Heart & Lung 44 (2015) 120e128

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Computerized auditory cognitive training to improve cognition and functional outcomes in patients with heart failure: Results of a pilot study Ponrathi Athilingam, PhD, ACNP, MCH, FAANP a, *, Jerri D. Edwards, PhD b, Elise G. Valdes, MS b, Ming Ji, PhD a, Maya Guglin, MD, PhD c a

College of Nursing, University of South Florida, USA School of Aging Studies, University of South Florida, USA c Cardiovascular Medicine, University of Kentucky, Lexington, USA b

a r t i c l e i n f o

a b s t r a c t

Article history: Received 14 April 2014 Received in revised form 16 December 2014 Accepted 17 December 2014 Available online 12 January 2015

Objectives: Feasibility and efficacy of computerized auditory cognitive training (ACT) was examined among patients with heart failure (HF). Background: Individuals with HF have four times increased risk of cognitive impairment, yet cognitive intervention studies are sparse. Methods: A pilot randomized controlled design was used. Results: The ACT group (n ¼ 9) and control group (n ¼ 8) had similar baseline characteristics. Seven participants (78%) completed 18 hours of ACT. Medium effect sizes were observed for improved cognition as indicated by auditory processing speed (d ¼ 0.78), speech processing (d ¼ 0.88), and working memory (d ¼ 0.44e0.50). Small effect sizes were found for improved functional outcomes including HF selfcare (d ¼ 0.34), Timed Instrumental Activities of Daily Living (d ¼ 0.32), Six-Minute Walk Test (d ¼ 0.38) and Short-Form-36 (d ¼ 0.22) relative to controls. Conclusion: Results indicated ACT is feasible among persons with HF. Despite a small sample size, ACT showed potential for improved speed of processing and working memory and improved functional outcomes, and warrants further exploration. Ó 2015 Elsevier Inc. All rights reserved.

Keywords: Heart failure Cognitive training Cognitive impairment Speed of processing Memory Self-care

Introduction Heart failure (HF) is a progressive disease affecting 5.7 million Americans.1 Over 80% of HF patients are older than 65 years of age.2 Older adults with HF have four times higher risk of having cognitive impairment as compared to the general population,3 which challenges their daily self-care ability.4,5 Cognitive difficulties such as speed of processing, memory, attention, and executive function are clearly evident among persons with HF.6,7 Furthermore patients with HF are expected to learn complex information about self-care, which can be challenging and frustrating.2,3 Our previous study identified some degree of cognitive impairment among 54% of HF participants.6 Such cognitively impaired patients with HF are 30%

Conflict of interest: From June to August 2008, Dr. Edwards worked as a limited consultant to Posit Science who, currently markets the “Brain Fitness” program. No other authors have conflicts of interest. * Corresponding author. Tel.: þ1 8139747526; fax: þ1 8139749324. E-mail address: [email protected] (P. Athilingam). 0147-9563/$ e see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.hrtlng.2014.12.004

more likely to have poor self-care,8e10 medication adherence,11,12 and quality of life.13e15 Additionally, such patients delay seeking medical care for HF symptoms,16e18 and have higher mortality rates.19 Although multiple cognitive intervention studies in older adults have demonstrated improvements in cognition,20,21 there is scant research on interventions to improve cognitive function among patients with HF,22 which could potentially improve selfcare. Therefore, a pilot randomized controlled study was conducted to explore the feasibility of a computerized auditory cognitive training (ACT) program in patients with HF. The potential efficacy of the intervention to improve cognitive and functional abilities was explored. Thus, the aims of this exploratory study were to examine feasibility and explore potential efficacy of ACT among patients with HF.

Theoretical and scientific background The model of adult cognitive plasticity supports the use of ACT to enhance cognition.23 This model indicates that exercises that are

