Taylor, Jenna L

Patients with cardiovascular diseases (CVDs) (including heart failure) are at increased risk of cognitive impairment and dementia. Vascular risk factors contribute to cognitive decline through cerebral small vessel diseases, pathological brain changes, and hypoperfusion. Habitual exercise and increased cardiorespiratory fitness are associated with higher cognitive function, greater cerebral blood flow, and attenuation of the decline in gray matter volume and white matter integrity. Furthermore, moderate-vigorous exercise training has been shown to improve cognitive function in healthy middle-aged and older adults. Cardiac rehabilitation (CR) is a class 1A recommendation for patients with CVD, which involves exercise training and intensive risk factor modification. This article reviews the current evidence for the effect of exercise-based CR on cognitive function, cerebrovascular function, and brain structure in patients with CVDs. Overall, exercise-based CR appears to improve global cognitive function and attention-psychomotor functions but not language processes. Furthermore, the effect of exercise-based CR on executive function and memory is less clear and there is limited research into the effect of exercise-based CR on cerebrovascular function and brain structure.

Adults with cardiovascular disease and heart failure are at higher risk of cognitive decline. Cerebral hypoperfusion appears to be a significant contributor, which can result from vascular dysfunction and impairment of cerebral blood flow regulation. In contrast, higher cardiorespiratory fitness shows protection against brain atrophy, reductions in cerebral blood flow, and cognitive decline. Given that high intensity interval training (HIIT) has been shown to be a potent stimulus for improving cardiorespiratory fitness and peripheral vascular function, its utility for improving cognitive aging is an important area of research. This article will review the physiology related to cerebral blood flow regulation and cognitive decline in adults with cardiovascular disease and heart failure, and how HIIT may provide a more optimal stimulus for improving cognitive aging in this population.

Objective Hypercapnia, an elevated concentration of carbon dioxide (CO2) in the blood, is known to promote acute increases in cerebral blood flow (CBF). This pilot study aimed to investigate whether a novel training method involving repeated bouts of hypercapnia, would influence cerebrovascular reactivity response in healthy adults. Hypothesis Repeated bouts of hypercapnia (as interval training) may promote beneficial adaptation to increase cerebrovascular reactivity. Methods Adults over 40yrs old without known disease or cardiovascular risk factors, were recruited for a non‐randomized cross‐over design pilot study. Subjects completed a 2‐week control period followed by a 2‐week intervention. The intervention involved a progressive hypercapnia training program of six sessions, whereby subjects completed 4‐6 intervals of rebreathing oxygen until a target end‐tidal CO2 (up to 25mmHg above resting) was reached, separated by recovery intervals breathing room air. Cerebrovascular reactivity was measured during study testing visits at baseline, 2‐weeks (between control and intervention) and 4‐weeks (after intervention). During study visits subjects underwent a stepped CO2 protocol, involving 5‐min stages of inspired room air, 2% CO2, 4% CO2, and 6% CO2, while measuring middle cerebral artery velocity (CBFv) using transcranial doppler ultrasound, mean arterial pressure (MAP) by finger plethysmography, ventilation, and end‐tidal CO2. Cerebrovascular conductance (CVCi) was calculated as CBFv/MAP. The reactivity of CBFv (in cm/s/mmHg), CVCi (in cm/s/mmHg2), and MAP (in mmHg/mmHg) were calculated as the linear regression slope against end‐tidal CO2 during the stepped CO2 protocol. Chemosensitivity (in L/min/mmHg) is the linear regression slope of VE vs end‐tidal CO2. Results Six healthy adults (age: 56 ± 10; 2 females) completed the study. Study visit data are displayed in Table 1. Individual training data are presented in Table 2. Following the control period there was a large reduction from baseline in CBFv reactivity [2.81 ± 1.50 to 2.03 ± 1.03; effect size 0.9], CVCi reactivity [0.020 ± 0.015 to 0.015 ± 0.010; effect size 0.7], and MAP reactivity [0.95 ± 0.63 to 0.62 ± 0.42; effect size 0.6] with no change in chemosensitivity [0.99 ± 0.68 to 0.98 ± 0.51; effect size 0.0]. Following the intervention there was no change from the 2‐week study visit in CBFv reactivity [2.03 ± 1.03 to 2.01 ± 1.09; effect size 0.0], CVCi reactivity [0.015 ± 0.010 to 0.014 ± 0.010; effect size 0.1], and MAP reactivity [0.62 ± 0.42 to 0.72 ± 0.44; effect size 0.1] with a small increase in chemosensitivity [0.98 ± 0.51 to 1.04 ± 0.53; effect size 0.3]. Conclusion Preliminary findings suggest a very brief progressive hypercapnia training program does not increase or desensitize cerebrovascular reactivity in healthy adults. These data also suggest an exaggerated cerebrovascular reactivity response may occur to an initial exposure of a stepped CO2 protocol (without familiarization), which appears to be driven by blood pressure response not chemosensitivity. Further research, particularly in populations with impaired cerebrovascular reactivity, is of interest for CBF regulation.

