DVT) during spaceflight is unknown and difficult to establish in diagnostic accuracy and diagnostic management studies in this context. We performed a systematic review of the use of V-US in the upper-body venous system in spaceflight to identify microgravity-related changes and the effect of venous interventions to reverse them, and to assess appropriateness of spaceflight V-US with terrestrial standards. An appropriateness tool was developed following expert panel discussions and review of terrestrial diagnostic studies, including criteria relevant to crew experience, in-flight equipment, assessment sites, ultrasound modalities, and DVT diagnosis. Microgravity-related findings reported as an increase in internal jugular vein (IJV) cross-sectional area and pressure were associated with reduced, stagnant, and retrograde flow. Changes were on average responsive to venous interventions using lower body negative pressure, Bracelets, Valsalva and Mueller manoeuvres, and contralateral IJV compression. In comparison with terrestrial standards, spaceflight V-US did not meet all appropriateness criteria. In DVT studies (n = 3), a single thrombosis was reported and only ultrasound modality criterion met the standards. In the other studies (n = 15), all the criteria were appropriate except crew experience criterion, which was appropriate in only four studies. Future practice and research should account for microgravity-related changes, evaluate individual effect of venous interventions, and adopt Earth-based V-US standards.

Motorized 3D Ultrasound and Jugular Vein Dimension Measurement on the International Space Station.

BACKGROUND: Internal jugular vein (IJV) congestion occurs during spaceflight. Historically, IJV distension on the International Space Station (ISS) has been quantified using single slice cross-sectional images from conventional 2D ultrasound with remote guidance. Importantly, the IJV is an irregular shape and highly compressible. Consequently, conventional imaging is susceptible to poor reproducibility due to inconsistent positioning, insonation angle, and hold-down pressure, especially when controlled by novice sonographers (i.e., astronauts). Recently, a motorized 3D ultrasound was launched to the ISS that mitigates angulation errors and has a larger design, allowing for more consistent hold-down pressure and positioning. This short communication compares IJV congestion measured with 2D vs. 3D methods during spaceflight.METHODS: IJV was measured prior to and following a 4-h venoconstrictive thigh cuff countermeasure. Data were acquired from three astronauts approximately halfway through their 6-mo missions.RESULTS: The 2D and 3D ultrasound results were not congruent in all astronauts. 3D ultrasound confirmed that the countermeasure reduced IJV volume in three astronauts by approximately 35%, whereas 2D data were more equivocal. These results indicate that 3D ultrasound provides less error-prone quantitative data.DISCUSSION: These data are the first to compare 2D and 3D methods during spaceflight in the same participants by using a known countermeasure that reduces IJV congestion. The current results demonstrate that 3D ultrasound should be the preferred imaging method when trying to measure venous congestion in the IJV, and that 2D ultrasound results should be interpreted with caution.Patterson C, Greaves DK, Robertson A, Hughson R, Arbeille PL. Motorized 3D ultrasound and jugular vein dimension measurement on the International Space Station. Aerosp Med Hum Perform. 2023; 94(6):466-469.

Resting EEG power spectra across middle to late life: associations with age, cognition, APOE-ɛ4 carriage, and cardiometabolic burden.

We investigated how resting electroencephalography (EEG) measures are associated with risk factors for late-life cognitive impairment and dementia, including age, apolipoprotein E ɛ4 (APOE-ɛ4) carriage, and cardiometabolic burden. Resting EEG was recorded from 86 adults (50-80 years of age). Participants additionally completed the Addenbrooke's Cognitive Examination (ACE) III and had blood drawn to assess APOE-ɛ4 carriage status and cardiometabolic burden. EEG power spectra were decomposed into sources of periodic and aperiodic activity to derive measures of aperiodic component slope and alpha (7-14 Hz) and beta (15-30 Hz) peak power and peak frequency. Alpha and beta peak power measures were corrected for aperiodic activity. The aperiodic component slope was correlated with ACE-III scores but not age. Alpha peak frequency decreased with age. Individuals with higher cardiometabolic burden had lower alpha peak frequencies and lower beta peak power. APOE-ɛ4 carriers had lower beta peak frequencies. Our findings suggest that the slope of the aperiodic component of resting EEG power spectra is more closely associated with measures of cognitive performance rather than chronological age in older adults.

