Cognition and Exercise: General Overview and Implications for Cardiac Rehabilitation

Abstract

Performance of endurance exercise is associated with a broad range of cognitive benefits with notable improvements shown across a wide variety of populations including healthy populations as well as those with impaired cognition. By examining the effects of exercise in general populations, as well in populations where cognitive deficits are pronounced, and critical to self-care, we can learn more about using exercise to ameliorate cognitive issues and apply that knowledge to other patient populations, such as those eligible for cardiac rehabilitation (CR). Cognitive challenges are a concern within CR as management of a chronic disease is cognitively taxing, and, as expected, deficits in cognition predict worse outcomes, including lower attendance at CR. Some subsets of patients within CR may be particularly at high risk for cognitive challenges including those with heart failure with low ejection fraction, recent coronary bypass surgery, multiple chronic conditions, and patients of lower socioeconomic status. Attendance at CR is associated with cognitive gains, likely through the progressive exercise component, with larger amounts of exercise over longer periods of time having greater benefits. Programs should identify at-risk patients, who could gain the most from completing CR, and provide additional support to keep those patients engaged. While engaged in CR, patients should be encouraged to exercise, at least at moderate intensity, and transitioned to a long-term exercise regimen. Overall, CR programs are well-positioned to support these patients and make significant contributions to their long-term wellbeing.

Condensed abstract

Chronic heart disease impacts cognitive health. Cognition predicts attendance at cardiac rehabilitation and attendance is associated with cognitive benefits. Benefits are likely tied to performance of at least moderate intensity endurance exercise. Programs should support patients at high-risk for cognitive difficulties in attending cardiac rehabilitation and in maintaining exercise long-term.

Cognition and health are closely entwined. Exercise is a powerful moderator of this relationship. The purpose of this paper is to review the literature on cognition and exercise generally, as well as within populations at high-risk for cognitive deficits, with the aim of providing evidence-based guidance for cardiac rehabilitation (CR) programs.

BASICS OF COGNITION

Cognition refers to the ways that people process information and make sense of the world. There are numerous domains of cognition that put together form the basis of how people interact with other people and with perceptions to learn new ideas or processes. Cognitive deficits can have a profound impact on overall functioning and quality of life. Many illnesses lead to transient or permanent cognitive deficits that exacerbate the overall challenges related to the underlying condition.

Cognition does not simply refer to the ability to learn, but exists in numerous interrelated domains.¹ Anchored in the most basic facets of sensation and perception, broad cognitive domains including attention, memory, executive functioning (ExF), processing speed, and language skills. Within each broad domain are multiple subdomains that reflect more specific processes.¹ While many of these specific domains were initially described individually in conjunction with unique neurological lesions, the focus of this article will be on the broad, interrelated deficits such as seen in many chronic illnesses.

While there are many areas of cognition, it will be helpful to define the most prominent domains. Sensation and perception refer to the sensory inputs and basic judgments required to recognize objects and create rudimentary categories for sorting information. Attention refers to the focus on an individual item and can be further refined into selective attention on a specific item or sustained attention which looks at the ability to focus over time.

Memory, of many different types, is a major component of cognition. Of particular importance here are types of memory including working memory, or the ability to keep a particular task online and remembered while it is being completed, prospective memory which helps with recognizing and remembering how to do tasks that may arise again in the future, episodic memory which relates to the ability to remember events, and verbal memory or the ability to process and recall information presented through works (or nonverbal memory which uses other cues). There is also procedural memory which is required to call on to remember how to complete tasks. To access memories, one has to be able to encode, store, and retrieve the memories at the appropriate time.

As one processes the different types of memory, decisions must be made to keeping tasks salient and online. This process generally refers to ExF in which priorities are made for completing tasks and cognitive processes. For example, if a person is trying to accomplish three behaviors related to self-managing chronic disease (e.g. taking medications, engaging in physical activity [PA], managing appointments), they must remember all the behaviors (working memory), know how to perform the behaviors (procedural memory; e.g. I must get the pills out, swallow all three with only water), and also decide what order to complete the tasks in to maximize success (ExF; e.g. I do my best exercising in the morning, but I might miss my clinic appointment). In this higher cognitive process one must often take in new information and make adjustments requiring cognitive flexibility to best accomplish the problem solving necessary to succeed.

