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.

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.

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 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.

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.

Subcortical hyperintensities in the cholinergic system are associated with improvements in executive function in older adults with coronary artery disease undergoing cardiac rehabilitation.

OBJECTIVE: Coronary artery disease (CAD) is frequently accompanied by white matter hyperintensities and executive dysfunction. Because acetylcholine is important in executive function, these symptoms may be exacerbated by subcortical hyperintensities (SH) located in cholinergic (CH) tracts. This study investigated the effects of SH on cognitive changes in CAD patients undergoing a 48-week cardiac rehabilitation program. METHODS: Fifty patients (age 66.5 ± 7.1 years, 84% male) underwent the National Institute of Neurological Disorders and Stroke - Canadian Stroke Network neurocognitive battery at baseline and 48 weeks. Patients underwent a 48-week cardiac program and completed neuroimaging at baseline. Subcortical hyperintensities in CH tracts were measured using Lesion Explorer. Repeated measures general linear models were used to examine interactions between SH and longitudinal cognitive outcomes, controlling for age, education, and max VO2 change as a measure of fitness. RESULTS: In patients with SH in CH tracts, there was a significant interaction with the Trail Making Test (TMT) part A and part B over time. Patients without SH improved on average 16.6 and 15.0% on the TMT-A and TMT-B, respectively. Patients with SH on average showed no improvements in either TMT-A or TMT-B over time. There were no significant differences in other cognitive measures. CONCLUSION: These results suggest that CAD patients with SH in CH tracts improve less than those without SH in CH tracts, over 48 weeks of cardiac rehabilitation. Thus, SH in CH tracts may contribute to longitudinal cognitive decline following a cardiac event and may represent a vascular risk factor of cognitive decline. © 2017 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd.

The energy expenditure benefits of reallocating sedentary time with physical activity: a systematic review and meta-analysis.

Background: We compared direct and daily cumulative energy expenditure (EE) differences associated with reallocating sedentary time to physical activity in adults for meaningful EE changes. Methods: Peer-reviewed studies in PubMed, Medline, EMBASE, CINAHL, PsycINFO, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews were searched from inception to March 2017. Randomized and non-randomized interventions with sedentary time and EE outcomes in adults were included. Study quality was assessed by the National Heart Lung and Blood Institute tool, and summarized using random-effects meta-analysis and meta-regression. Results: In total, 26 studies were reviewed, and 24 studies examined by meta-analysis. Reallocating 6-9 h of sedentary time to light-intensity physical activity (LIPA) (standardized mean difference [SMD], 2.501 [CI: 1.204-5.363]) had lower cumulative EE than 6-9 h of combined LIPA and moderate-vigorous intensity physical activity (LIPA and moderate-vigorous physical activity [MVPA]) (SMD, 5.218 [CI: 3.822-6.613]). Reallocating 1 h of MVPA resulted in greater cumulative EE than 3-5 h of LIPA and MVPA, but <6-9 h of LIPA and MVPA. Conclusions: Comparable EE can be achieved by different strategies, and promoting MVPA might be effective for those individuals where a combination of MVPA and LIPA is challenging.

Centre- versus home-based exercise among people with mci and mild dementia: study protocol for a randomized parallel-group trial.

