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Psychosomatics 48:22-30, February 2007
doi: 10.1176/appi.psy.48.1.22
© 2007 Academy of Psychosomatic Medicine
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Effects of Antidepressant Treatment on Cognitive Performance in Elderly Subjects With Heart Failure and Comorbid Major Depression: An Exploratory Study

Tânia C.T.F. Alves, M.D., Ph.D., Jairo Rays, M.D., Ph.D., Renata M.S. Telles, M.D., Renério Fráguas Júnior, M.D., Ph.D., Mauricio Wajngarten, M.D., Ph.D., Belkiss W. Romano, M.Sc., Cintia Watanabe, B.A., and Geraldo F. Busatto, M.D., Ph.D.

From the Department of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; and the Division of Geriatric Cardiology and Division of Psychology , Institute of the Heart, University of São Paulo Medical School, São Paulo, Brazil. Send correspondence and reprint requests to Tânia C.T.F. Alves, M.D., Ph.D., Centro de Medicina Nuclear, Hospital das Clínicas da FMUSP, Rua Dr. Ovídio Pires Campos s/n – 3. Andar, CEP 05403-010, São Paulo-SP Brazil. e-mail: tania_alves{at}hotmail.com


  ABSTRACT

 
TOP
 ABSTRACT
INTRODUCTION
 METHOD
 RESULTS
 DISCUSSION
 REFERENCES
 
Cognitive deficits are common in association with heart failure (HF), and it is possible that their severity is magnified by the concomitant presence of major depressive disorder (MDD). Using the Cambridge Mental Disorders of the Elderly Examination battery, the authors compared the cognitive performance of MDD–HF subjects (N=20), nondepressed HF subjects (N=23), and healthy control subjects (N=18). Scores were lower in both HF groups relative to control subjects. In the MDD–HF group, there were significant cognitive improvements after antidepressant treatment. Cognitive impairment is, therefore, significant in HF subjects with or without comorbid MDD, and it is important to recognize and treat MDD symptoms associated with HF.


  INTRODUCTION

 
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 ABSTRACT
 INTRODUCTION
METHOD
 RESULTS
 DISCUSSION
 REFERENCES
 
Heart failure (HF) is a highly frequent and incapacitating disorder in the elderly population.1 Cognitive impairment is one of the most prevalent features associated with this cardiac condition,2 reported in approximately 25% of patients discharged from the hospital after treatment for HF and independently predicting higher levels of functional disability.3

Studies detailing the patterns of cognitive deficits associated with HF have been limited in number. There is evidence that the cognitive impairment in patients suffering from severe HF is global,4 whereas subjects with mild-to-moderate HF may present more circumscribed deficits in anterograde memory and information-processing domains.5

One issue that remains to be clarified is the possible impact of depressive symptoms on the profile of cognitive deficits associated with HF.6 There is frequent comorbidity of major depressive disorder (MDD) and HF,7 and this comorbidity is associated with increased number and duration of hospitalizations for HF treatment, as well as higher death rates.8 Because cognitive deficits are known to be highly prevalent in idiopathic MDD, particularly in elderly subjects,9 it is possible that the presence of depressive symptoms could significantly magnify the cognitive impairment seen in association with HF. However, no study to-date has specifically assessed the impact of depressive symptoms on the patterns of cognitive deficits associated with HF. Neither has there been a direct investigation of whether effective treatments for MDD symptoms could have a positive impact on the cognitive performance of subjects with HF.

In this study, we compared the cognitive performance of HF subjects, functional classes II and III of the New York Heart Association (NYHA), divided in two groups according to the presence of comorbid MDD, with that of a control group of healthy elderly volunteers. We predicted that the comorbidity with MDD would be associated with significantly greater overall cognitive impairment in HF patients. Also, we wished to investigate whether the cognitive decline observed in MDD–HF subjects could be significantly improved with antidepressant treatment and reversal of the major depression status.


  METHOD

 
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 ABSTRACT
 INTRODUCTION
 METHOD
RESULTS
 DISCUSSION
 REFERENCES
 
Study Sample and Assessment Schedules
Local ethics committees approved the study, and written informed consent was obtained from all subjects after a complete description of the study.