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adaptive in difficulty are required for the brain to experience an appropriate mismatch between abilities and environmental demands and induce plasticity-based changes in the brain.23 According to this model, computerized cognitive interventions such as ACT, which include exercises that are continually adaptive to the users’ ongoing performance, are needed to enhance cognition. Adaptive cognitive training techniques ensure a continued mismatch between ability and task demands by continually adjusting task difficulty based on performance.23 ACT is a processbased, adaptive program, which requires the practice of auditory information processing.24,25 The exercises in ACT are designed to be challenging with difficulty customized to each individual user in order to create an appropriate mismatch between the user’s abilities and the demands of the program. Process-based cognitive training targets basic information processing, resulting in greater cognitive improvements and wider transfer to improved everyday function than other cognitive training approaches.24,25 The information degradation theory further supports the notion that process-based cognitive interventions, such as ACT, which target perceptual information processing (See Table 1), will be most effective to improve cognitive function.25 The information degradation hypothesis posits that errors in initial perceptual processing cause difficulties with higher-order cognition. If initial perceptual processing can be improved (e.g., processing speed, speech processing), then higher cognitive function (e.g., working memory) should also improve. ACT may be particularly effective by incorporating an auditory component, which plays a crucial role in the upstream delivery of information and precipitates better cognitive function.25 Cognitive training with ACT is presumed to enhance cognitive function through the practice of adaptive exercises of perceptual processing resulting in improved cognitive efficiency from plastic alterations of the brain.24 ACT may enable the brain to better receive, process, store and utilize auditory information24 which can result in more efficient processing for higher order functions such as attention and memory.24,25 ACT could be a viable intervention approach for persons with HF who are expected to learn and remember complex information for appropriate HF selfcare. Cognitive training is well-established as an effective approach to counter age-related cognitive decline among relatively healthy older adults. One of the largest clinical trials examining the efficacy of cognitive interventions among healthy older adults (N ¼ 2832) demonstrated that a process-based cognitive intervention (similar to ACT but with exercises in the visual domain) resulted in large effect sizes for enhanced cognitive speed of processing relative to control conditions.26 The cognitive gains derived from training were evident at 5- and 10-years later.27,28 This process-based speed of processing training transferred to improved functional outcomes

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including health-related quality of life, protection against depressive symptoms, improved locus of control, and reduced predicted health care costs.29e32 At 10-years, those randomized to the process-based cognitive intervention reported the least difficulty with instrumental activities of daily living (IADLs).27 ACT is a very similar process-based training approach, but with exercises in the auditory domain. To our knowledge, three studies of ACT have been conducted to date, but only one among patients with HF. A multi-site randomized trial among healthy older adults (N ¼ 487) showed that ACT improved auditory memory, attention, as well as self-report of everyday cognitive function compared to active controls (p’s < 0.05)20 with sustained improvements in memory and processing speed at 3-months.21 ACT has also been investigated in a pilot study among 47 older adults with mild cognitive impairment.33 Results indicated that of those randomized to ACT, 77% successfully completed ACT at home and demonstrated small effect sizes for improved verbal learning and memory, but not for language or visuospatial function as compared to an active control condition.33 Recently, Pressler and colleagues conducted a pilot study of ACT in adult patients (21 years of age or older) with systolic HF (N ¼ 40).22 Patients were randomized to ACT or HF education. Results indicated significant improvements in delayed recall (p ¼ 0.015), and working memory (p ¼ 0.029).22 The authors indicated that there was a trend for improved performance of IADLs, which included deciphering medication schedules and understanding nutritional values from food labels.22 According to the information degradation theory, ACT will be effective by improving basic perceptual processing (i.e., auditory processing speed, speech processing). Pressler and colleagues did not examine auditory processing speed or speech processing. The working memory outcome in this prior study was an experimental version with visual stimuli rather than the traditional version with auditory stimuli.22 The effects of ACT on functional outcomes such as HF self-care, performance-based function [e.g., Timed IADL; Six Minute Walk Test (6MWT)], physical and mental health measured by Short-Form-36 (SF-36) were not examined by this prior research. Since research utilizing ACT in persons with HF is sparse, the present pilot study examined the feasibility and explored potential efficacy of the ACT program among older adult patients with systolic and diastolic HF who had not been diagnosed with dementia. Unlike prior research, we examined auditory processing and speech perception as outcomes. If, according to the information degradation theory, ACT enhances cognition by improving the brain’s ability to better receive, process, store, and utilize auditory information, enhanced auditory processing and speech perception should be evident. We also expanded upon prior studies by