BACKGROUND: Worldwide, almost 50million people lived with dementia in 2016. A cure or disease modifying pharmaceutical treatment for dementia remains elusive so alternative therapies are of critical importance. Mounting evidence supports exercise in the prevention and therapy of dementia. However, the cognitive, physical, and psychological challenges common to dementia along with a poor understanding and accommodation of dementia in the community are major barriers to exercise. Consequently, effective delivery options need to be identified. The primary objective of this study is to compare the effectiveness of center-based (CB) exercise versus home-based (HB) exercise for achievement of physical activity guidelines among people with MCI or mild dementia. METHODS: This is a randomized parallel-group trial comparing the effects of CB and HB exercise adherence among community-dwelling adults ≥50 years with a clinical diagnosis of MCI or mild dementia. Participants will be randomized to either CB or HB exercise. The CB group will meet weekly for small group exercise and will be prescribed additional exercise to be completed independently. Participants in the HB group will be given a physical activity prescription to be completed independently in the community. Participants in HB will also be contacted by phone monthly to adjust exercise prescriptions. The primary outcome will be achievement of exercise guidelines (150 min/wk. of moderate activity) assessed using an activity monitor. Secondary objectives will evaluate cost-effectiveness and the influence of individual and environmental factors on the primary outcome. Tertiary outcomes include physical function, cognition, mood, and quality of life. DISCUSSION: There is scant research to indicate the most effective way to deliver exercise to people with MCI and mild dementia, which is needed specifically because these groups face significant barriers to exercise. To capitalize on the benefits of exercise, feasible exercise delivery options need to be identified. The results of this study will directly complement ongoing clinical trials and will be essential to implementing exercise recommendations specific to the prevention and therapy of dementia in a feasible and cost-effective manner when they emerge. TRIAL REGISTRATION: Clinicatrials.gov ; Identifier: NCT02774720 (version updated December 12, 2016).

Oxidative stress predicts depressive symptom changes with omega-3 fatty acid treatment in coronary artery disease patients.

BACKGROUND: Antidepressant efficacy of omega-3 polyunsaturated fatty acid (n-3 PUFA) treatment in coronary artery disease (CAD) patients remains unpredictable. N-3 PUFA can mitigate oxidative stress, which is common in CAD and may contribute to depressive symptoms. This study investigated whether greater pre-treatment oxidative stress, measured by the ratios of late-stage lipid peroxidation markers (malondialdehyde [MDA], 4-hydroxy-2-nonenal [4-HNE], and 8-isoprostane [8-ISO]) to an early-stage marker (lipid hydroperoxides [LPH]), predicted n-3 PUFA antidepressant benefits in CAD. METHODS: This was a secondary analysis of CAROTID (CAD Randomized Omega-3 Trial in Depression, NCT00981383). Patient demographics and medical characteristics were collected. Depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale (HAM-D). Patients were then randomized to receive either 1.9g/day n-3 PUFA or placebo for 12weeks, after which HAM-D scores were reassessed. Baseline LPH, 4-HNE, 8-ISO, MDA and n-3 PUFA concentrations were analysed from fasting blood. RESULTS: Seventy-nine patients (age=61.1±8.5, 76% male, HAM-D=7.5±6.1) were included (n=45 placebo, n=34 n-3 PUFA). In the n-3 PUFA group, higher baseline ratios of MDA/LPH (primary analysis: F1,33=6.20, beta=-0.35, p=0.018), 4-HNE/LPH (exploratory analysis: F1,33=5.35, beta=-0.32, p=0.027), and 8-ISO/LPH (exploratory analysis: F1,33=6.10, beta=-0.33, p=0.019), indicating higher oxidative stress, were associated with greater depressive symptom improvement. In each model, higher baseline EPA+DHA concentrations independently predicted depressive symptom improvement with n-3 PUFA (MDA/LPH: F1,33=11.05, p=0.002; 4-HNE/LPH: F1,33=11.36, p=0.002; 8-ISO/LPH: F1,33=13.15, p=0.001). No associations were observed in the placebo group. CONCLUSIONS: n-3 PUFA may be more likely to improve depressive symptoms in CAD patients with pre-treatment evidence of oxidative stress.

Omega-3/omega-6 fatty acid ratios in different phospholipid classes and depressive symptoms in coronary artery disease patients.

