Cytochrome P450-soluble epoxide hydrolase derived linoleic acid oxylipins and cognitive performance in type 2 diabetes.

Type 2 diabetes mellitus (T2DM) increases the risk of cognitive decline and dementia. Disruptions in the cytochrome P450-soluble epoxide hydrolase (CYP450-sEH) pathway have been reported in T2DM, obesity and cognitive impairment. We examine linoleic acid (LA)-derived CYP450-sEH oxylipins and cognition in T2DM and explore potential differences between obese and nonobese individuals. The study included 51 obese and 57 nonobese participants (mean age 63.0 ± 9.9, 49% women) with T2DM. Executive function was assessed using the Stroop Color-Word Interference Test, FAS-Verbal Fluency Test, Digit Symbol Substitution Test, and Trails Making Test-Part B. Verbal memory was assessed using the California Verbal Learning Test, second Edition. Four LA-derived oxylipins were analyzed by ultra-high-pressure-LC/MS, and the 12,13-dihydroxyoctadecamonoenoic acid (12,13-DiHOME) considered the main species of interest. Models controlled for age, sex, BMI, glycosylated hemoglobin A1c, diabetes duration, depression, hypertension, and education. The sEH-derived 12,13-DiHOME was associated with poorer executive function scores (F1,98 = 7.513, P = 0.007). The CYP450-derived 12(13)-epoxyoctadecamonoenoic acid (12(13)-EpOME) was associated with poorer executive function and verbal memory scores (F1,98 = 7.222, P = 0.008 and F1,98 = 4.621, P = 0.034, respectively). There were interactions between obesity and the 12,13-DiHOME/12(13)-EpOME ratio (F1,97 = 5.498, P = 0.021) and between obesity and 9(10)-epoxyoctadecamonoenoic acid (9(10)-EpOME) concentrations (F1,97 = 4.126, P = 0.045), predicting executive function such that relationships were stronger in obese individuals. These findings suggest that the CYP450-sEH pathway as a potential therapeutic target for cognitive decline in T2DM. For some markers, relationships may be obesity dependent.

Acute physiological responses to high-intensity interval exercise in patients with coronary artery disease.

PURPOSE: Time spent closer to maximal effort during exercise is a potent stimulus for cardiorespiratory adaptations. The primary purpose was to determine which high-intensity interval exercise (HIIE) protocol provided the greatest physiological stimulus by comparing time spent ≥ 90% peak oxygen consumption (V̇O2peak) and heart rate reserve (HRR) in patients with coronary artery disease (CAD) in response to 3 HIIE protocols and the exercise standard of care, moderate-intensity continuous exercise (MICE). A secondary purpose was to assess protocol preference. METHODS: Fifteen patients with CAD (6 females, 67 ± 6 years) underwent measurements of V̇O2 and heart rate during MICE and three HIIE protocols all performed on a treadmill. The HIIE protocols included one with long intervals (4 × 4-min), short intervals (10 × 1-min), and an adapted version of the 4 × 4 [Toronto Rehabilitation Institute Protocol, (TRIP)]. Time spent ≥ 90% V̇O2peak and HRR were compared. RESULTS: Time spent ≥ 90% V̇O2peak was higher during 4 × 4 (6.3 ± 8.4 min) vs. MICE (1.7 ± 3.9 min; P = 0.001), while time spent ≥ 90% HRR was higher during 4 × 4 (6.0 ± 5.3 min) vs. MICE (0.1 ± 0.2 min; P < 0.001) and 10 × 1 (0.7 ± 0.8 min; P = 0.016). TRIP had similar responses as 10 × 1 and MICE. The 10 × 1 was the most preferred protocol and the 4 × 4 was the least preferred protocol. CONCLUSION: Longer intervals (4 × 4) provided the greatest physiological stimulus compared to the exercise standard of care and shorter intervals. However, this protocol was least preferred which may impact exercise adherence. Although the physiological stimulus is important to maximize training adaptations, exercise preferences and attitudes should be considered.

Capturing the perspectives of women with coronary artery disease regarding interval training or continuous exercise in cardiac rehabilitation.