Cognitive domains are necessarily interrelated. In order to complete a simple or complex task, multiple cognitive systems must be engaged. For example, driving a car requires a complex and simultaneous engagement with basic sensation and perception to follow the road and note the symbols that govern the rules of driving, but also working memory (Where are you going? Why are you driving?), ExF (Which turn do you make first? Do you have multiple stops?), and processing speed to stop the car in time if something comes in the road.

TYPES OF EXERCISE

There is robust evidence supporting the use of physical exercise to improve cognition throughout a range of conditions.² There are numerous ways to engage in physical exercise. Often these are broken down into physical training and motor training subcategories, of which physical training includes endurance exercise and strength training, while motor training includes balance, flexibility, and coordination exercises.³ Developing an exercise regimen generally means including exercise of various types based upon the strengths and limitations for each individual. The different types of exercise impact the types of cognitive gains one may expect. For the purpose of this review, we will largely focus on endurance exercise as these exercises exhibit more broad cognitive impact while motor training has more direct cognitive impact related to the specifics of the exercise itself.³ Exercise is considered to be endurance in nature when the goal of the activity is to increase heart rate and cardiovascular demand necessitating an increased use of oxygen.

Benefits of Exercise on Cognition

Exercise has been shown to improve cognition over a wide range of illnesses regardless of baseline cognitive state and over a variety of time periods.⁴ Acute bouts of exercise have been shown to improve cognitive outcomes such as attention, reaction time, and inhibition⁵ while engaging in exercise over longer periods of time can slow cognitive decline.⁶ In the United States, the recommended federal guidelines for PA include 150 min/wk of moderate endurance exercise and 2 d of resistance training. Less than 23% of US adults met those standards over 2010–2015.⁷ As such, remediation of this exercise debt provides a modifiable risk factor in both cognitive and physical decline associated with aging.⁸

Focusing on physical training, endurance and resistance training, of at least moderate intensity, have been demonstrated to have a significant impact on cognition in meta-analysis.⁴ There have been trials of endurance exercise in young adults,⁹ healthy older adults,¹⁰ and in populations with numerous medical conditions including mild cognitive impairment,¹¹ Parkinson disease,¹² and schizophrenia.¹³ Schizophrenia can provide a particularly illustrative example of the effects of endurance exercise on cognition, as cognitive deficits are pronounced and exercise is one of the few available modes of treatment.

Schizophrenia is a psychiatric disorder usually characterized by the presence of hallucinations and delusions. However, the largest prognostic factors center around impairments in cognition, primarily of verbal learning, working memory, ExF, and reaction time.¹⁴ A neurodevelopmental disease, cognition tends to decrease before the onset of psychotic symptoms and can worsen over time. There are no approved medications targeting these symptoms, accordingly, other interventions have been sought to help people to maintain their cognitive functioning. Exercise, while not the only strategy,¹⁵ has been shown to enhance cognition in people from the earliest stages of the illness through to later stages, with continued research ongoing to elucidate the potential causative mechanisms for improvement.^16–18

The improvements in cognition via exercise are likely multifactorial in people with schizophrenia. One widely replicated finding has shown that exercise can reverse brain volume decreases and increases in cortical thickening.¹⁹ This is similar to findings in many other progressive neurocognitive disorders.²⁰ One putative mechanism behind these findings links improvements in exercise endurance (operationalized as change in maximal oxygen uptake [VO_2max]) with increases in brain-derived neurotrophic factor, a potent growth factor for neurons.²¹ Similarly, in people with schizophrenia, it has been shown that exercise-induced improvements in metabolic indices are correlated with improvements in cognition²² and dose of exercise is strongly correlated with benefits on cognition (r = .70, P = .015).²³ Along with the general health benefits of improved cardiorespiratory fitness (CRF), there are further implications on general functioning, with people with schizophrenia who are able to go further on the 6 min walk test having higher ratings on the global assessment of functioning.²⁴ Systematic reviews on the benefits of exercise for cognition in those with schizophrenia echo these findings, suggesting not only a strong link between amount and quality of exercise on cognitive benefits, but also connecting improved CRF to improvements in other domains, such as quality of life and global functioning.^13,25 Taken together, the link between CRF and cognition promotes many positive treatment goals for people with schizophrenia and other cognitive disorders.