The effects of computerised cognitive training on post-CABG delirium and cognitive change: A prospective randomised controlled trial.

Background: Cognitive impairments, including delirium, are common after coronary artery bypass grafting (CABG). Improving cognition pre- and post-operatively using computerised cognitive training (CCT) may be an effective approach to improve cognitive outcomes in CABG patients. Objectives: Investigate the effect of remotely supervised CCT on cognitive outcomes, including delirium, in older adults undergoing CABG surgery. Methods: Thirty-six participants, were analysed in a single-blinded randomised controlled trial (CCT Intervention: n = 18, Control: n = 18). CCT was completed by the intervention group pre-operatively (every other day, 45-60-minute sessions until surgery) and post-operatively, beginning 1-month post-CABG (3 x 45-60-minute sessions/week for 12-weeks), while the control group maintained usual care plus weekly phone calls. Cognitive assessments were conducted pre- and post-operatively at multiple follow-ups (discharge, 4-months and 6-months). Post-operative delirium incidence was assessed daily until discharge. Cognitive change data were calculated at each follow-up for each cognitive test (Addenbrooke's Cognitive Examination III and CANTAB; z-scored). Results: Adherence to the CCT intervention (completion of three pre-operative or 66% of post-operative sessions) was achieved in 68% of pre-CABG and 59% of post-CABG participants. There were no statistically significant effects of CCT on any cognitive outcome, including delirium incidence. Conclusion: Adherence to the CCT program was comparatively higher than previous feasibility studies, possibly due to the level of supervision and support provided (blend of face-to-face and home-based training, with support phone calls). Implementing CCT interventions both pre- and post-operatively is feasible in those undergoing CABG. No statistically significant benefits from the CCT interventions were identified for delirium or cognitive function post-CABG, likely due to the sample size available (study recruitment greatly impacted by COVID-19). It also may be the case that multimodal intervention would be more effective.

Effects of whole-body vibration or resistive-vibration exercise on blood clotting and related biomarkers: a systematic review.

Whole-body vibration (WBV) and resistive vibration exercise (RVE) are utilized as countermeasures against bone loss, muscle wasting, and physical deconditioning. The safety of the interventions, in terms of the risk of inducing undesired blood clotting and venous thrombosis, is not clear. We therefore performed the present systematic review of the available scientific literature on the issue. The review was conducted following the guidelines by the Space Biomedicine Systematic Review Group, based on Cochrane review guidelines. The relevant context or environment of the studies was "ground-based environment"; space analogs or diseased conditions were not included. The search retrieved 801 studies; 77 articles were selected for further consideration after an initial screening. Thirty-three studies met the inclusion criteria. The main variables related to blood markers involved angiogenic and endothelial factors, fibrinolysis and coagulation markers, cytokine levels, inflammatory and plasma oxidative stress markers. Functional and hemodynamic markers involved blood pressure measurements, systemic vascular resistance, blood flow and microvascular and endothelial functions. The available evidence suggests neutral or potentially positive effects of short- and long-term interventions with WBV and RVE on variables related to blood coagulation, fibrinolysis, inflammatory status, oxidative stress, cardiovascular, microvascular and endothelial functions. No significant warning signs towards an increased risk of undesired clotting and venous thrombosis were identified. If confirmed by further studies, WBV and RVE could be part of the countermeasures aimed at preventing or attenuating the muscular and cardiovascular deconditioning associated with spaceflights, permanence on planetary habitats and ground-based simulations of microgravity.

Pathophysiology, risk, diagnosis, and management of venous thrombosis in space: where are we now?

The recent incidental discovery of an asymptomatic venous thrombosis (VT) in the internal jugular vein of an astronaut on the International Space Station prompted a necessary, immediate response from the space medicine community. The European Space Agency formed a topical team to review the pathophysiology, risk and clinical presentation of venous thrombosis and the evaluation of its prevention, diagnosis, mitigation, and management strategies in spaceflight. In this article, we discuss the findings of the ESA VT Topical Team over its 2-year term, report the key gaps as we see them in the above areas which are hindering understanding VT in space. We provide research recommendations in a stepwise manner that build upon existing resources, and highlight the initial steps required to enable further evaluation of this newly identified pertinent medical risk.

Short-term variability of blood pressure: effects of lower-body negative pressure and long-duration bed rest.