A total of 190 consecutive HF cases from the Division of Geriatric Cardiology of the Institute of the Heart, University of São Paulo Medical School, were screened by cardiologists between the years 1999 and 2000. Patients were potentially eligible for the present study if they had chronic symptoms of HF currently classified in the functional classes II or III of the NYHA and if they had been stable on an optimized cardiologic medication regimen for at least 1 month before the evaluation. The presence and severity of HF were determined by detailed cardiological anamnesis, physical examination, ECG, and echocardiographic left-ventricular ejection fraction (LVEF) below 50%. Patients were ineligible if they had a history of myocardial infarction within the past 3 months or hospitalization for cardiovascular disease within the past month, if there were signs of carotid obstruction at physical examination, if they had a history of alcohol abuse, or if they were currently using psychoactive drugs, including benzodiazepines, mood stabilizers, or antidepressants.

A total of 116 HF patients were found to be potentially eligible according to the above criteria, but 18 refused to take part in the study. The remaining 98 HF subjects were assessed for the presence or absence of MDD according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV),10 based on information obtained with the Structured Clinical Interview for DSM-IV–Patient Edition (SCID–I/P).11 On the basis of the SCID–I/P results, patients were divided into an MDD–HF group (N=46) and a nondepressed HF group (N=52).

Patients in the two HF groups above were excluded from the current study if they fulfilled one or more of the following additional exclusion criteria: personal or first-degree family history of neurodegenerative disorders; personal history of other major psychiatric conditions as assessed with the SCID–I/P; and first-degree family history of major psychiatric disorders, including MDD. Such exclusion criteria were needed to allow us to investigate, without the influence of confounders, the relationship between cognitive deficits that could be assumed to be secondary to HF (rather than due to other causes) and major depressive symptoms that could be assumed to be directly linked to the consequences of HF (rather than reflecting a vulnerability to depression that manifested itself before or independently of the onset of HF).

In the nondepressed HF group (N=52), 14 patients were excluded because they had a previous history of MDD, 8 fulfilled DSM-IV criteria for dementia, and 5 fulfilled DSM-IV criteria for current generalized anxiety disorder or panic disorder. In the MDD–HF group (N=46), 10 patients were excluded as they indicated the presence of MDD before the diagnosis of HF, 5 fulfilled DSM-IV criteria for dementia, and 2 had previous episodes of mania. From the remaining 29 MDD–HF subjects, 8 were excluded because their depressive symptoms were classified as mild, according to the 31-item Hamilton Rating Scale for Depression (Ham-D);12 (Ham-D scores <18). Among the excluded HF patients, two subjects from the MDD–HF group and five subjects in the nondepressed HF group were also ineligible because they had at least one first-degree family member with a history of major psychiatric or neurodegenerative disorder.

The total of 72 potentially eligible HF subjects who did not eventually take part in the study had a mean age of 75.14 years (standard deviation [SD]: 6.15 years), a mean LVEF of 36.4 (SD: 5.7), and a gender distribution of 43 male/29 female subjects. Their HF was due either to ischemic heart disease (N=34) or dilated cardiomyopathy (N=38). Such demographic and clinical characteristics were similar to those of the HF subjects selected for the study (presented in Table 1). A proportion of the excluded HF subjects had a personal history of hypertension (N=54; 75.0%), diabetes (N=24; 33.3%), and atrial fibrillation (AF; N=19; 26.4%). We also interviewed 50 subjects from the local community in order to select the healthy-comparison group. Subjects were eligible if they had no symptoms suggestive of HF or psychiatric/neurological disorders detected on general medical questioning, physical and neurological examination, and interviewing with the SCID–I/P. Nine healthy subjects refused to take part in the study; 10 had a previous history of psychiatric disorders (anxiety and/or major depression), 5 had a history of alcohol or benzodiazepine abuse/dependence, 3 fulfilled DSM-IV criteria for dementia, and 4 had a diagnosis of current MDD. Among the excluded healthy-control subjects, three were also ineligible because they had at least one first-degree family member with a history of major psychiatric or neurodegenerative disorders. The remaining 19 healthy volunteers were selected for the control group.


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TABLE 1. Demographic and Clinical Features of Heart Failure (HF) Patients and Healthy-Control Subjects