Table 1 Summary of ACT exercises. Frequency sweeps Tell us apart

Match it

Sound replay

Listen and do Story teller

Participants are asked to identify order of tone sweeps of high and low speech syllables. The sweeps gets faster encouraging faster sound processing to help the brain respond to even the quickest speech. Potential cognitive concepts addressed include auditory processing speed. Participants are provided with discriminate speech syllables, like ‘do’ and ‘bo’; ‘dah’ and ‘pah’; ‘rake’ and ‘bake’. These syllables are presented with decreasing differences between syllables at an increasing speed. The goal is to help interpret and process speech and store clear memories, thus improve working memory. Potential cognitive concepts addressed include speech processing, memory and working memory. Participants are required to identify and remember the location of sounds on a spatial grid in order to match them. These sounds will appear on the spatial grid with increasing number of items and speed as participant progress through the exercise. This will help to improve speed of processing and thus improve memory. Potential cognitive concepts addressed include auditory processing speed and memory. Participants are asked to remember and identify order of words presented with an increasing number of words and speed. The goal is to improve the ability to engage in and remember conversation. Potential cognitive concepts addressed include auditory processing speed, speech processing, and memory. Participants are required to remember and follow instructions with increasing complexity and speed with a goal to improve working memory. Potential cognitive concepts addressed include auditory processing speed and working memory. Participants are expected to comprehend stories as the story length and speed increase, thus promoting stronger memory for details and improved communication abilities. Potential cognitive concepts addressed include auditory processing speed, speech processing, and memory.

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examining functional outcomes including performance-based measures relevant to individuals with HF. We hypothesized that ACT would be feasible among HF patients. Feasibility was examined in two ways. First, we examined the proportion of individuals with HF who completed the study (75% or more). Second, among those randomized to ACT, we examined the percentage who successfully completed at least 18 h of training.34,35 We hypothesized that compared to the control condition, the patients with HF randomized to ACT would demonstrate improved auditory processing speed, speech perception, and working memory; thus potentially leading to improved HF-related functional outcomes (e.g., HF self-care, Timed IADL, 6MWT, and SF-36). Effect sizes for cognitive and functional outcomes were calculated and examined. Methods Design A pilot, randomized controlled trial design was utilized to compare ACT to a control group that received standard HF care. The university’s Institutional Review Board approved the study. Subsequent to HF hospital admission, participants were consented and screened before randomization. Data were collected at baseline and at 16 weeks. Participants randomized to ACT completed the intervention in their homes with a goal of completing 40 h. All participants who completed the 16-week follow-up were included in analyses. Inclusion and exclusion criteria of the sample The inclusion criteria were designed based on prior cognitive intervention studies to ensure that the participants could properly perceive and understand the testing and training stimuli.27,34 Inclusion criteria were: 1) clinical diagnosis of HF as defined by the International Classification of Diseases (ICD-9 codes), 2) able to speak, understand and read English, 3) New York Heart Association (NYHA) classification IIeIV, 4) not listed for heart transplant as status 1A, 5) not enrolled in a palliative or hospice care program, 6) no major, uncontrolled psychiatric disorders, 7) no history of stroke or other neurological disorder, 8) able to hear at 70 dB at 1 and 2 kHz (screened utilizing an Audioscope, Welch Allyn), and 9) no evidence of dementia. Computerized cognitive interventions such as ACT are designed to counter normal age-related decline and mild cognitive impairment.20,21,24,35,36 Such brain fitness programs are not appropriate for persons with dementia due to exercise difficulty as well as the reduced brain plasticity that occurs with the onset of dementia.23,24 Therefore, the Montreal Cognitive Assessment (MoCA) was used for cognitive screening to determine evidence of dementia.37 Participants with a score below 20 (indicating dementia) were excluded, since these individuals may not properly perceive and understand the testing and training stimuli. The MoCA is a cognitive screening measure with a Cronbach’s alpha 0.8337 and has been validated for use in HF.6 Hertzog recommends pilot study among at least 20 participants to reasonably estimate feasibility.38 Thus, the goal was to enroll 20 participants who met these criteria.