Mild lower-body negative pressure (LBNP) has been utilized to selectively unload cardiopulmonary baroreceptors, but there is evidence that arterial baroreceptors can be transiently unloaded after the onset of mild LBNP. In this paper, a black box mathematical model for the prediction of diastolic blood pressure (DBP) variability from multiple inputs (systolic blood pressure, R-R interval duration, and central venous pressure) was applied to interpret the dynamics of blood pressure maintenance under the challenge of LBNP and in long-duration, head-down bed rest (HDBR). Hemodynamic recordings from seven participants in the WISE (Women's International Space Simulation for Exploration) Study collected during an experiment of incremental LBNP (-10 mmHg, -20 mmHg, -30 mmHg) were analyzed before and on day 50 of a 60-day-long HDBR campaign. Autoregressive spectral analysis focused on low-frequency (LF, ~0.1 Hz) oscillations of DBP, which are related to fluctuations in vascular resistance due to sympathetic and baroreflex regulation of vasomotor tone. The arterial baroreflex-related component explained 49 ± 13% of LF variability of DBP in spontaneous conditions, and 89 ± 9% (P < 0.05) on day 50 of HDBR, while the cardiopulmonary baroreflex component explained 17 ± 9% and 12 ± 4%, respectively. The arterial baroreflex-related variability was significantly increased in bed rest also for LBNP equal to -20 and -30 mmHg. The proposed technique provided a model interpretation of the proportional effect of arterial baroreflex vs. cardiopulmonary baroreflex-mediated components of blood pressure control and showed that arterial baroreflex was the main player in the mediation of DBP variability. Data during bed rest suggested that cardiopulmonary baroreflex-related effects are blunted and that blood pressure maintenance in the presence of an orthostatic stimulus relies mostly on arterial control.

Heart rate and daily physical activity with long-duration habitation of the International Space Station.

INTRODUCTION: We investigated the pattern of activity and heart rate (HR) during daily living on the International Space Station (ISS) compared to on Earth in 7 long-duration astronauts to test the hypotheses that the HR responses on the ISS would be similar to preflight values, although the pattern of activity would shift to a dominance of arm activity, and postflight HR would be elevated compared to preflight during similar levels of activity. METHODS: HR and ankle and wrist activity collected for 24-h periods before, during, and after spaceflight were divided into night, morning, afternoon, and evening segments. Exercise was excluded and analyzed separately. RESULTS: Consistent with the hypotheses, HR during daily activities on the ISS was unchanged compared to preflight; activity patterns shifted to predominantly arm in space. Contrary to the hypothesis, only night time HR was elevated postflight, although this was very small (+4 +/- 3 bpm compared to preflight). A trend was found for higher postflight HR in the afternoon (+10 +/- 10 bpm) while ankle activity level was not changed (99 +/- 48, 106 +/- 52 counts pre- to postflight, respectively). Astronauts engaged in aerobic exercise 4-8 times/week, 30-50 min/session, on a cycle ergometer and treadmill. Resistance exercise sessions were completed 4-6 times/week for 58 +/- 14 min/session. DISCUSSION: Astronauts on ISS maintained their HR during daily activities; on return to Earth there were only very small increases in HR, suggesting that cardiovascular fitness was maintained to meet the demands of normal daily activities.

4 days in dry immersion increases arterial wall response to ultrasound wave as measured using radio-frequency signal, comparison with spaceflight data.

Recent studies have reported a significant increase in common carotid artery (CCA) intima media thickness, wall stiffness and reflectivity to ultrasound, in astronauts, after six months of spaceflight. The hypothesis was that 4 days in dry immersion (subjects under bags of water) will be sufficient to change the CCA wall reflectivity to ultrasound similar to what observed after spaceflight. Such response would be quantified using the amplitude of the ultrasound signal returned to the probe by the target concerned. [coefficient of signal return (Rs)]. The Rs for anterior and posterior CCA wall, sternocleidomastoid muscle, intima layer and CCA lumen were calculated from the ultrasound radio frequency (RF) data displayed along each echographic line. After four days of DI, Rs increased in the CCA posterior wall (+15% +/- 10 from pre DI, p < 0.05), while no significant change was observed in the other targets. The observed increase in Rs with DI was approximately half compared to what was observed after six months of space flight (+34% +/- 14). This difference may be explained by dose response (dry immersion only four days in duration). As a marker of tissue-level physical changes, Rs provide complimentary information alongside previously observed CCA wall thickness and stiffness.