Taken as a whole, the existing literature on exercise and cognition in general healthy populations, as well as from populations where cognitive deficits are pronounced, and critical to functioning and prognosis, such as in schizophrenia, can help provide insights into the issues of cognition and potential ameliorating effects of exercise in other populations, such as those eligible for CR.

CHRONIC HEART DISEASE AND COGNITION

Cardiovascular disease (CVD) continues to be a leading cause of morbidity and mortality in the US. Cardiovascular disease is highly prevalent²⁶ and claims nearly 660,000 lives/yr.²⁷ Cardiovascular disease has far-reaching implications on health, impacting multiple physiological systems, including cognition. Cognitive difficulties and impairments are over-represented in patients with CVD,²⁸ and chronic CVD is associated with declines in cognition over time. For example, a faster decline in cognitive abilities has been observed in those with coronary artery disease (CAD) as compared to adults without CAD.²⁹ Those with congestive heart failure (HF) show a similar pattern, with cognitive outcomes declining as ejection fraction decreases.²⁹ The pathophysiological explanations here are grounded in the assumption that chronic disease impacts cerebral hypoperfusion (i.e. blood supply to the brain), in turn having negative effects on cognition.³⁰ In other words, the diminished vasculature functioning that is seen among patients with chronic disease such as CAD/congestive HF leads to the cognitive impairments observed within these clinical populations.

Acute cardiac events can also impact cognition, specifically executive functioning. For example, patients who have experienced cardiac arrest (CA) are at increased risk for executive dysfunction and deficiencies in domains of memory (e.g. recall) and attention.^31,32 These deficits in cognition may result from the interruption of blood supply to the brain during CA.³² Cognition can recover following these events with most of the recovery happening within 3 mo.³¹ However, ExF seem to be most affected by these events and take longer to recover; a prospective longitudinal study found a substantial number of subjects with lingering ExF deficits at 1 yr follow-up post CA.³¹ Invasive treatment for CAD is another acute event that can negatively impact cognition; there is a well-demonstrated effect of having coronary artery bypass grafting (CABG) on cognition.³³ The adverse neurologic effects following this procedure are thought to be multifactorial, however the effects of anesthesia due to the length of the procedure and risk of brain injury have emerged as the main explanations.³⁴ These cognitive deficits generally peak shortly after surgery and usually recover within months.³⁵ Research in this area has highlighted the importance of thorough evaluation of patient risk factors (such as mild cognitive impairment at baseline) pre-operatively.³³

Cognition and Management of Chronic Disease

Self-management of chronic disease is an important component influencing quality of life and ability to self-manage may be reduced in patients with impairments in cognition. The processes and demands of managing chronic disease are likely to be cognitively taxing. Patients with a diagnosis of a chronic disease are faced with a host of new behaviors they should engage in, such as taking new medications, attending medical appointments, and engaging in more PA. They must simultaneously refrain from engaging in other behaviors that are likely deeply ingrained habits, such as smoking and eating unhealthy foods. This combination of engaging in new healthy lifestyle behaviors and inhibiting old behaviors is not easy and likely requires the cognitive processes described above as part of ExF, working memory, planning, self-control and cognitive flexibility.^36,37

Accordingly, it would be expected that cognition, and specifically ExF, would be predictive of self-management of chronic disease. Several studies appear to support this assertion. In one study, 149 adults with HF were given cognitive measures (including ExF) and self-reported adherence to recommendations for management of HF (attendance at medical appointments in the prior 3 mo, adherence to medication, exercise, and diet recommendations during the last week) with the Heart Failure Compliance Questionnaire.³⁸ Deficits in ExF (speed of processing and working memory), attention, and language were predictive of adherence to multiple areas of disease self-management.³⁸ A composite score of ExF (processing speed, working memory, cognitive flexibility) also predicted how well patients retained their participation in everyday activities following a diagnosis. In a small sample of severe congestive HF patients awaiting heart transplant, self-reported issues with ExF was found to predict reduced participation in an array of activities.³⁹

ExF has also been shown to be predictive of adherence to exercise recommendations specifically. McAuley et al studied 177 older adults (60–72 yr) and found higher levels of ExF (task coordination and inhibition of habitual response) at the start of a 12-wk exercise program were associated with higher adherence.⁴⁰ Higher ExF may also be associated with longer-term exercise maintenance, Best et al found that in a sample of women, higher ExF (inhibition of habitual response) was associated with greater adherence to PA at a 1-yr follow-up period.⁴¹