are designed to simulate realistic listening contexts in a graduated fashion, moving from simple to complex auditory stimuli. Within each exercise, the stimuli become less discriminable and speed of presentation increases as performance improves. These six exercises are summarized in Table 1. Participants randomized to ACT were informed that over time, the speed, difficulty, and complexity of each task would systematically increase as users successfully attained specified performance criteria built into the program. Participants were encouraged to use the program for 30e60 min a day for 5 days a week with a goal of completing up to 40 h of ACT in 16 weeks. Usage and trial-by-trial data of ACT were automatically recorded and uploaded to a secure server. Individuals continued training at home for 16 weeks or until 40 h of training were completed, whichever occurred first. Participants were given noise-reducing headphones to use with ACT at home. The wait-listed control group received standard medical therapy during the first 16 weeks and was provided access to ACT after follow-up data collection. Participants who did not own a home computer or have home internet access were loaned a computer, as was done in the IMPACT trial.20,21 Variables and measures Measures were categorized as: feasibility outcomes, primary cognitive-behavioral outcomes, and secondary functional outcomes. Demographic and clinical variables including age, education, HF severity (measured by ejection fraction and NYHA class), HF etiology (ischemic or non-ischemic), HF medications, and co-morbidity data (Modified Cumulative Illness Rating Scale)39 were collected from chart review. Feasibility outcomes We used two indices to measure the feasibility of ACT; the percentage of participants who completed the study, and among those randomized to ACT, the number of training hours completed. Molloy and colleagues assert that requiring 80% of participants with HF to complete a study is too stringent.40 Therefore, we chose 75% of participants completing the study as the first criterion to indicate feasibility. Furthermore, we expected at least 75% of the participants randomized to ACT to complete the training in order to indicate feasibility. Training adherence criterion was set at completing 90% of the recommended 20 h (18 h), as was done in the protocol of Edwards’ and colleagues cognitive training study.34 This criterion was somewhat more stringent than prior cognitive training studies that have considered completing 80% or more of prescribed training hours to indicate adherence.36,41,42 This is further justified in that among patients with HF, adherence to widely prescribed angiotensin converting enzyme inhibitors has been reported as 80% over a one-month period.43 Furthermore, we chose this criterion because Edwards et al found that an average of 15 h of process-based cognitive training was effective for enhancing cognition.44 However, there is a clear doseeresponse relationship with process-based cognitive training, so more training should result in better outcomes.45 Therefore, the criterion of completing 18 h of training was chosen as the outcome to demonstrate feasibility.

Intervention: auditory cognitive training (ACT) Cognitive behavioral outcome measures ACT involves perceptual practice of information processing exercises and stimulates the auditory processing system with a goal of improving higher order functions such as attention and memory.20,21 ACT consists of six auditory exercises aimed at enhancing speed and accuracy of auditory processing. The exercises

Cognitive difficulties in speed of processing, memory, and executive function (e.g., working memory) are evident among persons with HF.4,7,46 Such cognitive difficulties result in poor functional performance and negative health outcomes.8e10

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Individuals with HF are expected to remember and apply a great deal of information for adequate HF self-care. ACT may improve cognition at a basic perceptual level (i.e., ability to process, understand, recall, and apply self-care instructions) translating to enhanced function. ACT may enable the brain to better receive, process, store and utilize auditory information,24 which would be reflected by improved processing speed and speech processing. These basic cognitive improvements can result in more efficient processing for higher order functions such as working memory.24,25 The cognitive-behavioral measures for this study were novel to ACT research and include speech perception and auditory processing speed (i.e., ability to process and understand instructions), which are targeted by ACT, as well as auditory working memory. Auditory processing speed was assessed using the time compressed speech test (TCS) with the Northwestern University (NU) No. 6 word list at 45% and 65% compression. The words were spoken by a female speaker.47 A total of 50 words for each compression condition were presented binaurally and scored as the percent of correct responses for a maximum score of 100, with higher scores indicating better performance.47 Reliability for this test has been established with intra-class coefficients of 0.58e0.87.48 Such measures of auditory temporal processing are targeted by ACT and have been directly related to higher-order cognitive processing. The Speech Perception in Noise (SPIN) test was used to measure speech processing (i.e., ability to process and understand instructions), which is targeted by ACT.49 The SPIN is composed of multiple lists presented binaurally with different signal-to-noise ratios (SNR) at 4 dB decrement. A total percent correct as well as SNR for 50% performance are calculated to arrive at a score that ranged from 2.5 to 24.5 with lower scores indicating better performance. SPIN has a reliability coefficient of 0.92.49 The participants were asked to repeat the last word in the sentence from each list. For this study, the SPIN was presented at SNR 8 dB in the first list, and 4 dB in the second list with the speech track set at 50 dB. Each list was presented with 100 target words and different speech babbles. The auditory N-Back task was used to measure working memory (i.e., ability to process and recall information), which is targeted by ACT. This measure is reliable and valid with Cronbach’s alpha ¼ 0.93 and has been in use over 50 years.50 Participants were asked to monitor the identity of a series of verbal auditory stimuli and to indicate when the currently presented stimulus is the same as the one presented in either one or two trials prior.50 Performance was assessed in terms of accuracy, that is the proportion of hits minus false alarms, for the 1-back and 2-back conditions.51 Higher scores indicate better performance with fewer misses and false alarms.51 The previous study of ACT in HF examined a visual working memory task.22 Secondary outcomes: functional measures Special efforts were also directed toward measuring the realworld impact of intervention using functional measures relevant to HF. Functional measures novel to the study of ACT included HF self-care, Timed IADL, 6MWT, and SF-36.22 HF self-care behavior was assessed using the modified HF SelfCare Behavior Scale.52 This validated measure has a 5-point Likert scale with 9-items and has a Cronbach’s alpha of 0.81. A total possible score of 45 is calculated on the basis of all positive answers and a lower score indicates better self-care behavior.52 In completing the Timed IADL, respondents were guided, via auditory instructions, through a standardized timed assessment of performance of five instrumental visual activities of daily living: finding a telephone number for a given individual in a residential phone directory, finding and counting out correct change, finding