A structural brain scan was acquired in 21 MDD–HF patients, 17 nondepressed HF patients, and all the 19 control subjects selected for the study. In nine MDD–HF patients, seven nondepressed HF patients, and four healthy-control subjects, computed tomography (CT) scans were obtained; in the remaining subjects, structural MRI data were acquired, using a 1.5-tesla GE Signa LX-Cvi scanner (General Electric; Milwaukee, WI). For the subjects who were examined with MRI, visual semiquantitative ratings for white-matter hyperintensities (WMH)13 were compared among MDD–HF patients, nondepressed HF patients, and healthy-control subjects. This analysis, reported elsewhere, showed no differences in WMH ratings among the three groups, although a significant direct correlation was detected between the severity of frontal periventricular WMH and Ham-D ratings in the MDD–HF group.14 There were two MDD–HF patients with neuro-radiological signs of lacunar infarcts, a finding that is in accordance with the known significant risk of such brain lesions in association with advanced age and the diseases underlying HF.15 We did not exclude a priori these subjects from the current study, nor any subjects with signs of dilated lateral ventricles (which were noticeable in mild-to-moderate degrees at visual inspection in a greater proportion of subjects with HF relative to the healthy-control group); this decision was made so as to avoid making our study groups poorly representative of the average HF population. However, one subject in the MDD–HF group and one subject in the healthy-control group were excluded because of the presence of cortical infarcts detected by MRI scanning, because such lesions could determine the cognitive profile presented by those patients; this exclusion resulted in a final sample size of 20 cases in the MDD–HF group, 23 subjects in the nondepressed HF group, and 18 subjects in the healthy-control group.

The MDD group had HF due to either dilated cardiomyopathy (N=10) or ischemic heart disease (N=10). The mean duration of the present MDD episode was 8.8 (SD: 6.4 months), and they had a history of 1.6 (SD: 0.6) previous episodes of MDD (data based on information obtained with the SCID–I/P). The diagnosis of HF preceded the emergence of MDD in all subjects. Nine of these subjects had been treated with psychopharmacological agents in the past, but they were all without antidepressant treatment for at least 1 month before the study. The nondepressed HF group included 12 subjects with HF due to dilated cardiomyopathy and 11 patients with ischemic heart disease. None of the nondepressed HF subjects had a previous history of MDD. The pharmacological treatment for both HF groups included the use of angiotensin-converting enzyme inhibitors (ACEI; N=40), beta-blockers (N=15), diuretics (N=10), salicylates (N=17), and statins (N=4). Ten HF subjects were also receiving digoxin and anticoagulant therapy for the treatment of AF, and 17 patients were taking oral antidiabetic agents. Nitrates were also used in 10 HF patients with ischemic coronary disease that presented with angina. The HF subjects with concomitant hypertension (N=42) were treated with the same drugs as indicated above for HF symptoms. In the control group, 10 subjects were under pharmacological treatment for hypertension with beta-blockers (N=1), ACEI (N=6), or diuretics (N=3), and 6 subjects were taking oral antidiabetic agents.

There were no significant differences with regard to age, gender distribution, social class, and years of education, either between the overall HF sample and controls, or between the two HF groups (Table 1). There were significant differences between the total HF group and the healthy-comparison group with regard to history of hypertension and mean current values of LVEF, but these variables did not differ significantly between the depressed and nondepressed HF subjects (Table 1). The MDD–HF group presented lower mean current systolic blood pressure values as compared with both nondepressed HF patients (p=0.05) and control subjects (p<0.001; Table 1).

The cognitive test battery included the Mini-Mental State Exam (MMSE),16 and all subscales of the section for assessment of cognitive functioning from the Cambridge Mental Disorders of the Elderly Examination (CAMCOG).17 The CAMCOG is a brief neuropsychological battery designed to assess the range of cognitive functions required for a diagnosis of dementia, as well as detect mild degrees of cognitive impairment. It is divided into several subscales, which assess individual cognitive domains, including orientation, language (expression and comprehension), memory (recent and remote), learning, attention, praxis, calculation, abstract thinking, and perception.18

Antidepressant Treatment in the MDD–HF Group
After the initial clinical and neuropsychological evaluation, the MDD–HF patients were submitted to a 2-week placebo-treatment period and then treated with selective serotonin-reuptake inhibitor antidepressants (SSRIs) for 8 weeks. Two MDD–HF patients died during this period from complications of their cardiac condition. Thirteen patients completed the treatment trial with citalopram (initial dose: 20 mg; mean dose at 8 weeks: 5.38; SD: 8.77), and the remaining five were treated with sertraline (initial dose: 50 mg; mean dose at 8 weeks: 70.00; SD: 27.38). In both subgroups, antidepressant doses were increased at 4 weeks if there were residual depressive symptoms. Treatment outcome was evaluated by use of Ham-D scores measured at 8 weeks after treatment initiation. Posttreatment evaluation was blind in the citalopram-treated HF subjects because these were being included in a double-blind, placebo-controlled trial evaluating antidepressant response in HF patients; in the sertraline-treated subgroup, one prescribing psychiatrist, who was responsible for all five patients, obtained non-blind Ham-D ratings. Treatment response was assessed as the percent of Ham-D change, with subjects classified as treatment responders (when there was at least a 50% decrease in Ham-D score), partial responders (20%–50% Ham-D decrease), or nonresponders (Ham-D decrease <20%). The CAMCOG re-evaluation of MDD–HF patients was also conducted after 8 weeks, with the investigator blinded for improvement in depression symptoms. For a required power of 80% to detect approximately 15% improvement in cognition from pretreatment scores after remission of MDD,19,20 and considering that the standard deviation (SD) of total CAMCOG ratings in groups such as ours may approach 10% of the mean score,21 we calculated that at least 17 MDD subjects would be required to complete the posttreatment CAMCOG evaluation at a one-tailed significance level of 0.05.

