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Gender Differences in Cognitive Test Performance in Adults With Heart Failure

Rochette, Amber D. BA; Spitznagel, Mary Beth PhD; Sweet, Lawrence H. PhD; Cohen, Ronald A. PhD; Josephson, Richard PhD; Hughes, Joel PhD; Gunstad, John PhD

The Journal of Cardiovascular Nursing: May/June 2017 - Volume 32 - Issue 3 - p 212–217
doi: 10.1097/JCN.0000000000000330
ARTICLES: Heart Failure
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Background: Cognitive deficits are found in up to 73% of persons with heart failure (HF) and are associated with increased mortality and other poor clinical outcomes. It is known that women have better memory test performance than men do in healthy samples, but gender differences in cognitive performance in the context of HF are not well understood and may have important clinical implications.

Objective: The objective of this study was to examine possible gender differences in cognitive function in a sample of individuals with HF (98.9% New York Heart Association class II and III).

Methods: A total of 183 adults with HF (116 men and 67 women) completed a neuropsychological test battery as part of a larger project. Measures were chosen to assess functioning in attention/executive function and memory.

Results: After controlling for demographic and medical factors, multivariate analysis of covariance revealed that men and women differed on memory test performance (λ = 0.90, F4, 169 = 4.76, P = .001). Post hoc comparisons revealed that women performed better on California Verbal Learning Test Learning, Short Recall, and Delayed Recall. No differences emerged on tests of attention/executive function (λ = 0.97, F5, 168 = 0.96, P = .44).

Conclusions: In this sample of persons with HF, men exhibited poorer performance on memory measures than women did. Future studies are needed to determine the underlying mechanisms for this pattern and its possible influence on daily function.

Amber D. Rochette, BA Graduate Student, Department of Psychological Sciences, Kent State University, Ohio.

Mary Beth Spitznagel, PhD Assistant Professor, Department of Psychological Sciences, Kent State University, and Clinical Psychologist, Department of Psychiatry, Summa Health System, Akron, Ohio.

Lawrence H. Sweet, PhD Professor, Department of Psychology, University of Georgia, Athens.

Ronald A. Cohen, PhD Professor, Department of Aging & Geriatric Research, University of Florida, Gainesville.

Richard Josephson, PhD Professor of Medicine, Harrington Heart & Vascular Institute, University Hospitals Case Medical Center, and Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio.

Joel Hughes, PhD Professor, Department of Psychological Sciences, Kent State University, Ohio.

John Gunstad, PhD Professor, Department of Psychological Sciences, Kent State University, Ohio.

This work funded by the National Institutes of Health (HL089311).

Dr Gunstad reports grants from the National Institutes of Health during the conduct of the study. The other authors have no conflicts of interest to disclose.

Correspondence John Gunstad, PhD, Department of Psychological Sciences, Kent State University, 144 Kent Hall, Kent, OH 44242 (jgunstad@kent.edu).

Heart failure (HF) is a significant public health problem, as an estimated 5.1 million Americans are currently living with the condition, and this prevalence is expected to increase an additional 46% by 2030.1 Heart failure is associated with many adverse health outcomes, including functional decline, reduced quality of life,2 recurring hospitalization, and increased mortality.3 In addition to these health consequences, HF is an established risk factor for cognitive impairment,4 particularly in domains of memory, attention, and executive function.5,6 Cognitive deficits are found in up to 73% of HF patients4,7,8 and are independent predictors of premature mortality, rehospitalization, and functional decline.9,10

Much research has been devoted to elucidating gender differences in the etiology, presentation, and prognosis of HF. Data suggest that men are more likely to develop HF, do so at a younger age,11 and have poorer prognosis.12 However, women are more likely to exhibit reduced quality of life,13 depression,14 higher pain levels, and sleep difficulties.15 Less is known about possible gender differences in neurocognitive outcomes in HF.

Results from studies in healthy populations and other cognitively declining samples suggest that gender differences may exist in the context of HF. In healthy cohorts, gender differences in cognitive function are commonly reported, with women outperforming men on verbal learning and memory tasks.16–19 However, no differences are consistently found on measures of attention and executive functioning.18,19 Other work has found that women maintain this cognitive advantage in a cognitively declining sample with atherosclerosis.20

Despite these findings, few studies have directly examined possible gender differences in cognitive function in persons with HF. In 1 study of persons with HF (ejection fraction, 28.2 ± 10.3), men exhibited poorer test performance in multiple domains, including memory, psychomotor speed, and visuospatial recall, despite having less severe HF.6 Such findings encourage further examination, particularly in persons with milder forms of HF (eg, New York Heart Association [NYHA] class II and III). Based on the above study, we hypothesized that HF would be associated with poorer cognitive function in men relative to women.