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and reading out the first three ingredients on a can of food, finding two specific food items on a shelf of food, and finding and reading the directions on a medicine container.53 All tasks used a standardized set of stimulus materials. The test has a retest reliability of 0.64. Scoring is based on a combination of speed and accuracy for each task, with lower scores for better performance.53 This measure is novel to study of ACT in HF. Objective functional capacity was measured using the 6MWT.54 Distance walked during the 6MWT (200 m) is a strong predictor of mortality and HF readmission,55 and is moderately inversely related to NYHA class.54 The 6MWT complements the functional assessment measured by NYHA classification to determine severity of HF with good predictive validity that best reflects the activities of daily living and is generally well tolerated by persons with HF.56 The American Thoracic Society guidelines for conducting the test was strictly adhered to during data collection.57 Distance walked in 6 min in meters was measured with longer distances walked indicating better functional performance. The short form (SF-36)Ò of the RAND Medical Outcome Study (MOS) questionnaire was used to evaluate participants’ general physical and mental health of all participants.58 The SF-36Ò Health Survey measures the following eight health concepts, which are relevant across age, disease and treatment groups: 1. physical functioning, 2. role limitations due to physical health problems, 3. bodily pain, 4. general health, 5. vitality (energy/fatigue), 6. social functioning, 7. role limitations due to emotional problems and mental health (psychological distress), and 8. psychological wellbeing. The standardized scoring system yields a profile of eight health scores, two summary measures, a self-evaluated change in health status and a total score.58 The higher the score the less disability, for example a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability or perfect score.58 For this study, we used the standard (4-week) questionnaire. Demographic and clinical data, as well as co-morbidity data (using the Modified Cumulative Illness Rating Scale)39 were collected from medical records of all consented participants. Study procedures The participating cardiologists referred potential participants to the study coordinator, a registered nurse (RN), who contacted the patients at Tampa General Hospital, and referred the patients to the PI, an advanced practice registered nurse (APRN) at the University of South Florida (USF) HF clinic. Participants were informed of the requirements regarding screening for eligibility, randomization, and data collection. Voluntary participation was emphasized prior to participants signing the informed consent. Once consented, participants were screened. If deemed eligible, they were scheduled for a 2-h visit within 30 days for baseline data collection, randomization, and intervention or a waiting period. The research assistant (RA), a doctoral student, administered cognitive testing as well as functional assessments at the Cognitive Aging Lab. Eligible participants were block randomized in groups of three to either ACT or a wait-list control condition (who received standard medical care): thus the first three participants (1e3) were assigned to ACT and the next three (4e6) were assigned to the wait-listed control condition. For those randomized to ACT, the RA created an anonymous log in and password for accessing ACT from the secured web site. The RA was available for all participants via phone as needed to clarify concerns throughout the training period. The RA called all participants from both conditions weekly to maintain contact between visits and to offer support and encouragement. Postintervention data were collected at 16 weeks from both groups regardless of training adherence.

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Data analysis

Table 2 Sample characteristics of the participants at baseline.

To examine feasibility, the percentage of participants who completed the study, and among those randomized to ACT, the number of training hours completed was determined. Efficacy of ACT was explored by determining effect sizes on the cognitive and functional outcomes. Baseline descriptive statistics were computed for demographic and clinical variables. Participants who completed the follow-up visit from both conditions (ACT n ¼ 8; wait-listed control group n ¼ 6), regardless of the number of training sessions completed were compared utilizing t-tests and Chi-square analysis. Repeated measures ANOVA compared the ACT and wait-listed control groups across time (baseline to post-test) to examine the effects of training. Effect sizes were calculated utilizing Cohen’s d as the mean difference from baseline to post training gains between the ACT and wait-listed control groups, divided by the baseline standard deviation of the wait-listed control group.59 Results Enrollment and randomization Twenty-eight potential HF participants were approached with a goal to enroll 20 participants. Of the 28 potential participants approached, four declined to participate (primarily due to being too busy). Four participants did not meet the inclusion criteria. Three participants were ineligible due to MoCA scores 0.15). All of the participants were on a prescription for beta-blockers, and all either had a prescription for angiotensin converting enzyme (ACE) inhibitor (71%) and/or angiotensin receptor blocker (ARB, 29%). See Table 2 for demographic data differentiated by group at baseline. With regard to available data on age-adjusted norms for cognitive outcomes, 21e29% of the sample performed worse than average on TCS.48,60 Feasibility assessment

Figure 1. Enrollment table.