Depressive symptoms are highly incident among coronary artery disease (CAD) patients and increase mortality. Reduced ratios of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (omega-3 fatty acids) to arachidonic acid (AA, omega-6 fatty acid) concentrations have been linked with depressive symptoms in CAD. It remains unclear whether depressive symptoms are differentially associated with that ratio in different phospholipid classes, and this may have mechanistic implications. This study investigated associations between depressive symptoms in CAD patients and the EPA+DHA to AA ratio in the major phospholipid classes. This was a cross-sectional study of stable CAD patients. Sociodemographic, medical, medication, and cardiopulmonary fitness data were collected from each patient. Each patient was assessed for depressive symptoms using the 17-item Hamilton Depression Rating Scale (HAM-D). The percentage of EPA, DHA, and AA in each erythrocyte phospholipid class was determined using gas chromatography from fasting blood. Relationships between EPA+DHA to AA ratios and depressive symptoms were assessed using linear regression and were corrected for multiple comparisons. Seventy-six CAD patients were included (age=61.9 ± 8.5, 74% male, HAM-D=7.2 ± 5.9). In a backward elimination linear regression model, lower EPA+DHA to AA in erythrocyte phosphatidylinositol (B=-12.71, ß=-0.33, p<.01) and sphingomyelin (B=-2.52, ß=-0.37, p<.01) was associated with greater depressive symptom severity, independently of other known predictors. Other phospholipid classes were not associated with depressive symptoms. In conclusion, the relationship between EPA+DHA to AA ratios and depressive symptoms in CAD may not be consistent across phospholipid classes. Continued investigation of these potentially differential relationships may clarify underlying disease mechanisms.

Omega-3 Fatty Acids, Depressive Symptoms, and Cognitive Performance in Patients With Coronary Artery Disease: Analyses From a Randomized, Double-Blind, Placebo-Controlled Trial.

This trial investigated the efficacy of omega-3 polyunsaturated fatty acid (n-3 PUFA) treatment for improving depressive symptoms and cognitive performance in patients with coronary artery disease (CAD) participating in cardiac rehabilitation. Patients with CAD aged 45 to 80 years were randomized to receive either 1.9-g/d n-3 PUFA treatment or placebo for 12 weeks. Depressive symptoms were measured using the Hamilton Depression Rating Scale (HAM-D, primary outcome) and the Beck Depression Inventory II (BDI-II). Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria were used to identify a depressive episode at baseline. Cognitive performance was measured using a standardized battery for vascular cognitive impairment. In 92 patients (age, 61.7 ± 8.7 y; 76% male, 40% depressed; HAM-D, 6.9 ± 5.9; BDI-II, 12.3 ± 10.9; n = 45 n-3 PUFA, n = 47 placebo), depression decreased (HAM-D, F3,91 = 2.71 and P = 0.049; BDI-II, F3,91 = 6.24 and P < 0.01), and cognitive performance improved (attention/processing speed, F1,91 = 5.57, P = 0.02; executive function, F1,91 = 14.64, P < 0.01; visuospatial memory, F1,91 = 4.01, P = 0.04) over cardiac rehabilitation. Omega-3 PUFA treatment increased plasma eicosapentaenoic acid (F1,29 = 33.29, P < 0.01) and docosahexaenoic acid (F1,29 = 15.29, P < 0.01) concentrations but did not reduce HAM-D (F3,91 = 1.59, P = 0.20) or BDI-II (F3,91 = 0.46, P = 0.50) scores compared with placebo. Treatment did not improve cognitive performance; however, n-3 PUFAs significantly increased verbal memory compared with placebo in a subgroup of nondepressed patients (F1,54 = 4.16, P = 0.04). This trial suggests that n-3 PUFAs do not improve depressive and associated cognitive symptoms in those with CAD. The possible benefits of n-3 PUFAs for verbal memory may warrant investigation in well-powered studies.

Sedentary time and its association with risk for disease incidence, mortality, and hospitalization in adults: a systematic review and meta-analysis.