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Methods

Participants

The current sample was composed of 183 adults (116 men and 67 women) with HF who were enrolled in a larger project examining neurocognitive outcomes in HF.21 All participants were stable ambulatory patients receiving routine clinical care at Summa Health System in Akron, Ohio. To be eligible for the study, persons must have been between 50 and 85 years of age at the time of enrollment, be English-speaking, and have an NYHA class between II and IV (98.9% NYHA class II and III). Exclusion criteria included history of neurological disorder (eg, dementia, stroke), head injury with more than 10 minutes loss of consciousness, presence of a severe psychiatric disorder (eg, schizophrenia, bipolar disorder), substance abuse and/or dependence, and renal failure. See Table 1 for baseline demographic and clinical characteristics.

TABLE 1

TABLE 1

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Measures

Cognitive Function

Commonly used neuropsychological measures were used to quantify cognitive test performance. These measures are well established, have strong psychometric properties, and have been recommended for use in persons with cardiovascular disease.22 Raw scores for each measure were used in the primary analyses and were categorized into 1 of 2 neuropsychological domains. Specific measures included the following:

Attention/executive function: Trail Making Test A23 has individuals rapidly draw a line connecting numbered circles, and completion time is used as a measure of complex visual scanning and psychomotor speed. Trail Making Test B24 asks individuals to quickly connect alternating numbers and letters in ascending order, and completion time is used as a measure of ability to shift and maintain cognitive set.

The Frontal Assessment Battery25 is a short measure consisting of 6 subtests that assess frontal mediated abilities. The Word and Color Word trials from the Stroop Color Word Test26,27 were administered. The Word trial has individuals rapidly read the names of colors printed in black ink. The Color Word trial asks participants to indicate the color of ink a word is written in, ignoring the actual word, which spells out a different color. The number of words read aloud in 45 seconds for each trial is used as a measure of selective attention and mental flexibility.

Memory: The California Verbal Learning Test-II requires participants learn, recall, and recognize a 16-item word list. Four indices from the California Verbal Learning Test-II were used to quantify memory, namely, Sum of Learning Trials 1–5, Short Delay Free Recall, Long Delay Free Recall, and Total Recognition Hits.28

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Physical Fitness

The 2-minute step test (2MST) asks individuals to lift their knees above a marked target during a 2-minute period.29 This measure of physical fitness was included as a covariate, as research indicates that fitness levels are independently associated with cognitive function in people with HF.30 This fitness estimate has been found to correlate with standard treadmill stress testing in persons with HF.30

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Demographic Characteristics

Medical and demographic characteristics were ascertained through a combination of self-report and medical record review.

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Procedures

Participants were informed of the research study by staff at Summa Health System. Interested participants then provided consent to be contacted by a research assistant. The local institutional review board approved the study procedures and all participants provided written informed consent before initiation of any activities. During a single assessment, participants completed the 2MST and demographic and psychosocial self-report measures. Participants were also administered the neuropsychological test battery. The visit occurred at a time convenient for the participant, typically in midmorning or early afternoon. Medical records were later examined to supplement self-report and corroborate all available information. All procedures were performed in a hospital setting by trained research assistants and under the supervision of a licensed clinical neuropsychologist.

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Statistical Analyses

Statistical differences in demographic and medical conditions between men and women were examined using t tests and χ2 tests. Before primary analyses, assumptions for inferential statistics were examined and met, including separately by gender. Multivariate analysis of covariance was used to compare cognitive test performance, adjusting for any demographic and medical characteristics that differed between groups. Raw scores from each neuropsychological test were used in the analyses. To further clarify gender differences in cognitive test performance, raw scores from each cognitive test were transferred to T scores using existing norms and used to calculate prevalence of cognitive impairment in the sample. Cognitive impairment on a specific test was defined as a T score of 35 or lower. χ2 Analyses compared the prevalence rates of impairment on a specific task within 1 of the primary cognitive domains (ie, attention/executive function, memory) or any impaired test performance.

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Results

Demographic and Medical Differences Between Men and Women

Women had lower educational attainment (t181 = 3.09, P = .002), were less likely to have a history of smoking (χ21 = 5.79, P = .02), had higher ejection fraction (t181 = 2.46, P = .02), and had poorer estimated fitness levels (2MST; t1 = 2.06, P = .04) than men did (see Table 1). Women also trended toward a higher likelihood of hypertension (χ21 = 3.77, P = .05) but were less likely to have history of bypass or valve surgery (χ21 = 3.01, P = .08) or history of myocardial infarction (χ21 = 3.26, P = .07). Given these findings, between-group comparisons for cognitive test performance were adjusted for age, education, ejection fraction, 2MST, hypertension, history of bypass/valve surgery, history of myocardial infarction, and history of smoking.

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No Gender Differences in Attention/Executive Function

Multivariate analysis of covariance was conducted on tests of attention/executive function while adjusting for age, education, ejection fraction, 2MST, hypertension, history of bypass/valve surgery, history of myocardial infarction, and history of smoking. In terms of covariates, a significant influence of age (λ = 0.86, F5, 168 = 5.38, P < .001), education (λ = 0.90, F5, 168 = 3.90, P = .002), hypertension (λ = 0.92, F5, 168 = 2.90, P = .02), and 2MST (λ = 0.87, F5, 168 = 5.20, P < .001) emerged. However, analyses found no effect for gender, such that men and women with HF did not differ on tests of attention/executive function (λ = 0.97, F5, 168 = 0.96, P = .44; Table 2).