BACKGROUND: Motivators and barriers to exercise participation in women with coronary artery disease remain poorly understood. With evidence suggesting that women with coronary artery disease are less likely to adhere to exercise during cardiac rehabilitation and are more likely to drop out, it is important to understand these factors in order to optimize cardiac rehabilitation programs for women. METHODS: We contribute to the discussion by presenting findings from a qualitative study using two focus groups with nine women with coronary artery disease sharing their experiences with attending cardiac rehabilitation and exercising in this setting, in addition to their perceived motivators and barriers to performing aerobic interval training. Focus group transcripts were analysed using a deductive thematic approach with Bandura's Social Cognitive Theory as the guiding conceptual framework. RESULTS: Four themes were identified regarding the attitudes and experiences of attending and exercising at cardiac rehabilitation, while five themes capturing the motivators and barriers for these women to perform aerobic interval training were identified for the first time. These novel themes encompassed the daunting nature of it, the physical discomfort associated with it, and conversely, the potential sense of enjoyment and accomplishment that it could bring. CONCLUSION: This study demonstrates the complexity of implementation of aerobic interval training into clinical practice, and suggests that further research is warranted to explore this domain.IMPLICATIONS FOR REHABILITATIONDespite challenges in feasibility of conducting a randomised controlled trial in female patients with coronary artery disease examining the effects of aerobic interval training versus moderate-intensity continuous exercise on aerobic exercise capacity, there was a significant per protocol treatment effect of 0.95 ml·kg-1·min-1 in favour of aerobic interval training.The cardiac rehabilitation environment provides key facilitators and perceived benefits for exercising and attending cardiac rehabilitation for women, and thus emphasises the need for improving referral and enrolment processes specifically for women into cardiac rehabilitation programs.Aerobic interval training may elicit feelings of fear and physical discomfort, or may be precluded by comorbid conditions, therefore, judicious consideration must be taken in examining the suitability of implementation into clinical practice for each female patient.

Exercise priming with transcranial direct current stimulation: a study protocol for a randomized, parallel-design, sham-controlled trial in mild cognitive impairment and Alzheimer's disease.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive type of brain stimulation that uses electrical currents to modulate neuronal activity. A small number of studies have investigated the effects of tDCS on cognition in patients with Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD), and have demonstrated variable effects. Emerging evidence suggests that tDCS is most effective when applied to active brain circuits. Aerobic exercise is known to increase cortical excitability and improve brain network connectivity. Exercise may therefore be an effective, yet previously unexplored primer for tDCS to improve cognition in MCI and mild AD. METHODS: Participants with MCI or AD will be randomized to receive 10 sessions over 2 weeks of either exercise primed tDCS, exercise primed sham tDCS, or tDCS alone in a blinded, parallel-design trial. Those randomized to an exercise intervention will receive individualized 30-min aerobic exercise prescriptions to achieve a moderate-intensity dosage, equivalent to the ventilatory anaerobic threshold determined by cardiopulmonary assessment, to sufficiently increase cortical excitability. The tDCS protocol consists of 20 min sessions at 2 mA, 5 times per week for 2 weeks applied through 35 cm2 bitemporal electrodes. Our primary aim is to assess the efficacy of exercise primed tDCS for improving global cognition using the Montreal Cognitive Assessment (MoCA). Our secondary aims are to evaluate the efficacy of exercise primed tDCS for improving specific cognitive domains using various cognitive tests (n-back, Word Recall and Word Recognition Tasks from the Alzheimer's Disease Assessment Scale-Cognitive subscale) and neuropsychiatric symptoms (Neuropsychiatric Inventory). We will also explore whether exercise primed tDCS is associated with an increase in markers of neurogenesis, oxidative stress and angiogenesis, and if changes in these markers are correlated with cognitive improvement. DISCUSSION: We describe a novel clinical trial to investigate the effects of exercise priming before tDCS in patients with MCI or mild AD. This proof-of-concept study may identify a previously unexplored, non-invasive, non-pharmacological combination intervention that improves cognitive symptoms in patients. Findings from this study may also identify potential mechanistic actions of tDCS in MCI and mild AD. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03670615 . Registered on September 13, 2018.

Glutathione Peroxidase Activity Is Altered in Vascular Cognitive Impairment-No Dementia and Is a Potential Marker for Verbal Memory Performance.

BACKGROUND: Coronary artery disease (CAD) increases risk for vascular cognitive impairment-no dementia (VCIND), a precursor to dementia, potentially through persistent oxidative stress. OBJECTIVE: This study assessed peripheral glutathione peroxidase activity (GPX), which is protective against oxidative stress, in VCIND versus cognitively normal CAD controls (CN). GPX activity was also evaluated as a biomarker of cognition, particularly verbal memory. METHODS: 120 CAD patients with VCIND (1SD below norms on executive function or verbal memory (VM)) or without (CN) participated in exercise rehabilitation for 24 weeks. Neurocognitive and cardiopulmonary fitness (VO2peak) assessments and plasma were collected at baseline and 24-weeks. RESULTS: GPX was higher in VCIND compared to CN (F1,119 = 3.996, p = 0.048). Higher GPX was associated with poorer baseline VM (ß= -0.182, p = 0.048), and longitudinally with VM decline controlling for sex, body mass index, VO2peak, and education (b[SE] = -0.02[0.01], p = 0.004). Only CN participants showed improved VM performance with increased fitness (b[SE] = 1.30[0.15], p < 0.005). CONCLUSION: GPX was elevated in VCIND consistent with a compensatory response to persistent oxidative stress. Increased GPX predicted poorer cognitive outcomes (verbal memory) in VCIND patients despite improved fitness.