Cognition and Accessing/Adhering to Cardiac Rehabilitation

Given the association of chronic disease and cognitive issues, it should not be surprising that high levels of cognitive impairment and EF challenges are reported in some CR samples. For example, in one study of patients with acute coronary syndrome enrolled in CR > 60% of the sample had mild cognitive impairment in ≥ 1 domain at entry.⁴² Another sample of 100 congestive HF patients eligible for CR found that > 50% had ExF scores in the impaired range.⁴³ As was mentioned above, cognitive challenges interfere with the ability to manage chronic disease, and as such it would be expected that these challenges would also impact patients’ ability to access and benefit from CR. Cardiac rehabilitation is a disease management program designed to improve health outcomes in those with CVD. Cardiac rehabilitation has broad health benefits that are realized across different patient populations^44,45 and many efforts are underway to improve access to, and participation in, CR.^46–48 As such, characteristics that interfere with CR attendance require particular attention.

Several studies report that cognitive measures, such as ExF are associated with attending and adhering to activities such as CR. In one study of 114 patients undergoing cardiac surgery, preoperative frailty scores, which included measures of cognitive impairment, predicted attendance at CR.⁴⁹ In another study, the effects of ExF on attendance at CR was examined among lower-socioeconomic status patients, who are more likely to have challenges with ExF.³⁶ Multiple ExF measures (trail making task, delay discounting) were significant predictors of CR attendance and adherence, even after controlling for other variables that predict attendance. The high level of cognitive difficulties in these populations, and their effect on CR enrollment may help explain some of the challenges in enrolling all appropriate patients in CR. Issues with ExF may also translate into lower gains while in CR. In a sample of 44 patients enrolled in CR, those with lower ExF (specifically on the trail making task-B, a measure of cognitive flexibility) had lower physical fitness at exit from CR.⁵⁰

Benefits of Cardiac Rehabilitation on Cognition

There is strong support in the literature on the connections between cognitive health and regular exercise; it could be assumed that participating in a program that included structured, progressive exercise would be beneficial for cognition. Studies done thus far support this hypothesis. One of the most systematic examinations of the relationship between secondary prevention participation and cognitive benefits comes from a series of studies conducted in the context of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease. Initially, cognitive function was measured in chronic obstructive pulmonary disease patients participating in a 30-d exercise program where it was found that cognition (cognitive flexibility and psychomotor performance) improved in those who participated.⁵¹ In a subsequent study, chronic obstructive pulmonary disease patients received 10 wk of education and stress management, with half randomized to also exercise during that time period.⁵² Improvement in cognition (verbal processing) was seen only in those randomized to the exercise condition. Emery and colleagues then conducted 1 yr follow-up assessments of these patients and found that continued exercise was associated with maintenance of cognitive gains while lapse in exercise was associated with cognitive decline.⁵³ This series of studies suggests that secondary prevention that includes an exercise component can lead to cognitive improvements, that the exercise component is crucial for the cognitive gains, and that maintenance of exercise is critical for maintaining cognitive gains.

Within the population of patients with CVD, systematic reviews on the effects of exercise on cognition have been conducted, with most of the studies reviewed taking place in context of CR. One paper systematically reviewed the effects of exercise in those with vascular disease and included 12 studies in those with CVD or cerebrovascular disease.⁵⁴ All 12 studies reviewed demonstrated improvement in cognition (attention, ExF, global cognition) associated with exercise, with the greatest amount of evidence for either endurance or combinations of endurance and strength training. Additionally, 7 of the 12 studies showed a dose-dependent relationship, where greater amounts of exercise were associated with greater improvements in cognition.⁵⁴ A second systematic review examined the effects of exercise on cognition (global cognition, attention, ExF, memory and language) in those with CVD, specifically within the context of CR.⁵⁵ This study reviewed nine studies, most of which showed the same association of exercise/participation with improvements in cognition. Specifically, the most consistent improvements were seen in the areas of attention and ExF (6 of 7 studies), and memory (4 of 6 studies). Improvements were not seen in the area of language.