TABLE 2

TABLE 2

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Gender Differences in Memory Performance

Multivariate analysis of covariance was then conducted on tests of memory while adjusting for age, education, ejection fraction, 2MST, hypertension, history of bypass/valve surgery, history of myocardial infarction, and history of smoking. In terms of these covariates, a significant influence of age (λ = 0.85, F4, 169 = 7333, P < .001) emerged. This analysis also found an effect for gender, such that men and women with HF differed on tests of memory (λ = 0.90, F4, 169 = 4.76, P = .001; see Table 2). Bonferroni-corrected post hoc tests showed that women performed better than men did on Sum of Trials 1–5 (F1, 172 = 18.10, P < .001), Short Delay Free Recall (F1, 172 = 9.80, P = .002), and Long Delay Free Recall (F1, 172 = 12.89, P < .001). No differences emerged for Total Recognition Hits (F1, 172 = 1.92, P = .17).

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No Gender Differences in Prevalence of Cognitive Impairment

Analyses indicated that men and women with HF did not differ in prevalence rates of cognitive impairment in attention/executive function, memory, or any impaired test performance (P > .05 for all; see Table 3).

TABLE 3

TABLE 3

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Discussion

Past research demonstrated that gender differences in cognitive functioning exist in persons with moderate to severe HF.6 The current study sought to examine whether a similar pattern is found in a sample of HF patients with predominantly NYHA class II and III. After adjusting for possible confounds, results showed that women performed better than men did on multiple memory indices, although no differences emerged on measures of attention/executive function.

As hypothesized, women performed better than men did on tasks of memory in this sample of adults with HF. Women exhibit better memory test performance than men do in healthy older populations16,19,31 and APOE4 carriers,32 suggesting that the current findings may reflect this premorbid advantage. However, it is also possible that specific aspects of HF might contribute to gender differences in cognitive functioning. For example, men develop HF at a younger age,33 and the cognitive effects of some medical conditions (eg, type 2 diabetes, obesity, hypertension) are known to increase over time.34–36 Even though men and women were generally similar in their current HF status (and statistical adjustments were used for all analyses), it is possible that historical aspects of HF that vary by gender may also influence cognitive outcomes (ie, age at onset/duration, lowest ejection fraction, severity and number of myocardial infarctions, smoking history, combination of comorbid conditions, etc). It is also possible that HF leads to differential structural and functional brain changes in men and women. A series of projects from Woo and Kumar37–40 have revealed that HF is associated with abnormalities on neuroimaging, including greater atrophy (including structures like the hippocampus and caudate), reduced cortical thickness, and changes in mean diffusivity. Although gender differences have not yet been directly examined through these studies, preliminary findings suggested this possibility.40,41 Data from large, epidemiological studies will help clarify possible mechanisms for the observed gender differences in cognitive function and the reason they are limited to memory test performance.

Despite these group differences in performance, follow-up analyses found no differences in the prevalence of cognitive impairment (T score < 35) within domains. These findings suggest that men and women with HF are both susceptible to memory dysfunction, but men experience more severe levels of impairment. As above, the exact mechanism for this pattern is unclear and may involve novel risk factors for cognitive impairment in persons with HF. If confirmed, such findings may help to account for the increased mortality risk in men with HF,11 as cognitive impairment in HF populations is linked to diminished self-care behaviors and performance in instrumental activities of daily living,9,42,43 which are known to exacerbate HF symptoms and prognosis.44,45 Given that research suggests even mild cognitive dysfunction may impact self-care in this population46 and the high prevalence of cognitive impairment in both genders in this sample, routine cognitive screening in HF should be explored as a means of improving functional outcomes.

The current study is limited in several important ways. First, all data used for this study were cross-sectional, and a prospective study using a closely matched control group is needed to elucidate the pattern of cognitive decline in male and female HF patients. Results in this study may also be affected by the methodological and statistical limitations of the current study, including unequal sample of men and women and inclusion/exclusion criteria. For example, this study excluded individuals with history of known neurological disorder and lacked information on other factors (eg, HF duration, HF type, timing, and specific severity of cardiac events) that should be accounted for in future studies, as they may help to clarify the cognitive profile in this sample.

In summary, the current study found gender differences in cognitive function in persons with HF. Specifically, women had better performance than men did on measures of memory, although no differences were found in prevalence of cognitive impairment. The mechanisms underlying these findings are unclear and warrant further investigation. Better understanding the patterns of cognitive impairment in men and women with HF may help clarify the etiology of gender differences in the presentation and prognosis of HF. Elucidating these relationships is essential to improving clinical treatment and outcomes for both genders.

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What News and Important

  • Cognitive impairment is common in persons with HF.
  • In this sample, men with HF exhibited poorer scores on measures of learning, short delay, and long delay free recall than women did.
  • Routine cognitive screening in HF should be explored as a means of improving functional outcomes for both genders.
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Keywords:

cognitive function; gender characteristics; heart failure

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