The first criterion for feasibility of ACT was set as 75% of enrolled participants completing the study based on evidence from previous HF studies.40 The final analytic sample of the pilot study included 82% (14 of 17 participants enrolled); eight in the ACT group and six in the wait-listed control group who completed the study at 16 weeks. Hence, ACT may be feasible in the HF population.

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Furthermore, we expected at least 75% of the participants randomized to ACT to complete at least 18 training hours in order to indicate feasibility.34,44 Given that 78% of those randomized to ACT completed 18 h or more of cognitive training at home, on their own, the ACT is potentially feasible in this population. Potential efficacy for cognitive function Consideration of statistical significance is not appropriate given the small sample size. Analyses were conducted to determine effect sizes to inform future clinical trials. Repeated measures ANOVAs comparing the ACT and control groups across time were conducted for each cognitive outcome. The group  time interaction effect size indicates the magnitude of the training effects, comparing the two groups across baseline to post-test. Results are summarized below and reported in Table 3. The results from this pilot study on intervention effects are exploratory and only those who completed the follow-up visits are included in the analyses below. Participants randomized to the ACT group showed potential improvements in certain cognitive performance outcomes including auditory speed of processing and speech processing (TCS 65%, SPIN SNR 4 dB), and working memory (N-Back conditions). The auditory processing speed measured by TCS at 65% compression increased by 3.12 points in the ACT group, while the control group declined by 13 points. The speech in noise perception performance at the 4 dB condition indicated a mean score change of 0.86 points improvement in the ACT group while the control group declined 1.6 points. The working memory N-back 1 score improved by 1.63 points and the N-back 2 score improved by 4.25 points in the ACT group, while the control group declined. See Table 3. To examine the potential benefits of ACT on cognitive outcomes, effect sizes were calculated utilizing Cohen’s d. The results indicated medium to large effect sizes for possible improvements from ACT on most of the cognitive outcomes. Notable medium to large effect sizes were observed for auditory processing speed (TCS 65%, d ¼ 0.78), speech processing (SPIN SNR 4 dB, d ¼ 0.88), and working memory (N-Back 1, d ¼ 0.50; N-Back 2, d ¼ 0.44). Potential efficacy for HF functional outcomes Repeated measures ANOVAs comparing the ACT and control groups across time were conducted for each functional outcome to examine the group  time interaction effect size. Across all

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functional outcomes measured, the ACT group showed potential for improvement relative to controls. Participants in the ACT group declined slightly (1.25 points) in the HF self-care score, while the control group declined more than twice the ACT group (3.16 points). The performance-based IADL assessment indicated that those in the ACT group tended to be faster and more accurate at post-test while the control group declined in speed and accuracy, as reflected by the composite standardized scores. The objective physical functional measure, 6MWT, improved 78 m in the ACT group compared to a decline of about 10 m in the control group. Similarly, among those randomized to the ACT condition, SF-36 general physical and mental health improved by 1.62 points compared to a decline of 2.67 in the control group. To examine the potential benefits of ACT on functional outcomes, effect sizes were calculated utilizing Cohen’s d. The results indicated small effect sizes for potential improvements from ACT on all of the functional outcomes. Small effect sizes were observed for HF self-care (d ¼ 0.34), Timed IADL (d ¼ 0.31), 6MWT (d ¼ 0.37), and SF-36 (d ¼ 0.22), relative to controls. Discussion Feasibility of ACT The results indicated that cognitive intervention with ACT is potentially feasible among patients with HF. Eighty-two percent (n ¼ 14) completed the study at 16 weeks follow-up. The dropout rate in our study is similar to that reported in a larger cohort of cardiac patients at 29.2%.61 Among high risk patients the dropout rates from clinical trials are reported to be 30e50%.62,63 A review of 71 randomized controlled trials in four top medical journals reported dropout rates of 20% or more.64 Molloy and colleagues found that across 16 randomized trials in persons with HF, 79.8% on average completed the studies with a range of 28%e100%.40 Barnes et al similarly found that in a patient population with mild cognitive impairment, 77% of participants completed a study of ACT.33 Thus our 82% completion rate is to be expected for this population. Furthermore, seven out of nine participants (78%) randomized to ACT completed at least 18 h of training at home, on their own. Prior study and recent work in our lab has indicated that 15 h of process-based training may be needed to obtain immediate transfer of training to functional outcomes.33,44 A recent meta-analysis indicates that at least 10 h of cognitive training are needed to