Serum soluble epoxide hydrolase related oxylipins and major depression in patients with type 2 diabetes.

BACKGROUND: People with type 2 diabetes mellitus (T2DM) are at increased risk for depression. Both conditions are associated with disturbances in polyunsaturated fatty acids. Omega-3 and omega-6 fatty acids can be converted into bioactive epoxides by cytochrome P450s (CYP450), which play pro-resolving roles in the inflammatory response; however, soluble epoxide hydrolase (sEH) metabolizes epoxides into diols, which lack pro-resolving functions and can be cytotoxic. Here, we survey serum CYP450- and sEH-derived metabolite concentrations in people with T2DM with and without a major depressive episode. METHODS: Sunnybrook Type 2 Diabetes Study (NCT04455867) participants experiencing a major depressive episode (research version of the Structured Clinical Interview for DSM-5 criteria) were matched 1:1 for gender, glycosylated hemoglobin A1c and body mass index to participants without a current depressive episode. Depression severity was assessed using the Beck Depression Inventory 2nd Edition (BDI-II). From fasting morning blood, unesterified serum oxylipins were quantified by ultra-high-performance liquid chromatography tandem mass spectrometry following solid phase extraction, and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay. RESULTS: Between 20 depressed and 20 non-depressed participants (mean age 58.9 ± 8.5 years, 65% women) with T2DM, several sEH-derived fatty acid diols, but not IL-6, were higher among those with a depressive episode (effect sizes up to d = 0.796 for 17,18-DiHETE, a metabolite of eicosapentaenoic acid [EPA]; t = 2.516, p = 0.016). Among people with a depressive episode, two epoxides were correlated with lower BDI-II scores: 12(13)-EpOME (ρ = -0.541, p = 0.014) and 10(11)-EpDPE (ρ = -0.444, p = 0.049), metabolites of linoleic acid and docosahexaenoic acid (DHA), respectively, while the ratio of 12,13-DiHOME/12(13)-EpOME was correlated with higher BDI-II scores (ρ = 0.513, p = 0.021). CONCLUSIONS: In people with T2DM, major depressive episodes and depressive symptom severity were associated with an oxylipin profile consistent with elimination of pro-resolving lipid mediators by sEH.

Cerebrovascular assessments to help understand brain-related changes associated with aerobic exercise after stroke.

Evidence suggests exercise is "good medicine" after stroke, yet consensus is lacking on the time to initiate, type, exertion level, and duration per session. It remains a challenge to identify outcome measures for stroke-exercise trials that are sufficiently sensitive to intervention parameters. Cerebrovascular assessments, namely cerebral blood flow and intracranial pulsatility, are herein discussed as examples of quantitative brain-specific measures that may be useful to monitor exercise-related brain changes and help to guide stroke rehabilitation interventions. Novelty: Cerebral blood flow and arterial stiffness are potential vascular targets for stroke exercise trials.

Serum osteocalcin is associated with subjective stress in people with depression and type 2 diabetes.

BACKGROUND: Low serum osteocalcin is a risk factor for type 2 diabetes mellitus (T2DM), and osteocalcin release from bone is associated with an acute stress response in mice. Both diabetes and stress are associated with depression. Here, we assess relationships between serum osteocalcin, depression and subjective stress in people with T2DM. METHODS: Participants with T2DM (HbA1c above 6.4 %, impaired fasting glucose or impaired glucose tolerance) were assessed for a major depressive episode using the research version of the Structured Clinical Interview for DSM-5 depression criteria (SCID-5RV). Subjective stress over the past month was assessed using the Perceived Stress Scale (PSS). Serum carboxylated (cOCN) and fully decarboxylated (dcOCN) osteocalcin were assayed from fasting morning blood by commercial enzyme-linked immunosorbent assay. RESULTS: Among 95 participants (mean age 62.4 ± 9.9, 51 % women), 22 % were experiencing a depressive episode (9 men, 12 women). The presence of a depressive episode was not associated with dcOCN or cOCN concentrations; however, higher concentrations of cOCN were associated with higher PSS scores in participants with depression (r = 0.585, p = 0.005). In an analysis of covariance model controlling for age, sex, body mass index, glycemic control (glycosylated hemoglobin), insulin resistance (homeostatic model), depression, and antidepressant use, cOCN was associated with PSS scores (F=10.302, p = 0.002), and this relationship was stronger in those with depression (depression × cOCN interaction F=4.978, p = 0.028). Although associations between dcOCN concentrations and PSS scores did not reach significance, the same trend seen with cOCN concentrations was observed in participants with depression for dcOCN (r=0.365, p=0.10), and for a depression × dcOCN interaction associated with PSS scores in the whole group (F=2.165, p = 0.15). CONCLUSIONS: Osteocalcin is a neuroendocrine marker associated with perceived chronic stress among people with T2DM experiencing a depressive episode.