Does APOE ɛ4 Status Change How 24-Hour Time-Use Composition Is Associated with Cognitive Function? An Exploratory Analysis Among Middle-to-Older Adults.

BACKGROUND: The 24 h time-use composition of physical activity, sedentary behavior, and sleep is linked to cognitive function in adults and may contribute to future dementia risk. However, the impact of reallocating time between behaviors may differ depending on an individual's genetic dementia risk. OBJECTIVE: To explore if there is an interaction between 24 h time-use composition and genetic dementia risk in relation to cognitive function, and to simulate how time-reallocations are associated with cognitive function across different levels of genetic dementia risk. METHODS: Cross-sectional global cognition, executive function, genetic dementia risk (at least one apolipoprotein (APOE) ɛ4 allele versus none) and 7 days of 24 h accelerometry (average daily time-use composition of moderate-to-vigorous physical activity (MVPA), light physical activity, sedentary behavior, sleep) were collected from 82 adults (65.6±7.5 years, 49 females). Linear regression was used to explore the relationship between time-use composition and cognitive measures, testing for interaction between APOE ɛ4 status and time-use composition. The models were used to simulate time reallocations in both APOE ɛ4 status groups. RESULTS: The 24 h time-use composition was associated with global cognition (F = 2.4, p = 0.02) and executive function (F = 2.6, p = 0.01). For both measures, the association differed according to genetic risk (interactions p < 0.001). In both APOE groups, reallocating time to MVPA was beneficially associated with measures of cognitive function, but associations were larger among those with at least one APOE ɛ4 allele. CONCLUSION: Genetic dementia risk may impact the effectiveness of activity interventions. Increasing MVPA may provide greater benefits among those with higher genetic dementia risk.

4 Day in dry immersion reproduces partially the aging effect on the arteries as observed during 6 month spaceflight or confinement.

The objectives of this study were to determine whether 4 days of dry immersion (DI) induced similar arterial aging as spaceflight and to test the impact of thigh cuffs. Eighteen subjects underwent DI; nine wore thigh cuffs. Cardiac and arterial targets were assessed by ultrasound. No significant differences were found between the groups. The left ventricle volume, stroke volume (SV), and ejection fraction decreased with DI (p < 0.001). Carotid distensibility reduced (p < 0.05), carotid to femoral arterial tree became stiffer in 33% of the subjects, and femoral artery intima media thickness increased (p < 0.05). A reduction in plasma volume is likely to have caused the observed cardiac changes, whereas the arterial wall changes are probably best explained by hypokinesia and/or environmental stress. These changes are similar but lower in amplitude than those observed in spaceflight and mimic the natural aging effect on earth. The daytime-worn thigh cuffs had no acute or chronic impact on these arterial-focused measurements.

Index of Reflectivity of Ultrasound Radio Frequency Signal from the Carotid Artery Wall Increases in Astronauts after a 6 mo Spaceflight.

The objective was to quantify the index of reflectivity of the common carotid artery and surrounding structures, before and after 6 mo of microgravity. Our hypothesis was that structural changes in the insonated target would increase its index of reflectivity. The neck anterior muscle and common carotid artery (walls and lumen) were visualized by echography (17 MHz linear probe), and the radiofrequency signal along each vertical line was displayed. The limits of the radiofrequency data corresponding to each target (muscle, vessel wall) were determined from the B-mode image and radiofrequency trace. Each target's index of reflectivity was calculated as the proportion of backscattered energy to the whole backscattered energy along the line. After 6 mo in flight, the index of reflectivity increased significantly for both common carotid walls, while it remained unchanged for the neck muscle, carotid intima and lumen. The index of reflectivity provided additional information beyond traditional B-mode imaging.

WISE-2005: prolongation of left ventricular pre-ejection period with 56 days head-down bed rest in women.