BACKGROUND: The magnitude, consistency, and manner of association between sedentary time and outcomes independent of physical activity remain unclear. PURPOSE: To quantify the association between sedentary time and hospitalizations, all-cause mortality, cardiovascular disease, diabetes, and cancer in adults independent of physical activity. DATA SOURCES: English-language studies in MEDLINE, PubMed, EMBASE, CINAHL, Cochrane Library, Web of Knowledge, and Google Scholar databases were searched through August 2014 with hand-searching of in-text citations and no publication date limitations. STUDY SELECTION: Studies assessing sedentary behavior in adults, adjusted for physical activity and correlated to at least 1 outcome. DATA EXTRACTION: Two independent reviewers performed data abstraction and quality assessment, and a third reviewer resolved inconsistencies. DATA SYNTHESIS: Forty-seven articles met our eligibility criteria. Meta-analyses were performed on outcomes for cardiovascular disease and diabetes (14 studies), cancer (14 studies), and all-cause mortality (13 studies). Prospective cohort designs were used in all but 3 studies; sedentary times were quantified using self-report in all but 1 study. Significant hazard ratio (HR) associations were found with all-cause mortality (HR, 1.240 [95% CI, 1.090 to 1.410]), cardiovascular disease mortality (HR, 1.179 [CI, 1.106 to 1.257]), cardiovascular disease incidence (HR, 1.143 [CI, 1.002 to 1.729]), cancer mortality (HR, 1.173 [CI, 1.108 to 1.242]), cancer incidence (HR, 1.130 [CI, 1.053 to 1.213]), and type 2 diabetes incidence (HR, 1.910 [CI, 1.642 to 2.222]). Hazard ratios associated with sedentary time and outcomes were generally more pronounced at lower levels of physical activity than at higher levels. LIMITATION: There was marked heterogeneity in research designs and the assessment of sedentary time and physical activity. CONCLUSION: Prolonged sedentary time was independently associated with deleterious health outcomes regardless of physical activity. PRIMARY FUNDING SOURCE: None.

Feasibility and Effects of Cardiac Rehabilitation for Individuals after Transient Ischemic Attack.

BACKGROUND AND OBJECTIVE: Cardiac rehabilitation programs (CRPs) are common for cardiac patients; however, most individuals post transient ischemic attack (TIA) receive no rehabilitation despite similar pathologies. The objective of this study is to determine effects of cardiac rehabilitation (CR) on cardiovascular fitness (peak oxygen uptake [VO2peak]) and 6-minute walk distance (6MWD) post TIA. Secondary outcomes included other clinical and process indicators. METHODS: Eighty-five people post TIA (mean age 67.5 ± 10.7, 47% female) were referred to CR (2006-2014). The retro-TIA cohort included 65 consecutively enrolled individuals who were evaluated retrospectively. To collect additional measures, the pro-TIA cohort included 20 participants who were followed prospectively with a 3-month nonintervention period followed by 6-months of CR with 6MWD, cognition, depression score, and anthropometrics measured at each time point. Baseline, 6-month cardiopulmonary exercise test results, depression score, and anthropometrics were examined separately for both cohorts. RESULTS: Among all participants, 62% completed CR with 72.8 ± 17.7% attendance to prescheduled classes. CR resulted in improvements in VO2peak for both cohorts (both, P < .02). In the retro-TIA cohort, there were improvements in resting heart rate and body mass index, with reductions in the proportion of people with obesity and abdominal obesity (all, P < .04). In the pro-TIA cohort, compared to the stable baseline period there was a significant improvement with the CR intervention in the depression score (Δ1.1 ± 4.3 and Δ-3.3 ± 3.9, respectively; P = .04) but not in 6MWD (Δ4.8 ± 42 m and Δ61.0 ± 73.5 m, respectively; P = .06). For all participants, regression analysis revealed a higher depression score (ß = 1.10, P = .02), male sex (ß = 4.932, P = .02), and less social support (ß = 4.085, P = .04) as predictors of dropout. CONCLUSIONS: A CRP is feasible and effective for improving cardiovascular health. Strategies to promote adherence in men, in those with depressive symptoms, and in those with less social support require investigation.