Endostatin as a Mediator Between Endothelial Function and Cognitive Performance in Those at Risk for Vascular Cognitive Impairment.

BACKGROUND: Patients with coronary artery disease have an increased risk for developing vascular cognitive impairment. Endothelial function is often diminished and has been associated with lower cognitive performance in these patients. The link between endothelial function and cognition in coronary artery disease is not fully understood. Angiogenesis may play a role in mediating the association between endothelial function and cognition since angiogenic processes rely heavily on the endothelium. OBJECTIVE: The aim of this study was to determine if markers of angiogenesis mediate the relationship between endothelial function and cognition in coronary artery disease patients. METHODS: In 50 participants with coronary artery disease, endothelial function was assessed using peripheral arterial tonometry. Vascular endothelial growth factor (pro-angiogenic) and endostatin (anti-angiogenic) were measured in peripheral serum samples. Cognition was assessed using the Montreal Cognitive Assessment. A mediation analysis, using a bias corrected inferential bootstrapping method with 10,000 permutations, was used to determine if vascular endothelial growth factor or endostatin mediated an association between peripheral arterial tonometry measures and cognitive performance on the Montreal Cognitive Assessment. RESULTS: Endostatin, but not vascular endothelial growth factor, mediated a relationship between endothelial function and cognitive performance when controlling for total years of education, body mass index, coronary artery bypass graft, stent, diabetes, and diuretic use. This analysis was also significant when delayed recall was substituted for the overall score on the Montreal Cognitive Assessment. CONCLUSION: These results suggest that endostatin mediates an association between endothelial function and cognitive performance in coronary artery disease.

Quantifying the Occurrence of Shoulder Pain after Cardiac Surgery in a Cardiac Rehabilitation Population.

Purpose: The aim of this study was to identify the occurrence of shoulder pain after cardiac surgery among cardiac rehabilitation participants (CRPs) and its interaction with cardiac rehabilitation (CR). Method: This was a cross-sectional questionnaire-based study of open-heart surgery patients conducted at the midpoint of a 6-month CR programme. We measured the proportion of patients experiencing shoulder pain, onset, location, impact on rehabilitation, and pain and disability using the Shoulder Pain and Disability Index. Results: Of 70 (76% men) CRPs, 47% (33) reported shoulder pain post-surgery, with most (91%; 29 of 32) remaining symptomatic at the time of questionnaire completion, 14.6 (SD 37.9) months post-surgery. Disability and pain scores were 4.2 (SD 2.8) and 5.7 (SD 2.5), respectively (maximum score 10). Of people with shoulder pain participating in resistance training (RT; 19), 8 (42%) reported it was beneficial for shoulder pain; 7 (37%), no effect or unknown; and 4 (21%), some aggravation. Modifications to RT by programme staff were reported by 47% (8) of participants. Of those with shoulder pain, 10 (31%) reported some benefit; 20 (63%), no effect or unknown; and 2 (6%), aggravation from aerobic training. Conclusions: Almost half of the CRPs who had undergone open-heart surgery reported moderately severe and disabling shoulder pain that persisted for at least 14.6 (SD 37.9) months. Almost half the RT participants were prescribed exercise modifications with few negative effects. Shoulder pain is a significant issue after surgery, and appropriate screening is recommended for safe CR participation.