This study tested the hypothesis that prolonged physical deconditioning affects the coupling of left ventricular depolarization to its ejection (the pre-ejection period, PEPi) and that this effect is minimized by exercise countermeasures. Following assignment to non-exercise (Control) and exercise groups (Exercise), 14 females performed 56 days of continuous head-down tilt bed rest. Measurements of the electrocardiogram (ECG) and stroke volume (Doppler ultrasound) during supine rest were obtained at baseline prior to (Pre) and after (Post) the head-down tilt bed rest (HDBR) period. Compared with Pre, the PEPi was increased following head-down tilt bed rest (main effect, P < 0.005). This effect was most dominant in the Control group [Pre = 0.038 ± 0.06 s (s.d.) versus Post = 0.054 ± 0.011 s; P < 0.001]. In the Exercise group, PEPi was 0.032 ± 0.005 s Pre and 0.038 ± 0.018 s Post; P= 0.08. Neither the QRS interval nor cardiac afterload was modified by head-down tilt bed rest in Control or Exercise groups. Low-dose isoprenaline infusion reversed the head-down tilt bed rest-induced delay in the PEPi. These results suggest that head-down tilt bed rest leads to a delayed onset of systolic ejection following left ventricular depolarization in a manner that is affected little by the exercise countermeasure but is related to ß-adrenergic pathways. The delayed onset of systole following head-down tilt bed rest appears to be related to mechanism(s) affecting contraction of the left ventricle rather than its depolarization.

Thigh Cuff Effects on Venous Flow Redistribution During 4 Days in Dry Immersion.

PURPOSE: The objective was to quantify the venous redistribution during a 4-d dry immersion (DI) and evaluate the effect of thigh cuffs.METHODS: The study included nine control (Co) and nine subjects wearing thigh cuffs during the daytime (CU). Ultrasound measures were performed Pre-DI, on day 4 AM (D4 AM) and D4 PM: left ventricle stroke volume and ejection fraction (SV, EF), jugular vein volume (JVvol), portal vein diameter (PV), and middle cerebral vein velocity (MCVv). An additional measure of JVvol was performed on Day 1 after 2 h in DI.RESULTS: After 2 h in DI, JVvol increased significantly from Pre in both groups, but increased more in the Co compared to the CU subjects (Co: 0.27 0.15 cm³ to 0.94 0.22 cm³; CU: 0.32 0.13 cm³ to 0.64 0.32 cm³). At D4 AM, SV and EF decreased from Pre (SV: 111 23 cm³ to 93 24 cm³; EF: 0.66 0.07 to 0.62 0.07). JVvol was slightly increased (Co: 0.47 0.22 cm³ CU: 0.35 014 cm³). MCVv and PV remained unchanged from Pre-DI. No difference was found between the two groups for any of the parameters measured. From D4 AM to PM, no significant change was observed for any parameter.CONCLUSION: The results confirm that DI induces, during the first 2-3 h, a significant cephalic fluid shift as observed in spaceflight. During this early phase, the thigh cuffs reduced the amplitude of the fluid shift toward the head, but after 4 d in DI there was only a slight memory (residual) effect of DI on the jugular volume and no residual effect of the thigh cuffs.Arbeille P, Greaves D, Guillon L, Besnard S. Thigh cuff effects on venous flow redistribution during 4 days in dry immersion. Aerosp Med Hum Perform. 2020; 91(9):697702.

Increasing Objective Cardiometabolic Burden Associated With Attenuations in the P3b Event-Related Potential Component in Older Adults.

Cardiometabolic diseases and risk factors increase the risk of late-life cognitive impairment and dementia and have also been associated with detrimental gray and white matter changes. However, the functional brain changes associated with cardiometabolic health in late-life are unclear. We sought to characterize these functional changes by recording event-related potentials (ERPs) during an n-back working memory task (0, 1, and 2 back) in 85 adults (60% female) between 50 and 80 years of age. Due to a stratified recruitment approach, participants varied widely in relation to cognitive function and cardiometabolic health. Standard and objective cut-offs for high blood glucose, waist to hip ratio (i.e., obesity), high blood cholesterol, and hypertension were employed to generate a summative score for cardiometabolic burden (none, one, or two or more above cut-off). Mixed effects modeling (covarying for age and gender) revealed no statistically significant associations between cardiometabolic burden and visual P1 and N1 component amplitudes. There was a significant effect for the P3b component: as cardiometabolic burden increased, P3b amplitude decreased. We show that cardiometabolic factors related to the development of cognitive impairment and dementia in late-life associate with brain activity, as recorded via ERPs. Findings have relevance for the monitoring of lifestyle interventions (typically targeting cardiometabolic factors) in aging, as ERPs may provide a more sensitive measure of change than cognitive performance. Further, our results raise questions related to the findings of a broad range of ERP studies where the groups compared may differ in their cardiometabolic health status (not only in psychological symptomatology).