Factors Affecting Attendance at an Adapted Cardiac Rehabilitation Exercise Program for Individuals with Mobility Deficits Poststroke.

OBJECTIVE: The aim of this study was to determine the factors affecting attendance at an adapted cardiac rehabilitation program for individuals poststroke. METHODS: A convenience sample of ambulatory patients with hemiparetic gait rated 20 potential barriers to attendance on a 5-point Likert scale upon completion of a 6-month program of 24 prescheduled weekly sessions. Sociodemographic characteristics, depressive symptoms, cardiovascular fitness, and comorbidities were collected by questionnaire or medical chart. RESULTS: Sixty-one patients attended 77.3 ± 12% of the classes. The longer the elapsed time from stroke, the lower the attendance rate (r = -.34, P = .02). The 4 greatest barriers influencing attendance were severe weather, transportation problems, health problems, and traveling distance. Health problems included hospital readmissions (n = 6), influenza/colds (n = 6), diabetes and cardiac complications (n = 4), and musculoskeletal issues (n = 2). Of the top 4 barriers, people with lower compared to higher income had greater transportation issues (P = .004). Greater motor deficits of the stroke-affected leg were associated with greater barriers related to health issues (r = .7, P = .001). The only sociodemographic factor associated with a higher total mean barrier score was non-English as the primary language spoken at home (P = .002); this factor was specifically related to the barriers of cost (P = .007), family responsibilities (P = .018), and lack of social support (P = .001). No other associations were observed. CONCLUSION: Barriers to attendance were predominantly related to logistic/transportation and health issues. People who were more disadvantaged socioeconomically (language, finances), and physically (stroke-related deficits) were more affected by these barriers. Strategies to reduce these barriers, including timely referral to exercise programs, need to be investigated.

White Matter Microstructural Integrity Is Associated with Executive Function and Processing Speed in Older Adults with Coronary Artery Disease.

OBJECTIVE: Coronary artery disease (CAD) is associated with an increased risk of cognitive decline. Although cerebral white matter (WM) damage predicts cognitive function in CAD, conventional neuroimaging measures only partially explain the effect of CAD on cognition. The purpose of this study was to determine if WM microstructural integrity and CAD using diffusion tensor imaging (DTI) correlates with cognitive function in older adults with CAD. METHODS: Forty-nine CAD patients (66 ± 7 years old, 86% male) underwent neurocognitive assessments using the cognitive battery recommended by the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network for the study of vascular cognitive impairment. Composite scores for each cognitive domain were calculated. Microstructural integrity in normal-appearing WM was quantified as fractional anisotropy (FA) using DTI in nine bilateral and two interhemispheric WM tracts from the Johns Hopkins University WM Tractography Atlas. Linear regression models examined associations between FA and cognitive performance, controlling for age, sex, and education, with correction for multiple comparisons using a false discovery rate of 5%. RESULTS: Executive function was most significantly associated with FA in the left parahippocampal cingulum (ß = 0.471, t = 3.381, df = 44, p = 0.002) and left inferior fronto-occipital fasciculus (ß = 0.430, t = 2.984, df = 44, p = 0.005). FA was not associated with memory in any of the WM tracts examined. CONCLUSION: These results suggest that WM microstructural integrity may be an important neural correlate of executive function even in cognitively intact CAD patients. This study suggests WM damage may be relevant to subtle cognitive decline in a population that may have early neural risk for dementia.

Platelet-activating factors are associated with cognitive deficits in depressed coronary artery disease patients: a hypothesis-generating study.