The type of exercise engaged in during CR may also be important. Existing literature from various domains suggests that endurance exercise is the most strongly associated with cognitive gains and the literature above suggests that dose matters, more exercise over longer periods of time will likely reap the most benefits. Additionally, intensity of exercise may be important. A recent study found better improvements in one ExF domain, cognitive flexibility, among older adults who were randomized to high intensity interval training over moderate intensity training and resistance training.⁵⁶

Generally speaking, lower CRF has been linked to cognitive dysfunction, and increases in CRF has been shown to be associated with improvements cognition, such as working memory.⁵⁵ A few mechanisms exist that may explain how sustained exercise in a CR setting improves overall cognitive outcomes. The first and perhaps most widely recognized mechanism points to redirection of blood flow from PA and resulting changes to brain structures (e.g. thickness of motor cortex)⁵⁷ and function.⁵⁸ Sustained endurance exercise leads to improvements in overall functioning and output of the heart (i.e. central hemodynamics), and these improvements are thought to contribute substantially to elements of cognition through the increase of brain blood flow. The increase in blood and nutrients to the brain may also lead to increased synaptic plasticity.⁵⁹ Combined, these processes may aid in strengthening elements of cognition such as working memory and psychomotor speed.

The functioning of certain brain regions are known to contribute to cognitive aging and function overall. For example, the hippocampus plays a crucial role processes including ExF, processing speed and working memory.⁶⁰ Increases in hippocampal neurogenesis has been observed in animal studies, such as one by Nokia et al, following aerobic and sustained physical exercise.⁶¹ While the mechanisms behind this increase in neurons is still being studied, certain mediators such as brain-derived neurotrophic factor have been proposed.⁶² Brain-derived neurotrophic factor’s main role is to regulate both excitatory and inhibitory synapses in many brain regions.⁶²

Similar to the effects of neurogenesis, increases in neuroplasticity can lead to improvements in cognition or serve as a protective factor for cognitive decline or impairment. Some studies have found a connection between PA and corticospinal excitability and intracortical circuitry. Lulic and colleagues demonstrated this connection in younger adults.⁶³ These same processes for exercise-induced plasticity could be hypothesized to occur in the CR-eligible population as well.

Cardiac Rehabilitation Patients at Increased Risk

There are subpopulations of patients within the general CR population who have demonstrated increased risk for cognitive/ExF deficits at entry into CR and may have higher attrition rates due to these deficits. The lower-socioeconomic status CVD population represents a unique group of patients who historically attend CR at a lower rate while also possessing higher prevalence of health risk behaviors (e.g. smoking) and medical comorbidities.⁶⁴ Management of chronic disease is especially challenging for these patients, as they also have higher levels of ExF challenges compared to the general CR population.⁶⁵

Patients who have undergone cardiac surgery represent another special population within CR. A relatively common complication of CABG includes post-procedure cognitive impairments. The Cache County population based study found significantly greater cognitive decline (measured by the Modified Mini Mental State) among CABG patients compared to patients without CABG at two follow-up interview timepoints.⁶⁶ Patients with pre-existing cognitive deficits who have had CABG may be especially susceptible to the impacts of this procedure and recovery on cognition.^67,68

Finally, those with multiple medical comorbidities appear to have even greater cognitive challenges than those with a single chronic disease. For example, those with both HF and chronic obstructive pulmonary disease have lower cognitive function than those with HF alone.⁶⁹ Among all of these patient subpopulations, attendance at a CR program seems critical, as participation could help ameliorate these cognitive challenges. Engagement of these cognitively at-risk populations in CR and efforts to reduce attrition should be priorities for CR programs.

APPLICATION TO PRACTICE

The existing literature on cognition and exercise lends itself to several recommendations for CR programs. First of all programs should consider screening for at-risk patients or potentially measuring cognitive outcomes. Several screening tools are available for identifying cognitive impairment such as the Montreal Cognitive Assessment (MoCA),⁷⁰ Short Blessed Test,⁷¹ the Mini Cog,⁷² as well as a novel tool for screening for multiple cognitive/neuropsychiatric concerns CAAD.⁷³ Programs could also measure ExF, however, as ExF covers a number of higher-level cognitive functions, it would be recommended to measure aspects of ExF that are of particular interest. For example, the trail making task B portion of the Delis-Kaplan EF system measures an aspect of ExF (cognitive flexibility) that seems to predict attendance at CR as well as improve as a function of CR attendance. Delay discounting is another measure of an aspect of ExF that can be calculated rather quickly and provides an estimate of how a patient values short-term vs. long-term gains, and is predictive of participation in health-related behaviors, including adherence to CR.^34,74