Objectif : établir l'occurrence de douleur à l'épaule après une chirurgie cardiaque chez des patients en réadaptation cardiaque (PRC) et en déterminer l'interaction avec la réadaptation cardiaque (RC). Méthodologie : étude transversale par questionnaire auprès de patients ayant subi une opération à cœur ouvert qui se trouvaient à mi-parcours d'un programme de RC de six mois. Les chercheurs ont mesuré la proportion de patients ressentant des douleurs à l'épaule, l'apparition de la douleur, son siège, ses répercussions sur la réadaptation, de même que la douleur et l'incapacité d'après le score de douleur à l'épaule et d'incapacité. Résultats : chez les 70 PRC (76 % d'hommes), 47 % (33) ont déclaré ressentir une douleur à l'épaule après l'opération, et la plupart (91 %; 29 sur 32) étaient encore symptomatiques au moment de remplir le questionnaire, 14,6 mois (ÉT 37,9) plus tard. Les scores d'incapacité et de douleur s'établissaient à 4,2 (ÉT 2,8) et 5,7 (ÉT 2,5), respectivement (score maximal de 10). Chez les personnes ressentant une douleur à l'épaule qui ont participé à un entraînement en résistance (ER; 19), huit (42 %) ont déclaré ce type d'entraînement bénéfique, sept (37 %) ont trouvé qu'il n'avait aucun effet ou que cet effet était inconnu et seulement quatre (21 %) ont constaté une certaine aggravation. De plus, 47 % des participants (8) ont indiqué que le personnel du programme avait modifié l'ER. Chez ceux qui ressentaient une douleur à l'épaule, dix (31 %) ont déclaré que l'entraînement aérobique procurait certains avantages, 20 (63 %) ont trouvé qu'il n'avait aucun effet ou que cet effet était inconnu et seulement deux (6 %) ont signalé une aggravation. Conclusion : près de la moitié des PRC qui ont subi une opération à cœur ouvert ont déclaré une douleur à l'épaule modérément grave et incapacitante qui a persisté au moins 14,6 mois (ÉT 37,9). Près de la moitié des participants à un ER se sont fait prescrire des modifications aux exercices et en ont ressenti peu d'effets négatifs. La douleur à l'épaule est un problème important après l'opération. Un dépistage approprié est recommandé pour assurer une participation à la RC en toute sécurité.

Effect on Treatment Adherence of Distributing Essential Medicines at No Charge: The CLEAN Meds Randomized Clinical Trial.

Importance: Nonadherence to treatment with medicines is common globally, even for life-saving treatments. Cost is one important barrier to access, and only some jurisdictions provide medicines at no charge to patients. Objective: To determine whether providing essential medicines at no charge to outpatients who reported not being able to afford medicines improves adherence. Design, Setting, and Participants: A multicenter, unblinded, parallel, 2-group, superiority, outcomes assessor-blinded, individually randomized clinical trial conducted at 9 primary care sites in Ontario, Canada, enrolled 786 patients between June 1, 2016, and April 28, 2017, who reported cost-related nonadherence. Follow-up occurred at 12 months. The primary analysis was performed using an intention-to-treat principle. Interventions: Patients were randomly allocated to receive free medicines on a list of essential medicines in addition to otherwise usual care (n = 395) or usual medicine access and usual care (n = 391). Main Outcomes and Measures: The primary outcome was adherence to treatment with all medicines that were appropriately prescribed for 1 year. Secondary outcomes were hemoglobin A1c level, blood pressure, and low-density lipoprotein cholesterol levels 1 year after randomization in participants taking corresponding medicines. Results: Among the 786 participants analyzed (439 women and 347 men; mean [SD] age, 51.7 [14.3] years), 764 completed the trial. Adherence to treatment with all medicines was higher in those randomized to receive free distribution (151 of 395 [38.2%]) compared with usual access (104 of 391 [26.6%]; difference, 11.6%; 95% CI, 4.9%-18.4%). Control of type 1 and 2 diabetes was not significantly improved by free distribution (hemoglobin A1c, -0.38%; 95% CI, -0.76% to 0.00%), systolic blood pressure was reduced (-7.2 mm Hg; 95% CI, -11.7 to -2.8 mm Hg), and low-density lipoprotein cholesterol levels were not affected (-2.3 mg/dL; 95% CI, -14.7 to 10.0 mg/dL). Conclusions and Relevance: The distribution of essential medicines at no charge for 1 year increased adherence to treatment with medicines and improved some, but not other, disease-specific surrogate health outcomes. These findings could help inform changes to medicine access policies such as publicly funding essential medicines. Trial Registration: ClinicalTrials.gov identifier: NCT02744963.

Financial incentives for physical activity in adults: systematic review and meta-analysis.