Statistical Analysis
Data were analyzed with the Statistical Package for Social Sciences for Windows (7.5.3 Version). We conducted between-group comparisons of pretreatment cognitive performance (in MDD–HF versus nondepressed HF patients and healthy controls), using analyses of variance (ANOVA) with Tukey post-hoc comparisons. In order to verify which demographic and clinical variables most significantly influenced the cognitive test scores in the overall HF group, we conducted a multiple-regression analysis, using the pretreatment total CAMCOG score as dependent variable, and LVEF, Ham-D scores, gender, age, history of AF, smoking habits, and presence or absence of diabetes as independent factors ("enter method"). The investigation of significant changes in total CAMCOG scores after antidepressant treatment in the MDD–HF group was carried out using paired t-tests. We also compared separately, by use of t-tests, the scores on each CAMCOG subscale among groups before and after treatment as an exploratory investigation aimed at ascertaining whether MDD-related cognitive deficits were widespread or circumscribed to specific domains, in order to generate hypotheses for future studies.

With the aim of verifying whether the same pattern of cognitive impairment would emerge in the HF subjects who were definitely free from silent brain infarcts and other gross lesions, we repeated the above statistical analyses, comparing the cognitive performance among the MDD–HF group, the nondepressed HF group, and the healthy-control group, after excluding the subjects whose neuro-radiological examination revealed signs of lacunar infarctions (N=2), as well as those who did not undergo either the CT or MRI evaluation (N=6).


  RESULTS

 
TOP
 ABSTRACT
 INTRODUCTION
 METHOD
 RESULTS
DISCUSSION
 REFERENCES
 
Cognitive Assessment Before Antidepressant Treatment
Table 2 shows the cognitive test data for the three groups before antidepressant treatment. Significant differences in total CAMCOG scores were detected among the groups of MDD–HF patients, nondepressed HF subjects, and healthy-controls (F[2]=125.52; p<0.001). Tukey post-hoc comparisons showed that there were significant CAMCOG score differences both between MDD–HF patients and nondepressed HF subjects (mean difference: –17.54, SD: 2.92; p<0.001; 95% confidence interval [CI]: –24.55 to –10.52), and between nondepressed HF subjects and healthy-controls (mean difference: –12.08, SD: 3.00; p<0.001; 95% CI: –19.30 to –4.86). In the exploratory investigation of separate CAMCOG subtests among groups, the nondepressed HF group showed, compared with controls, cognitive deficits in the domains of learning, recent memory, language expression, attention, and language comprehension (the following t values are "greater than"): (t = –2.354, df: 39, p<0.024); the MDD–HF group showed significantly lower scores than control subjects in all CAMCOG subscales (t = –2.33, df: 36, p<0.025), and lower scores than nondepressed HF subjects in the following domains: learning, language, remote memory, praxis, calculation, abstract reasoning, and perception (t = –2.25, df: 41, p<0.030).


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TABLE 2. Cognitive Test Scores in Heart Failure (HF) Patients Before Antidepressant Treatment and Healthy-Control Subjects



The multiple-regression analysis showed an overall significant association between total CAMCOG scores in HF subjects and the demographic and clinical variables entered (R2[11, 49]=0.690; F=9.929, p<0.001). The individual regression coefficients were statistically significant only for the relationship between CAMCOG scores and Ham-D scores (standardized regression coefficient: –0.492; standard error: 0.131, df: 60, t = –4.916, p<0.001); and the LVEF (standardized regression coefficient: –0.549, standard error: 2.245, df: 60, t = –3.089, p=0.003). There were no significant correlations between pretreatment CAMCOG scores and age (p=0.072), gender (p=0.920), history of AF (p=0.166), smoking habits (p=0.955), arterial blood pressure (p=0.811), history of hypertension (p=0.811), and history of diabetes (p=0.344).