Introduction: Patients undergoing cardiac rehabilitation (CR) exhibit various degrees of illness severity and high prevalence of chronic conditions (CC). Cardiorespiratory fitness (CRF) is a key predictor of outcomes in patients with cardiovascular disease. Participation in CR is associated with increased CRF, reduced future cardiovascular events, and mortality. Peak oxygen uptake (VO 2 ) is the gold-standard method to evaluate CRF; however, the burden of multimorbidity and its impact on CRF improvement has not been extensively studied. Methods: We included 618 patients who were ≥ 18 years old and underwent cardiopulmonary exercise testing prior to and after CR at Mayo Clinic. Using the Rochester Epidemiology Project records- linkage system, we assessed the prevalence of 18 CC defined by the US Department of Health and Human Services. To evaluate changes in peak VO 2 in patients with multimorbidity (categorized as ≥6 CC), we created logistic regression models adjusting for age, sex, and baseline peak VO 2 . Results: Mean age was 61.5 ± 11.0 years and 75.5% were male. Most patients (81.2%) attended ≥18 CR sessions. Half (50.4%) of patients had at least 6 CC (median 6; range 0-13). Overall, peak VO 2 at baseline was 20.7 ± 6.3 mL/kg per min and the percent change in peak VO 2 following CR was 11.4% ± 21.6%, Figure 1A . Multimorbidity was associated with lower improvement in peak VO 2 following CR compared to patients with <6 CC (7.5% vs 11.4%, p=0.0001). Furthermore, across categories of CRF improvement (i.e., 1%, 5%, and 10% percent change in peak VO 2 ) lower multimorbidity was associated with a 1.5-2-fold increase in CRF when compared to those with higher multimorbidity (≥6 CC), Figure 1B . Conclusions: Patients entering CR have a high multimorbidity burden. Our results suggest that multimorbidity in CR patients attenuates improvement in peak VO 2 . Individualized interventions should focus on managing and reducing multimorbidity to minimize the negative impact on CRF improvement.

Introduction: Coronary artery disease (CAD) has been associated with cognitive decline. Cardiac rehabilitation (CR) is a class 1A recommendation for patients with CAD as it reduces future cardiac events and mortality. However, the impact of CR on incidence of mild cognitive impairment (MCI) and dementia has not been extensively studied. We investigated the association of CAD on incidence of MCI and dementia; and whether CR attendance reduces incidence of MCI and dementia in patients with CAD Methods: The Mayo Clinic Study of Aging (MCSA), a prospective, population-based cohort was probed for this study. At baseline and every 15-months thereafter, subjects were evaluated for MCI and dementia using a standardized protocol. Data on CR participation were collected via record linkage to the Rochester Epidemiology Project. To evaluate association with incident MCI or dementia, cox proportional hazard models were used and adjusted for age, sex, and clinical predictors of cognitive decline. Participants with MCI at baseline were excluded for MCI analysis and adjusted for in dementia analysis. Results: We included 5960 MCSA participants (female: 50%; age: 70±13). Of those, 1934 participants (32%) had CAD and 702 (12%) had MCI at baseline. Mean follow-up was 3.9±3.7yrs, with 760 incident cases of MCI (13%) and 290 cases of dementia (5%). CAD was a significant predictor of MCI and dementia, although after adjustment for other clinical predictors, CAD was only associated with MCI incidence ( Table 1, Figure ). Incidence of dementia was reduced in CAD patients who had a greater attendance at CR when adjusted for other predictors of cognitive decline ( Table 2 ). Attendance at CR did not reduce incidence of MCI ( Table 2 ). Conclusions: CAD was a significant predictor of MCI and dementia. In patients with CAD, a higher attendance of CR was associated with reduced incidence of dementia but not MCI. Specific CR programming and outcome targets may be needed to prevent MCI in patients with CAD.

Introduction: Cardiac rehabilitation (CR) is associated with improvements in exercise capacity (peak oxygen uptake (VO 2 peak)); however, 23% of CR patients do not improve VO 2 peak following CR. CR adherence (i.e. number of CR sessions attended) has been proposed to play an important role in VO 2 peak improvement following CR, but has not been investigated. Identifying clinical predictors of VO 2 peak improvement are critical as the degree of VO 2 peak improvement is associated with improved long-term outcomes in these patients. Purpose: To determine if clinical characteristics and number of CR sessions attended were predictive of patients who exhibited improvement in VO 2 peak following CR. Methods: Using the Rochester Epidemiology Project records-linkage system, we identified all consecutive patients >18 years old from Olmsted County, Minnesota who underwent cardiopulmonary exercise testing prior to and following CR from 1999 to 2017. Regression models were created to assess clinical predictors of VO 2 peak improvement (>0% baseline) following CR. Results: The analysis included 804 patients (75% men) with a mean age of 60.7±12.4 years. Of the 804 patients, 609 (76%) patients exhibited VO 2 peak improvement following CR. Significant univariate predictors of VO 2 peak improvement included younger age (OR: 0.99, 95% CI: 0.97-1.00), lower pre-CR VO 2 peak (OR: 0.97, 95% CI: 0.94-0.99), history of peripheral artery disease (OR: 0.48, 95% CI: 0.32-0.73), and smoking (OR: 0.63, 95% CI: 0.45-0.90). Significant independent predictors of VO 2 peak improvement from a multivariate analysis included younger age (OR: 0.98, 95% CI: 0.96-1.00), number of CR sessions (OR: 1.02, 95% CI: 1.01-1.03), lower pre-CR VO 2 peak (OR: 0.94, 95% CI: 0.91-0.96), history of peripheral artery disease (OR: 0.42, 95% CI: 0.27-0.66), and smoking (OR: 0.56, 95% CI: 0.39-0.82). Conclusions: These findings demonstrate the importance of CR adherence and individual clinical characteristics in influencing VO 2 peak improvement following CR in patients with CVD. These findings may influence the clinical practice by providing specific clinical characteristics to account for when personalizing the CR treatment plan to maximize positive outcomes.