BACKGROUND: Patients with coronary artery disease (CAD) are at risk of accelerated cognitive decline, particularly those with major depression. Mechanisms for cognitive deficits associated with CAD, and the effects of depression, remain poorly understood. However, CAD is associated with inflammatory processes that have been linked to neurodegeneration, may contribute to cognitive decline, and are elevated in depression. Platelet-activating factors (PAFs) are emerging as key lipid mediators that may be central to those processes and highly relevant to cognitive decline in CAD. METHODS: This cross-sectional study investigated relationships between various PAFs and cognitive performance in 24 patients with CAD (age, 60.3 ± 9.4; 70.8% male). Analyses were repeated in a subgroup of 15 patients with CAD with major depression (DSM-IV). Cognitive performance was assessed using a standardized battery and summary z scores were calculated based on age, sex, and education norms. Global cognitive performance was the average of domain-specific z scores. Plasma PAF analyses were performed using electrospray ionization mass spectrometry (precursor ion scan). RESULTS: A greater abundance of PAF PC(O-18:0/2:0) was associated with poorer global cognitive performance in patients with CAD (r=-0.45, P=0.03). In the major depressed subgroup, PAF PC(O-18:0/2:0) (r=-0.59, P=0.02) as well as PC(O-16:0/2:0) (r=-0.52, P=0.04), and lyso-PAF PC(O-16:0/0:0) (r=-0.53, P=0.04) were associated with poorer global cognitive performance. A greater abundance of PAF PC(O-19:5/2:0) was associated with better global cognitive performance (r=0.55, P=0.03), suggesting a possible compensatory species. CONCLUSIONS: This study suggests that certain PAFs might be associated with global cognitive performance in patients with CAD, with stronger relationships observed in those with major depression. Confirmation of these preliminary findings is warranted.

Assessing cognitive effects of anticholinergic medications in patients with coronary artery disease.

BACKGROUND: Cognitive function is a significant determinant of overall quality of life in patients with coronary artery disease. Medications prescribed to control vascular risk factors often have anticholinergic effects, which can cause central side effects and affect cognitive function. OBJECTIVE: This cross-sectional study aimed to identify cognitive deficits associated with the use of anticholinergic medications in patients with coronary artery disease. METHODS: Demographics, medications, and vascular risk factors were assessed for each patient by interview and chart review. Anticholinergic burden was estimated using the anticholinergic cognitive burden scale. Cognition was assessed objectively using a battery of neuropsychologic tests, including the California Verbal Learning Test second edition, Revised Brief Visuospatial Memory Test, Stroop test, Trail-Making Test Parts A and B, Digit-Symbol Coding, FAS test, and animal naming. RESULTS: Patients with coronary artery disease (mean ± standard deviation age 64.2 ± 9.1, 15.3% female) presented with 2.6 ± 1.4 vascular risk factors and were using 5.1 ± 1.8 medications. Scores on the anticholinergic cognitive burden scale were associated with poorer performance on the Trail-Making Test Part A (ß = 0.280, p = 0.002), Trail-Making Test Part B (ß = 0.256, p = 0.004), and animal naming (ß = -0.212; p = 0.015) tasks in models controlling for age, gender, years of education, number of vascular risk factors and total medications. Beta-blockers frequently prescribed in this population (i.e., metoprolol and atenolol) accounted for a large proportion of the total anticholinergic cognitive burden score, and their use was independently associated with poorer cognitive performance in a post hoc model including the anticholinergic estimate. CONCLUSIONS: Anticholinergic exposure was associated with poorer performance on tests of attention, speed, and executive function in patients with coronary artery disease.

Outcomes in people after stroke attending an adapted cardiac rehabilitation exercise program: does time from stroke make a difference?

