Mahwesh Saleem

Major Depressive Disorder Predicts Completion, Adherence, and Outcomes in Cardiac Rehabilitation: A Prospective Cohort Study of 195 Patients With Coronary Artery Disease

OBJECTIVE To compare completion, adherence, and cardiac rehabilitation (CR) outcomes between participants with and without major depressive disorder (MDD) undertaking CR. METHOD In a prospective cohort study of consecutive patients with coronary artery disease (n = 195) entering 1-year outpatient CR between January 2006 and August 2008, rates of noncompletion (comprehensive CR criteria), nonadherence (< 70% attendance at scheduled CR visits), and CR outcomes were compared between patients with and without MDD based on the Structured Clinical Interview for DSM-IV criteria. RESULTS Major depressive disorder was diagnosed in 22.1% of participants. Rates of noncompletion were 44.2% and 28.9%, and rates of nonadherence were 53.0% and 34.9% for those with and without MDD, respectively. Major depressive disorder was associated with increased risks of noncompletion (multivariate hazard ratio [HR], 2.5; 95% confidence interval [CI], 1.3-4.7) and nonadherence (multivariate HR, 2.4; 95% CI, 1.3-4.2). More participants with MDD failed to complete CR for medical reasons than those without MDD (25.6% vs 12.3%, respectively; P = .031) in post hoc comparisons. Participants with MDD achieved poorer cardiopulmonary fitness increases (change in mean ± SD peak oxygen uptake of 3.3 ± 3.2 vs 6.6 ± 5.7 mL/kg/min; P = .021) and poorer body fat outcomes (a mean ± SD increase of 2.1% ± 4.5% vs a decrease of 0.4% ± 3.4%, P = .009) than those without MDD. CONCLUSIONS Major depressive disorder was associated with poorer rates of completion and adherence in CR, and it mitigated improvements in clinical outcomes. Despite depression screening and psychosocial support as structured components of care, MDD remained a significant barrier to effective CR.

Brain derived neurotrophic factor, cardiopulmonary fitness and cognition in patients with coronary artery disease

OBJECTIVE To assess serum brain derived neurotrophic factor (BDNF) concentrations as a correlate of cardiopulmonary fitness and as a predictor of cognitive performance in subjects with coronary artery disease (CAD). METHODS Serum BDNF concentrations were assayed by ELISA and fitness was assessed using a standardized exercise stress test. The Mini Mental Status Examination (MMSE), California Verbal Learning Test 2nd Ed., Stroop, Trail Making Test B and the Digit Symbol-Coding task were administered. The val66met BDNF genotype and serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations were determined as potential confounders. RESULTS In subjects with CAD (n=88; 85.2% male, mean age 62.8±10.5 yr), cardiopulmonary fitness was associated with higher serum BDNF concentrations (β=.305, p=.013). Higher serum BDNF concentrations were associated with higher MMSE scores (F(1,87)=15.406, p<.0005) and better performance on the Digit Symbol-Coding task (F(1,87)=9.620, p=.003). IL-6, TNF-α and the val66met genotype did not influence these results. CONCLUSION Serum BDNF concentrations were associated with cardiopulmonary fitness, psychomotor processing speed and overall cognition in subjects with CAD.

Cardiopulmonary fitness is associated with cognitive performance in patients with coronary artery disease.

OBJECTIVES: To investigate the association between cardiopulmonary fitness and cognitive performance in subjects with coronary artery disease (CAD).

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 (β = 0.471, t = 3.381, df = 44, p = 0.002) and left inferior fronto-occipital fasciculus (β = 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.

Inflammatory Markers in Mild Cognitive Impairment: A Meta-Analysis.