Table 3 Cognitive and functional outcomes from Auditory Cognitive Training (ACT) of participants who completed baseline and 16-weeks follow-up. Brain fitness ACT (n ¼ 8) Baseline Mean  SD Cognitive outcomes TCS 45% TCS 65% a SPIN 3 a SPIN 4 N-Back 1 N-Back 2 Functional outcomes HF Self-care a TIADL 6MWT-meters SF-36 total

Wait-listed control (n ¼ 6) 16 weeks Mean  SD

Baseline Mean  SD

16 weeks Mean  SD

Sig p

Effect sizes (d)

88.88 58.13 0.49 7.03 25.12 15.75

     

14.16 23.28 4.28 12.81 8.27 8.87

79.62 61.25 0.50 6.16 26.75 20.00

     

31.09 24.42 1.83 10.58 8.79 6.26

80.33 50.67 1.6 5.1 27.0 20.67

     

20.99 20.54 2.13 3.03 2.28 1.51

73.67 37.67 2.1 6.9 27.5 20.33

     

22.03 31.33 3.86 4.30 1.38 5.96

0.74 0.07 0.73 0.11 0.38 0.09

0.123 0.784b 0.230 0.881b 0.495b 0.436b

24.25 0.26 309.13 51.75

   

2.66 1.08 247.04 28.71

23.00 0.07 387.75 53.37

   

6.23 0.77 229.93 24.08

24.33 0.17 496.3 65.17

   

5.57 0.59 232.3 19.32

21.17 0.02 487.8 62.5

   

6.08 0.68 184.07 29.19

0.61 0.19 0.23 0.66

0.343b 0.315b 0.382b 0.222b

AVLT: NU No.6: Northwestern No.6; SPIN: Speech Perception In Noise; HF: heart failure; TIADL: Timed Instrumental Activities of Daily Living; 6MWT: Six Minute Walk; SF-36: Short-Form 36. p values reported are from the repeated measures ANOVA group  time interaction. a Lower scores reflect better performance. b Effect size indicates potential improvement from ACT.

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receive benefit.65 Thus, ACT is considered potentially feasible in the HF population. This assertion is further justified in that among patients with HF, adherence to widely prescribed angiotensin converting enzyme inhibitors has been reported as 80% across 30days and diminishes to 60% at one-year.43 Therefore, given the acceptable dropout rate and adherence of the ACT condition, cognitive intervention with ACT among patients with HF is considered potentially feasible. Potential efficacy of ACT The results from this pilot study demonstrate that the intervention with ACT is likely to improve cognitive performance in working memory (N-back). The clinically meaningful effect sizes for cognitive outcomes are not well established.66 However, conventionally effect sizes of d ¼ 0.5 or larger are considered meaningful. Moderate to large effect sizes were also evident for improved speed of processing (TCS at 65% compression), and speech processing (SPIN with SNR at 4 dB). This means that the participants who used ACT may potentially be able to take in and process information (such as speech) more quickly than before. The working memory test (N-back) is perhaps the most challenging of the cognitive outcomes measured. Similarly, for auditory processing speed and speech processing, potential improvements were only seen in the most challenging subtests. Interestingly, across these measures, performance declines were noticed in the control condition, while the ACT group experienced potential performance improvements. Other studies of cognitive training have shown similar results when examining older adults with some degree of initial cognitive impairment33,36,41,42 as may be expected in HF patients. The results of this study are unique in that the cognitive outcomes measured are targeted by ACT to strengthen and build auditory processing speed and memory. According to the information degradation theory,25 such perceptual information processing improvements should result in improved cognitive functioning upstream. Further research with a larger sample is needed to determine if cognitive improvements from ACT mediate functional improvements. Cognitively impaired persons with HF are 30% more likely to have inadequate self-care8e10 and poor quality of life.13e15 Across all functional outcomes measured, those randomized to ACT showed potentially better functional outcomes than the control group. The control group participants tended to show twice the rate of decline in HF self-care as did those in the ACT condition. Thus, ACT may potentially reduce or prevent declines in self-care. Those in the ACT condition showed potential improvements in objective functional measures such as the Timed IADL and 6MWT and general physical and mental health (SF-36), while the control group showed potential decline. The potential benefits of ACT on these HF specific outcomes warrant further exploration in a larger sample. Results shed light on the need for further investigation of cognitive interventions such as ACT to determine if cognitive impairments experienced by persons with HF may be attenuated to enhance HF outcomes. Evidence from similar cognitive training among older adults suggests that cognitive training effects remain evident over time21,27,28 and may be associated with lower health care expenditures across five years.29 Heart failure by its very nature leads to frequent hospital admissions due to the complexity of the disease and its progression. However, these repeated hospital admissions may be partly related to cognitive impairment that may negatively affect self-care and decision making to seek care for HF symptoms.4e6,8,9,17 Cognitive interventions should be easy to use by older adults and cognitively challenged patients with HF. ACT is easy to use as it requires only basic computer skills, can be self-administered at home, and may