BACKGROUND: Individuals referred to cardiac rehabilitation programs (CRPs) after stroke have demonstrated postprogram improvements in cardiovascular fitness (VO2peak). However, the effect of CRPs on other physiological/quality-of-life outcomes and effect of time from stroke on these results has not been investigated. The objectives of the present study are (1) to evaluate the effects of a CRP in participants with motor impairment after stroke and (2) to explore the effects of elapsed time from stroke on physiological/quality-of-life outcomes. METHODS: The CRP included 24 weeks of resistance and aerobic training. Primary outcomes in 120 participants, 25.4±42.3 (mean±standard deviation) months after stroke, included 6-minute walk distance (6MWD), VO2peak, timed repeated sit-to-stand performance, and affected-side isometric knee extensor strength (IKES). Secondary measures included gait characteristics (cadence, step lengths, and symmetry), walking speed, balance (Berg Balance Scale), affected-side range of motion (ROM), elbow flexor and grip strength, anaerobic threshold, and perceptions of participation/social reintegration. RESULTS: After adjusting for multiple comparisons, participants demonstrated significant improvements (all P<.001) in 6MWD (283.2±126.6 to 320.7±141.8 m), sit-to-stand performance (16.3±9.5 to 13.3±7.1 seconds), affected-side IKES (25.9±10.1 to 30.2±11 kg as a percentage of body mass), and VO2peak (15.2±4.5 to 17.2±4.9 mL·kg·min(-1)). Participants also demonstrated post-CRP improvements in secondary outcomes: anaerobic threshold, balance, affected-side hip/shoulder ROM, grip and isometric elbow flexor strength, participation, walking speed, cadence (all P<.001), and bilateral step lengths (P<.04). In a linear regression model, there was a negative association between the change in 6MWD and time from stroke (ß=-42.1; P=.002) independent of baseline factors. CONCLUSIONS: A CRP yields improvements over multiple domains of recovery; however, those who start earlier demonstrate greater improvement in functional ambulation independent of baseline factors. These data support the use of adapted CRPs as a standard of care practice after conventional stroke rehabilitation.

Cytochrome P450-soluble epoxide hydrolase oxylipins, depression and cognition in type 2 diabetes.

AIMS: This study examined serum cytochrome P450-soluble epoxide hydrolase (CYP450-sEH) oxylipins and depressive symptoms together in relation to cognitive performance in individuals with type 2 diabetes mellitus (T2DM). METHODS: Clinically cognitively normal T2DM individuals were recruited (NCT04455867). Depressive symptom severity was assessed using the Beck Depression Inventory-II (BDI-II; total scores ≤13 indicated minimal depressive symptoms and ≥ 14 indicated significant depressive symptoms). Executive function and verbal memory were assessed. Fasting serum oxylipins were quantified by ultra-high-performance liquid chromatography tandem mass-spectrometry. RESULTS: The study included 85 participants with minimal depressive symptoms and 27 with significant symptoms (mean age: 63.3 ± 9.8 years, 49 % women). In all participants, higher concentrations of linoleic acid derived sEH (12,13-dihydroxyoctadecamonoenoic acid; DiHOME) and CYP450 (12(13)-epoxyoctadecamonoenoic acid; EpOME) metabolites were associated with poorer executive function (F1,101 = 6.094, p = 0.015 and F1,101 = 5.598, p = 0.020, respectively). Concentrations of multiple sEH substrates interacted with depressive symptoms to predict 1) poorer executive function, including 9(10)-EpOME (F1,100 = 12.137, p < 0.001), 5(6)-epoxyeicosatrienoic acid (5(6)-EpETrE; F1,100 = 6.481, p = 0.012) and 11(12)-EpETrE (F1,100 = 4.409, p = 0.038), and 2) verbal memory, including 9(10)-EpOME (F1,100 = 4.286, p = 0.041), 5(6)-EpETrE (F1,100 = 6.845, p = 0.010), 11(12)-EpETrE (F1,100 = 3.981, p = 0.049) and 14(15)-EpETrE (F1,100 = 5.019, p = 0.027). CONCLUSIONS: Associations of CYP450-sEH metabolites and depressive symptoms with cognition highlight the biomarker and therapeutic potential of the CYP450-sEH pathway in T2DM.