Reports of elevated inflammatory markers in mild cognitive impairment (MCI) suggest that inflammation may be a potential early marker of the neurodegenerative cascade associated with Alzheimers disease (AD). The aim of this study was to quantitatively summarize the data on peripheral blood concentrations of inflammatory factors in patients with MCI compared to controls. Mean (±SD) blood concentrations of inflammatory factors for MCI and control subjects were extracted from original English language peer-reviewed studies for meta-analysis. Twenty-two studies measuring concentrations of cytokines, chemokines, acute phase reactant proteins, immunoglobulins, intercellular adhesion molecules, and fibrinogen were included. No significant differences in inflammatory factors studied were found between subjects with MCI and healthy controls. These findings do not support the involvement of inflammatory markers at the MCI stage of cognitive decline although significant heterogeneity was observed in some comparisons. It remains to be established whether inflammation may predict increased rate of conversion to dementia.

Cardiopulmonary fitness correlates with regional cerebral grey matter perfusion and density in men with coronary artery disease.

Purpose Physical activity is associated with positive effects on the brain but there is a paucity of clinical neuroimaging data in patients with coronary artery disease (CAD), a cardiovascular condition associated with grey matter loss. The purpose of this study was to determine which brain regions are impacted by cardiopulmonary fitness and with the change in fitness after 6 months of exercise-based cardiac rehabilitation. Methods CAD patients underwent magnetic resonance imaging at baseline, and peak volume of oxygen uptake during exercise testing (VO2Peak) was measured at baseline and after 6 months of training. T1-weighted structural images were used to perform grey matter (GM) voxel-based morphometry (VBM). Pseudo-continuous arterial spin labeling (pcASL) was used to produce cerebral blood flow (CBF) images. VBM and CBF data were tested voxel-wise using VO2Peak and age as explanatory variables. Results In 30 men with CAD (mean age 65±7 years), VBM and CBF identified 7 and 5 respective regions positively associated with baseline VO2Peak. These included the pre- and post-central, paracingulate, caudate, hippocampal regions and converging findings in the putamen. VO2Peak increased by 20% at follow-up in 29 patients (t = 9.6, df = 28, p<0.0001). Baseline CBF in the left post-central gyrus and baseline GM density in the right putamen predicted greater change in VO2Peak. Conclusion Perfusion and GM density were associated with fitness at baseline and with greater fitness gains with exercise. This study identifies new neurobiological correlates of fitness and demonstrates the utility of multi-modal MRI to evaluate the effects of exercise in CAD patients.

Cognitive Outcomes following Transcatheter Aortic Valve Implantation: A Systematic Review

Severe aortic stenosis is the most common valvular heart disease in the elderly in the Western world and contributes to a large proportion of all deaths over the age of 70. Severe aortic stenosis is conventionally treated with surgical aortic valve replacement; however, the less invasive transcatheter aortic valve implantation (TAVI) is suggested for those at high surgical risk. While TAVI has been associated with improved survival and favourable outcomes, there is a higher incidence of cerebral microembolisms in TAVI patients. This finding is of concern given mechanistic links with cognitive decline, a symptom highly prevalent in those with cardiovascular disease. This paper reviews the literature assessing the possible link between TAVI and cognitive changes. Studies to date have shown that global cognition improves or remains unchanged over 3 months following TAVI while individual cognitive domains remain preserved over time. However, the association between TAVI and cognition remains unclear due to methodological limitations. Furthermore, while these studies have largely focused on memory, cognitive impairment in this population may be predominantly of vascular origin. Therefore, cognitive assessment focusing on domains important in vascular cognitive impairment, such as executive dysfunction, may be more helpful in elucidating the association between TAVI and cognition in the long term.

Verbal memory performance and completion of cardiac rehabilitation in patients with coronary artery disease.