OBJECTIVE: The use of financial incentives to promote physical activity (PA) has grown in popularity due in part to technological advances that make it easier to track and reward PA. The purpose of this study was to update the evidence on the effects of incentives on PA in adults. DATA SOURCES: Medline, PubMed, Embase, PsychINFO, CCTR, CINAHL and COCH. ELIGIBILITY CRITERIA: Randomised controlled trials (RCT) published between 2012 and May 2018 examining the impact of incentives on PA. DESIGN: A simple count of studies with positive and null effects ('vote counting') was conducted. Random-effects meta-analyses were also undertaken for studies reporting steps per day for intervention and post-intervention periods. RESULTS: 23 studies involving 6074 participants were included (64.42% female, mean age = 41.20 years). 20 out of 22 studies reported positive intervention effects and four out of 18 reported post-intervention (after incentives withdrawn) benefits. Among the 12 of 23 studies included in the meta-analysis, incentives were associated with increased mean daily step counts during the intervention period (pooled mean difference (MD), 607.1; 95% CI: 422.1 to 792.1). Among the nine of 12 studies with post-intervention daily step count data incentives were associated with increased mean daily step counts (pooled MD, 513.8; 95% CI:312.7 to 714.9). CONCLUSION: Demonstrating rising interest in financial incentives, 23 RCTs were identified. Modest incentives ($1.40 US/day) increased PA for interventions of short and long durations and after incentives were removed, though post-intervention 'vote counting' and pooled results did not align. Nonetheless, and contrary to what has been previously reported, these findings suggest a short-term incentive 'dose' may promote sustained PA.

Association Between Sphingolipids and Cardiopulmonary Fitness in Coronary Artery Disease Patients Undertaking Cardiac Rehabilitation.

The long-term benefits conferred by cardiac rehabilitation (CR) in those with coronary artery disease (CAD) are strongly linked with an improvement in cardiopulmonary fitness. This study aimed to determine the association between peripheral sphingolipids and cardiopulmonary fitness in CAD subjects undertaking CR. Patients with CAD (n = 100, mean age = 64 ± 6 years, 85% male, mean years of education = 17 ± 3 years) underwent 6 months of CR with blood collected at baseline, 3 and 6 months. Cardiopulmonary fitness was assessed by measuring peak oxygen uptake (VO2peak) at all time points. High performance liquid chromatography coupled electrospray ionization tandem mass spectrometry was used to quantify plasma sphingolipid concentrations. Cross-sectional and longitudinal associations between sphingolipids and VO2peak were assessed using linear regressions and mixed models, respectively. Higher concentrations of sphingomyelin C18:1 (ß = -0.26, p = .01), ceramides C16:0 (ß = -0.24, p = .02), C18:0 (ß = -0.29, p = .002), C20:0 (ß = -0.24, p = .02) and C24:1 (ß = -0.24, p = .01) and monohexylceramide C18:0 (ß = -0.23, p = .02) were associated with poorer VO2peak at baseline. An improvement in VO2peak was associated with a decrease in sphingomyelin C18:1 (b = -10.09, p = .006), ceramides C16:0 (b = -9.25, p = .0003), C18:0 (b = -5.44, p = .0003) and C24:1 (b = -2.46, p = .006) and monohexylceramide C18:0 (b = -5.37, p = .005). Specific long chain sphingolipids may be useful markers of fitness and response to exercise in CAD.

Randomised controlled trial in women with coronary artery disease investigating the effects of aerobic interval training versus moderate intensity continuous exercise in cardiac rehabilitation: CAT versus MICE study.

BACKGROUND: The primary aim of the present study was to investigate the effects of aerobic interval training (AIT) versus moderate intensity continuous exercise (MICE) on aerobic exercise capacity (V̇O2peak), in women only, with coronary artery disease (CAD) and who were referred to a large, 24-week outpatient cardiac rehabilitation (CR) programme. Secondary objectives included comparing the effects of AIT versus MICE on cognition, cardiovascular risk profile, adherence and quality of life before and after the 24-week CR programme. METHODS: Thirty-one postmenopausal women with CAD (left ventricular ejection fraction >35%; 68.2±9.2 years of age; V̇O2peak: 19.1±3.5 mL kg-1 min-1) were randomised to 24 weeks of usual care MICE (60%-80% of V̇O2peak, five times per week) or AIT (four 4-min intervals at 90%-95% of peak heart rate, three times per week+two times per week usual care MICE). Differences between and within groups were assessed using independent samples t-tests and paired samples t-tests, respectively. Treatment effect analysis of AIT on V̇O2peak and secondary outcomes was determined using analysis of covariance with baseline values as covariates. RESULTS: A randomised controlled trial study design was unfeasible in this female CAD population. Unanticipated challenges in recruitment availability and eligibility, in combination with a 59% and 50% attrition rate in the AIT and MICE group, respectively, rendered this study underpowered to detect differences between groups. The per protocol treatment effect analysis, however, unveiled a 0.95 mL kg-1 min-1 improvement in V̇O2peak in response to AIT over MICE (p<0.001). CONCLUSIONS: Further research is necessary to elucidate the patient profile and circumstances under which the potential for the implementation of AIT may be individualised, and offered in clinical practice. TRIAL REGISTRATION: NCT02966158.

