Exercise and Cognitive Retraining to Improve Cognition in Heart Failure.

Persons with heart failure (HF) have a four-fold greater likelihood of developing cognitive impairment (CI) than their age matched healthy counterparts, placing them at high risk for adverse clinical outcomes, poorer quality of life (QOL) and higher mortality. CI is a subtle but measurable deficit in one or multiple cognitive domains; it is a deficit greater than cognitive losses associated with normal aging. The few studies that have documented CI in HF are inconsistent. Few have used standard neuropsychological testing, and little is known about change in cognitive function over time in HF. Further, if CI is detected, there are currently no effective or evidenced-based guidelines to help restore or improve cognition in this population.Despite the aging population and projected rise of CI in HF, only 2 small intervention studies have been documented, indicating a critical need for further research in this area.

The etiology of CI in HF is not fully understood, but several underlying mechanisms are consistently reported: reduced cerebral perfusion and oxygenation, brain structural changes (i.e., hippocampal damage, atrophy, loss of gray matter), and micro emboli.Clinical studies have shown that CI is improved after cardiac transplantation and is modifiable with standard therapies that improve cardiac output, oxygenation, fluid overload, and systemic and cerebral perfusion; these findings are inconsistent and anecdotal. The ability to positively influence cognitive function has important implications for patient adherence to a complex self-care regimen and the development of interventions that may partially reverse CI.

Exercise improves clinical outcomes in HF by altering the deleterious peripheral and central mechanisms that contribute to HF exacerbations, worsen symptom severity, and lead to poor clinical outcomes. Less is known about the effect of exercise on cognitive function. Animal research has provided the most compelling evidence that exercise positively affects neuronal growth and the neural systems involved in learning and memory. Similar human findings have emerged; recent advances in neuroimaging support that participation in regular exercise leads to specific changes in brain structure and function. Exercise is also thought to enhance brain plasticity. BDNF appears to play a crucial role in this process: when BDNF levels increase following exercise, cognitive function improves. The association between exercise, BDNF and cognitive function has not been previously reported in HF. This feasibility study will clarify these important relationships and increase the potential for improving clinical outcomes in a future trial.

Neurogenesis and neuroplasticity are means for the brain to recover from poor perfusion and oxygen deprivation such as that occurring in HF. Animal studies again provide the strongest evidence to date for using cognitive training (CT) to promote better cognitive functioning and provide a rationale for why a combined exercise and CT approach may be superior to monotherapy. Animal studies show that, like exercise, learning tasks and performing cognitively stimulating activities also increase BDNF levels and improve learning and memory. The effect of BDNF on brain function due to exercise however, is thought to be different from that occurring with CT. Exercise increases the proliferation and division of neuronal cells through BDNF, whereas CT appears to promote cell survival,suggesting a synergistic relationship may exist with greater benefit obtained when both are used together. The combination of exercise and plasticity-based CT has not been previously tested in HF or in other populations as an intervention for improving cognitive outcomes, but may be most optimal for targeting the underlying mechanisms for CI in HF. The proposed feasibility study is designed to test the acceptability, implementation and limited efficacy of a combined exercise (Ex) and cognitive training (CT) intervention in stable NYHA class II and III heart failure patients with cognitive impairment. A total of 60 participants will be randomized to one of three study arms: Ex/CT (N=20), Ex-alone (N=20), and attention control (N=20). The study aims are:

Aim 1: To evaluate the feasibility of a 3-arm intervention (ExCT, Ex, AC) in heart failure patients with CI.

Aim 1a. To test the acceptability and implementation of each study arm. Aim 2: To ascertain limited efficacy of the 3-arm intervention on changes in cognitive abilities Aim 3: To ascertain limited efficacy of the 3-arm intervention to improve cerebral oxygenation, physiological status, physical function and QOL.