Objective: To assess cognitive performance as a predictor of noncompletion of cardiac rehabilitation (CR) using a standardized verbal memory test. Methods: This was a prospective cohort study of consecutive patients with coronary artery disease (n = 131) entering 1-year outpatient CR between April 2007 and May 2009. Verbal memory performance was assessed using the California Verbal Learning Test, Second Edition. Attendance at weekly CR sessions was recorded, and completion or noncompletion was determined according to comprehensive CR criteria. Depression was diagnosed according to DSM-IV criteria as a possible confounder. Results: Verbal memory performance at entry into CR differed significantly (F(1,130) = 7.80, p =.006) between noncompleters and completers (mean [SD] cumulative California Verbal Learning Test, Second Edition, score, −1.15 [2.59] versus 0.47 [3.12]) in analysis of covariance controlling for pertinent clinical confounders. Better verbal memory performance predicted a reduced risk of noncompletion (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.77-0.96, p =.009) in time-to-event analysis adjusted for depression (HR = 2.62, 95% CI = 1.33-5.17, p =.006) and smoking history (HR = 2.03, 95% CI = 0.98-4.22, p =.06). A post hoc analysis suggested that better verbal memory performance predicted a reduced risk of noncompletion for medical reasons (HR = 0.83, 95% CI = 0.70-0.99, p =.03). Conclusions: Poorer verbal memory performance was associated with an increased risk of noncompletion of CR among participants with coronary artery disease. Further studies exploring practical methods for screening and targeted support might improve rehabilitation outcomes.CR = cardiac rehabilitation; CAD = coronary artery disease; MMSE = Mini-Mental Status Examination; CABG = coronary artery bypass graft; CES-D = Center for Epidemiologic Studies Depression scale; CVLT-II = California Verbal Learning Test, Second Edition; HR = hazard ratio

Higher Cortisol Predicts Less Improvement in Verbal Memory Performance after Cardiac Rehabilitation in Patients with Coronary Artery Disease

Objective. While physical activity can improve verbal memory performance in subjects with coronary artery disease (CAD), there is large variability in response. Elevated cortisol production has been suggested to negatively affect verbal memory performance, yet cortisol concentrations have not been assessed as a predictor of response to exercise intervention in those with CAD. Methods. CAD patients participating in a one-year cardiac rehabilitation program were recruited. Memory was assessed with the California Verbal Learning Test second edition at baseline and one year. Cortisol was measured from a 20 mg, 3.0 cm hair sample collected at baseline. Results. In patients with CAD (n = 56, mean ± SD age = 66 ± 11, 86% male), higher cortisol (hair cortisol concentrations ≥ 153.2 ng/g) significantly predicted less memory improvement (F1,50 = 5.50, P = 0.02) when controlling for age (F1,50 = 0.17, P = 0.68), gender (F1,50 = 2.51, P = 0.12), maximal oxygen uptake (F1,50 = 1.88, P = 0.18), and body mass index (F1,50 = 3.25, P = 0.08). Conclusion. Prolonged hypothalamic pituitary adrenal axis activation may interfere with exercise-related improvements in memory in CAD.

Regional Cerebral Arterial Transit Time Hemodynamics Correlate with Vascular Risk Factors and Cognitive Function in Men with Coronary Artery Disease

BACKGROUND AND PURPOSE: Arterial transit time is the time needed for blood to travel from large arteries to capillaries, as estimated from arterial spin-labeling MR imaging. The purpose of this study was to determine whether vascular risk factors and cognitive performance are related to regional differences in cerebral arterial transit time in patients with coronary artery disease who are at risk for cognitive decline. MATERIALS AND METHODS: Arterial transit time was estimated from multiple postlabel delay pseudocontinuous arterial spin-labeling images obtained from 29 men with coronary artery disease. Tests of memory, attention, processing speed, and executive function were administered. Principal component analysis was used to create separate models of cognition and vascular risk, which were related to brain regions through voxelwise analyses of arterial transit time maps. RESULTS: Principal component analysis identified 2 components of vascular risk: 1) “pressor” (age, systolic blood pressure, and pulse pressure) and 2) “obesity” (body fat percentage and body mass index). Obesity was inversely related to arterial transit time in the posterior cingulate, precuneus, lateral occipital cortices, middle temporal gyrus, and frontal pole (P corrected < .05), whereas pressor was not significant. Cognitive scores were factored into a single component. Poor performance was inversely related to precuneus arterial transit time (P corrected < .05). The average arterial transit time in regions identified by obesity was associated with poorer cognitive function (r2 = 0.21, t = −2.65, P = .01). CONCLUSIONS: Altered cerebral hemodynamics, notably in nodal structures of the default mode network, may be one way that vascular risk factors impact cognition in patients with coronary artery disease.