Cerebrovascular Pulsatility During Rest and Exercise Reflects Hemodynamic Impairment in Stroke and Cerebral Small Vessel Disease.

Although aerobic exercise is recommended as a core component of stroke rehabilitation, knowledge of acute cerebrovascular responses in patients is limited. This study tested the hypothesis that older adults with chronic stroke or cerebral small vessel disease (SVD) exhibit a greater increase in pulsatile hemodynamics during exercise compared with young and age-matched healthy adults. Middle cerebral artery blood flow velocity was acquired during 20 min of moderate intensity cycling in 51 participants from four groups (young, old, SVD and stroke). During rest, only the stroke group had a higher pulsatility index (PI) compared with the young group (1.02 ± 0.17 vs 0.83 ± 0.13; p = 0.038). During exercise, however, the SVD group exhibited a larger increase in PI (68 ± 20% relative to rest) than the young (47 ± 19%), old (45 ± 17%) and stroke (40 ± 25%) groups (p < 0.05, for each). The stress of aerobic exercise may reveal arterial dysfunction associated with latent and overt cerebrovascular disease.

Development of Cardiometabolic Health indicators to advance the quality of spinal cord injury rehabilitation: SCI-High Project.

Context: Spinal cord injury or disease (SCI/D) leads to unchanged low-density lipoprotein and cholesterol, very low high-density lipoprotein a form of dyslipidemia and physical inactivity which combine to increase risk of morbidity and mortality from cardiometabolic disease. Herein, we describe the selection of structure, process and outcome indicators for adults in the first 18 months post-SCI/D rehabilitation admission. Methods: A Pan-Canadian Cardiometabolic Health Working Group was formed to develop a construct definition. Cardiometabolic risk factors were summarized in a Driver diagram. Release of the Paralyzed Veterans of America "Identification and Management of Cardiometabolic Risk after Spinal Cord Injury" and the International Scientific Exercise Guidelines: "Evidence-based scientific exercise guidelines for adults with spinal cord injury", informed the group's focus on prevention strategies to advance this Domain of rehabilitation admission. Results: The structure indicator identifies during rehabilitation the presence of appropriate time and resources for physical exercise prescription. Process indicators are lipid profile assessment at rehabilitation admission and documented exercise prescriptions prior to discharge. The outcome indicators track patient's knowledge retention regarding exercise prescription at discharge, current exercise adherence and lipid status 18 months after rehabilitation discharge. Conclusion: Routine national implementation of these indicators at the specified time points will enhance efforts to detect dyslipidemia and assure routine participation in endurance exercise. These indicators align with international initiatives to improve cardiometabolic health through interventions targeting modifiable risk factors specifically endurance exercising and optimal lipid profiles, crucial to augmenting cardiometabolic health after SCI/D.

Validity of a novel screen for cognitive impairment and neuropsychiatric symptoms in cardiac rehabilitation.

BACKGROUND: Currently, there is no composite screening tool that can efficiently and effectively assess prevalent yet under-recognized cognitive and neuropsychiatric comorbidities in patients with cardiovascular disease. We aimed to determine the validity and feasibility of a novel screen assessing cognitive impairment, anxiety, apathy and depression (CAAD screen) in those attending cardiac rehabilitation (CR). METHODS: All patients diagnosed with cardiovascular disease or cardiovascular risk factors entering CR were screened as part of clinical care. A subset of those patients agreed to complete validation assessments (n = 127). Screen results were compared to widely accepted standards for cognition, anxiety, apathy, and depression using a modified receiver operating characteristic (ROC) and area under the curve analysis. RESULTS: The screen was completed by 97% of participants in 10 min or less with an average completion time of approximately 5 min. Screening scores adjusted for age, sex and years of education had acceptable or excellent validity compared to widely accepted standard diagnoses: CAAD-Cog (AUC = 0.80); CAAD-Anx (AUC = 0.81); CAAD-Apathy (AUC = 0.79) and CAAD-Dep (AUC = 0.85). CONCLUSIONS: The CAAD screen may be a valid and feasible tool for detecting cognitive impairment, anxiety, apathy and depression in CR settings.

Plasma Sphingolipids Mediate a Relationship Between Type 2 Diabetes and Memory Outcomes in Patients with Coronary Artery Disease Undertaking Exercise.