In regard to exercise modality, the data is fairly robust. While many types of exercise seem beneficial, the best evidence is for endurance exercise, of at least moderate intensity, with regular sessions over longer periods of time (weeks to months) associated with better outcomes. Evidence for the session length needed is mixed. While there is some evidence that ≥ 20 min of exercise in a bout are needed for the best acute cognitive outcomes in healthy young adults,⁷⁵ evidence in older adults suggest that it is the total volume of exercise (dose*frequency) that is important for longer-term cognitive outcomes.⁷⁶ High-intensity interval training has been shown to improve CRF when applied appropriately in CR,⁷⁷ and some evidence suggests it may have similar positive effects for cognition.⁵⁶ Finally, given the likely necessity of maintenance of exercise for maintenance of cognitive gains, plans for transition to a Phase 3 CR, community, home exercise, or mobile health maintenance program are highly recommended. If longer-term programs are not available staff should focus on helping patients build skills to help maintain exercise following completion of CR.

Recommendations can also be made around supporting at-risk patients. Programs should be aware of patient populations where cognitive/ExF challenges are overrepresented such as those with multiple chronic diseases, low ejection fraction HF patients, CABG patients, and lower socio-economic status patients. Patients at risk may need extra support in attending and adhering to CR, but also may have the most to gain from participation. One possible patient support could be using case-managers to guide patients through the process of getting started in CR, identifying barriers to attendance, providing reminders of appointments, and organizing transportation as needed.⁴⁶ Processes that reduce the burden of accessing and adhering to CR should benefit these at-risk populations disproportionately.

Findings from existing and on-going studies of exercise programs for people with schizophrenia provide additional ideas for ways to improve uptake and adherence to exercise recommendations as well as highlight challenges. We have found that when presented with entertaining forms of exercise, such as active-play video games, participants were very likely to attend sessions regularly (81% adherence in our initial study).⁷⁸ Further, as the subjects often worked out in small groups, they began to form connections with each other that helped further propel their adherence and may yield further downstream benefits on socialization (observed anecdotally). Unfortunately, maintaining exercise regimens in participants after conclusion of the research has proven challenging. Access to safe places to exercise, as well as to the active-play video games or individual/group trainers, can be limited. This mirrors many of the challenges with instituting exercise programs in the general community.⁷⁹

SUMMARY

Deficits in cognition are overrepresented in medical populations and these deficits can interfere with self-management of disease. Data from studies from a variety of perspectives show substantial benefits of exercise on cognition. On-going and existing studies in populations where cognitive deficits are prevalent and critical to self-care (e.g. schizophrenia) suggest that the dose, supervision, and enjoyment of exercise are important to consider when using exercise to support cognitive health.^11,23 Cognitive challenges are also a concern within the context of CR. Patients with cognitive challenges may struggle to participate in CR, yet also could have the most to gain from attendance. Programs should seek to identify these patients and provide additional support to keep them engaged in CR. While engaged in CR, to support cognitive health, patients should be encouraged to exercise at moderate intensity, as tolerated, and at a length of time and frequency that maximizes total exercise volume. High-intensity interval training may provide particular benefit for those able to follow that method of endurance exercise. Long-term maintenance of cognitive gains will likely require maintenance of exercise as well, so transitioning to long-term exercise plans after primary CR is critical. Overall, with sufficient investment and attention, CR programs are well-positioned to support patients to exercise and make significant contributions to their long-term wellbeing.

Table 1.

Summary of Reviewed Findings

Cognitive Measures that may Predict Adherence to Health-Related Behaviors

Attention

Language

Mild cognitive impairment

Executive function

Working memory

Processing speed

Cognitive flexibility

Inhibition of habitual response

Delay discounting

Self-reported problems with Executive Function

Cognitive Measures that may Improve with Sustained Endurance Exercise

Attention

Memory

Global Cognition

Psychomotor performance

Verbal processing

Executive function

Cognitive flexibility

Working memory

Inhibition of habitual response