Risk Factors for Delirium and Cognitive Decline Following Coronary Artery Bypass Grafting Surgery: A Systematic Review and Meta-Analysis.

Background Coronary artery bypass grafting (CABG) is known to improve heart function and quality of life, while rates of surgery-related mortality are low. However, delirium and cognitive decline are common complications. We sought to identify preoperative, intraoperative, and postoperative risk or protective factors associated with delirium and cognitive decline (across time) in patients undergoing CABG. Methods and Results We conducted a systematic search of Medline, PsycINFO, EMBASE, and Cochrane (March 26, 2019) for peer-reviewed, English publications reporting post-CABG delirium or cognitive decline data, for at least one risk factor. Random-effects meta-analyses estimated pooled odds ratio for categorical data and mean difference or standardized mean difference for continuous data. Ninety-seven studies, comprising data from 60 479 patients who underwent CABG, were included. Moderate to large and statistically significant risk factors for delirium were as follows: (1) preoperative cognitive impairment, depression, stroke history, and higher European System for Cardiac Operative Risk Evaluation (EuroSCORE) score, (2) intraoperative increase in intubation time, and (3) postoperative presence of arrythmia and increased days in the intensive care unit; higher preoperative cognitive performance was protective for delirium. Moderate to large and statistically significant risk factors for acute cognitive decline were as follows: (1) preoperative depression and older age, (2) intraoperative increase in intubation time, and (3) postoperative presence of delirium and increased days in the intensive care unit. Presence of depression preoperatively was a moderate risk factor for midterm (1-6 months) post-CABG cognitive decline. Conclusions This meta-analysis identified several key risk factors for delirium and cognitive decline following CABG, most of which are nonmodifiable. Future research should target preoperative risk factors, such as depression or cognitive impairment, which are potentially modifiable. Registration URL: https://www.crd.york.ac.uk/prosp​ero/; Unique identifier: CRD42020149276.

Computerised cognitive training to improve cognition including delirium following coronary artery bypass grafting surgery: protocol for a blinded randomised controlled trial.

INTRODUCTION: Coronary artery bypass grafting (CABG) surgery is known to improve vascular function and cardiac-related mortality rates; however, it is associated with high rates of postoperative cognitive decline and delirium. Previous attempts to prevent post-CABG cognitive decline using pharmacological and surgical approaches have been largely unsuccessful. Cognitive prehabilitation and rehabilitation are a viable yet untested option for CABG patients. We aim to investigate the effects of preoperative cognitive training on delirium incidence, and preoperative and postoperative cognitive training on cognitive decline at 4 months post-CABG. METHODS AND ANALYSIS: This study is a randomised, single-blinded, controlled trial investigating the use of computerised cognitive training (CCT) both pre-CABG and post-CABG (intervention group) compared with usual care (control group) in older adults undergoing CABG in Adelaide, South Australia. Those in the intervention group will complete 1-2 weeks of CCT preoperatively (45-60 min sessions, 3.5 sessions/week) and 12 weeks of CCT postoperatively (commencing 1 month following surgery, 45-60 min sessions, 3 sessions/week). All participants will undergo cognitive testing preoperatively, over their hospital stay including delirium, and postoperatively for up to 1 year. The primary delirium outcome variable will be delirium incidence (presence vs absence); the primary cognitive decline variable will be at 4 months (significant decline vs no significant decline/improvement from baseline). Logistic regression modelling will be used, with age and gender as covariates. Secondary outcomes include cognitive decline from baseline to discharge, and at 6 months and 1 year post-CABG. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Central Adelaide Local Health Network Human Research Ethics Committee (South Australia, Australia) and the University of South Australia Human Ethics Committee, with original approval obtained on 13 December 2017. It is anticipated that approximately two to four publications and multiple conference presentations (national and international) will result from this research. TRIAL REGISTRATION NUMBER: This clinical trial is registered with the Australian New Zealand Clinical Trials Registry and relates to the pre-results stage. Registration number: ACTRN12618000799257.