be an ideal cognitive intervention tool. Interventions to enhance cognition as a means to improve HF outcomes have only recently been explored.22 However, similar cognitive interventions among older adults without HF,24,26e28,67 patients with MCI,33,68 multiple sclerosis,69,70 Parkinson’s disease,34,71,72 and HIV73 have been successful. Cognitive remediation is an innovative approach to address critical barriers to progress in HF care. A larger study is needed to fully explore the benefits of ACT in HF. Data from this pilot study showed the potential benefits of ACT to enhance key cognitive functions that may transfer to improved specific HF outcomes including self-care relative to controls. Interventions that include components specifically geared toward improving self-care in patients with HF warrant further exploration. Limitations A major limitation of this study was the small sample size recruited from one facility. This exploratory study included many outcome measures and the sample size was not adequately powered. The purpose was to examine feasibility and explore potential efficacy across several outcomes that were novel to ACT to inform future research. One of the most contentious aspects of trial design is selection of the comparison group. We included a wait-listed control group to assess benefits of ACT. Use of an active control group is preferred.74,75 Hence, future studies should include an active control design to fully evaluate benefits of ACT. Due to the small sample size we did not consider significance testing. Future studies should use an intent-to-treat analysis in a larger sample modeling for attrition. We used self-reported measures for HF selfcare that may lead to bias.76 However, performance based outcomes such as the Timed IADL and 6MWT indicated potential improvement in the ACT group while the control group experienced potential decline. Clinical implications and conclusions Despite increased prevalence of cognitive impairment among patients with HF,3e7 current core performance measures and the AHA guidelines do not recommend cognitive screening and/or cognitive intervention to improve HF outcomes.77,78 Cognitive impairment could negatively affect patient’s abilities to carry out self-care, potentially resulting in higher hospital readmission rates; yet cognitive impairment has been overlooked as a critical factor in the clinical management of HF. Under the Affordable Care Act, the Center for Medicare and Medicaid Services developed a formula and assigned a benchmark on hospital reimbursement for readmissions, inflicting heavy burdens on hospitals.79 Therefore, the hospital system has been working on strategies to reduce 30-day readmission rates by improving HF performance measures.80 In a large retrospective study (N ¼ 6063) the 30-day readmission rate was not associated with adherence to performance measures.81 This perplexing issue of high 30-day readmission rate most likely cannot be solved through hospital performance measures and current disease management programs. Evidence indicates benefits of cognitive training for older adults can last as long as 10 years.27 However, research is sparse in patients with HF to determine benefits of cognitive training in improving self-care and thus reduce readmission rates. Studies that demonstrated improvement in HF clinical outcomes have targeted patients without cognitive impairment. Recently, among 125 HF patients with mild cognitive impairment self-care was not associated with HF education.82 The potential for individuals with HF to improve their cognition by cognitive training is intriguing and needs to be more fully explored. Our work is in accord with prior claims that engaging in complex

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mental activity may offer ways to enhance cognition and promote health related outcomes.27,67 Improvement in cognition may potentially enhance HF outcomes including self-care, quality of life, hospital readmission rates, and associated costs. A larger, longitudinal, randomized controlled study is warranted to evaluate ACT.83 Researchers need to explore if cognitive training improves functional outcomes in HF. Positive results could be translated into effective and sustainable public health programs and policies throughout the nation.

Acknowledgment Sarah Eisel for her professional editing service.

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