BACKGROUND: Exercise prevents recurrent cardiovascular events and it may combat cognitive decline in coronary artery disease (CAD); however, evidence in type 2 diabetes (T2DM) has been mixed. T2DM and memory decline have been associated with differences in the plasma sphingolipidome. OBJECTIVE: Here, we will investigate whether T2DM-related sphingolipids predict less memory improvement over an exercise intervention for CAD. METHODS: Among participants with CAD entering a 6-month exercise intervention, we matched 20 with T2DM to 40 without T2DM for age, sex, and body mass index. We assessed 45 sphingolipid species using high-performance liquid chromatography coupled electrospray ionization tandem mass spectrometry with multiple reaction monitoring. We assessed memory using the California Verbal Learning Test, 2nd Ed, and the revised Brief Visuospatial Learning Test. RESULTS: Partial least squares discriminant analysis identified 8 species that distinguished T2DM from non-T2DM groups with 83% (95% confidence interval [70%, 95%]) accuracy in a receiver operator characteristic curve (validated by internal resampling, 1000 permutations, p = 0.01). At baseline, T2DM-associated sphingolipids (ceramide C22 : 0, monohexylceramide C16 : 1, and lactosylceramide C24 : 0) were associated with poorer memory, attention, and psychomotor processing speed performance. Among 50 completers, an indirect effect of T2DM on less improvement in verbal memory was mediated by monohexylceramide C16 : 1 (0.86 fewer words recalled, 95% bootstrap confidence interval [-2.32, -0.24]), and an indirect effect of T2DM on less visuospatial memory improvement was mediated by ceramide C22 : 0 concentrations (0.42 fewer points, 95% bootstrap confidence interval [-1.17, -0.05]). CONCLUSIONS: Ceramide species associated with T2DM predicted poorer cognitive responses to exercise in patients with CAD.

Age-Related Improvements in Peak Cardiorespiratory Fitness among Coronary Heart Disease Patients Following Cardiac Rehabilitation.

While cardiorespiratory fitness (VO2peak) can be improved with exercise and training, it is unclear whether older age is associated with an attenuated VO2peak improvement among patients with coronary artery disease (CAD) who complete a cardiac rehabilitation (CR) program. A retrospective review of patient demographics and VO2peak data from January 2012 to December 2017 was performed. CAD patients were included if they had successfully completed the supervised 6-month CR program (>75% of exercise prescription) and two VO2peak assessments (respiratory exchange ratio (RER) >1.0). Among all patients, there was an improvement in VO2peak from 21.1 ± 6.3 mL/kg/min to 26.5 ± 7.9 mL/kg/min (+26% ΔVO2peak). Patients in the younger age category (age category 1: 30⁻39 years old) tended to have a greater percent of relative VO2peak improvement when compared to all other age categories (e.g., adults 50 years of age and older). In the regression analysis, VO2peak improvement was associated with younger age (ß = -0.286, p < 0.0001), after adjustment for the baseline VO2peak (ß = -0.456, p < 0.0001), final prescribed exercise speed at CR program completion (ß = 0.254, p < 0.0001), body mass index (ß = -0.172, p < 0.0001), and male sex (ß = 0.153, p < 0.0001). Nonetheless, the study findings indicate that older adults who complete CR may be able to obtain clinically relevant improvements in VO2peak of greater than 20%, and therefore, should be referred for CR.

Association Between Endothelial Function and Cognitive Performance in Patients With Coronary Artery Disease During Cardiac Rehabilitation.

OBJECTIVE: Subtle cognitive deficits indicating early neural risk are common in the clinical presentation of coronary artery disease (CAD). Although deterioration may be mitigated by exercise, cognitive response to exercise is heterogeneous. Vasculopathy including endothelial dysfunction is a hallmark of CAD and may play an important role in impairing neural adaptation to exercise. This study aimed to assess peripheral measurements of endothelial function as predictors of cognitive performance in CAD participants undertaking cardiac rehabilitation (CR). METHODS: CAD patients (N = 64) undergoing CR were recruited for this prospective observational study. Neuropsychological and endothelial function assessments were performed at baseline and after 3 months of CR. Z-scores for overall cognitive performance and specific cognitive domains (verbal and visuospatial memory, processing speed, and executive function) were calculated. Endothelial function was measured by the reactive hyperemia index (RHI) using peripheral arterial tonometry. Cross-sectional and longitudinal associations between RHI and overall cognition were assessed using linear regressions and mixed models, respectively. Domain-specific associations were also explored. RESULTS: Although lower RHI was not associated with overall cognition at baseline (b = 0.26, p = .10), an increased RHI was significantly associated with an improvement in overall cognition (b = 0.55, p = .030) over 3 months. Lower RHI was associated with poorer verbal memory (ß = 0.28, p = .027) at baseline and an increased RHI over 3 months was associated with an improvement in processing speed (b = 0.42, p = .033). CONCLUSIONS: RHI may be a clinically useful predictor of cognitive change and might provide insight into the etiology of cognitive dysfunction in patients with CAD.