Cognitive Performance of Depressed HF Patients After Antidepressant Treatment
There was a considerable reduction in Ham-D scores in the MDD–HF patients (N=18) who completed the 8-week treatment trial with SSRIs (mean Ham-D reduction: 64.9%; SD: 4.2%). Thirteen of these patients were considered treatment-responders, four were partial responders, and one was classified as nonresponder.

There was a statistically significant increase in total CAMCOG scores (61.83; SD: 14.29; t[17] = –5.029; p<0.001) in the MDD–HF group after treatment. Exploratory paired t-tests showed that posttreatment scores were significantly higher than pretreatment scores in the CAMCOG subscales evaluating: attention (t[17] = –4.075; p=0.001), remote memory (t[17] = –2.153; p=0.046), calculation (t[17] = –2.961; p=0.009), language comprehension (t[17] = –2.179; p=0.44) and expression (t[17] = –3.112; p=0.006), and abstract reasoning (t[17] = –2.439; p=0.026). No significant changes were detected in terms of learning, recent memory, praxis, perception, and orientation (p>0.103).

Cognitive Test Results in the Subgroups of Subjects With No Brain Abnormalities as Assessed by CT or MRI Scanning
A similar pattern of between-group differences in CAMCOG ratings emerged when the analyses were restricted to the subjects with no signs of gross brain lesions as assessed by MRI or CT scanning. Significant differences in total CAMCOG scores before treatment were detected (ANOVA) between MDD–HF patients, nondepressed HF subjects, and healthy-controls (F[2]=125.52; p<0.001). Exploratory t-tests comparing separate CAMCOG subtests showed that in the nondepressed HF group versus controls, the subscales showing significant differences were those for learning, recent memory, language expression, and comprehension (t = –2.584, df: 33, p<0.014); the MDD–HF group showed, compared with controls, cognitive deficits in the domains of: language (comprehension and expression), attention, praxis, memory (recent and remote), calculation, abstract reasoning, and perception (t = –2.27, df: 33, p<0.030); and, compared with nondepressed HF subjects, the MDD–HF group had significantly lower scores on the CAMCOG subscales evaluating language, remote memory, praxis, calculation, abstract reasoning, and perception (t = –2.39, df: 32, p<0.023). Such an overall pattern of results would indicate that the above findings of cognitive decline in association with HF and MDD were not determined by gross brain lesions that might have been present in the subjects who did not have CT or MRI data available at the time of our study.

The evaluation of posttreatment CAMCOG differences in the subsample of 15 MDD–HF patients with available CT or MRI data showed a statistically significant increase in total CAMCOG scores (from 52.47 (SD: 10.97) to 60.53 (SD: 13.70), t[14]=4.344; p=0.001). Exploratory paired t-tests showed that posttreatment scores were significantly higher relative to pretreatment scores on the CAMCOG subscales evaluating learning (t[14]=3.640; p=0.003), remote memory (t[14] = –2.779; p=0.015), attention (t[14] = –3.154; p=0.007), calculation (t[14] = –2.827; p=0.013), abstract reasoning (t[14] = –2.582; p=0.22), and language expression (t[14]=2.256; p=0.041). There was also a trend toward higher posttreatment scores on language comprehension (p=0.082), whereas no significant changes were detected on the recent memory, perception, orientation, and praxis subscales (p>0.228).


  DISCUSSION

 
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 ABSTRACT
 INTRODUCTION
 METHOD
 RESULTS
 DISCUSSION
REFERENCES
 
Using the CAMCOG battery, we replicated the results of previous investigations, which have demonstrated the presence of significant cognitive deficits in association with the diagnosis of HF.2,22,23 Also, to the best of our knowledge, our study is the first to compare directly the cognitive performance of HF subjects subdivided according to the presence or absence of MDD and to provide empirical evidence that cognitive deficits can be significantly improved with antidepressant treatment in HF subjects suffering from comorbid MDD.

Because the CAMCOG is validated as a screening instrument, rather than a detailed neuropsychological evaluation,18 inferences about performance variation between the separate subscales of this cognitive battery have to be made with great caution. However, it is interesting to note that our MDD–HF group had a greater degree of impairment than nondepressed HF patients across several CAMCOG subscales. This pattern is consistent with the global cognitive impairment identified in previous investigations of late-life idiopathic major depression,9 which, in its most severe form, is described as depressive pseudodementia.19 Indeed, the mean (SD) CAMCOG scores of our MDD–HF sample before antidepressant treatment (52.4; SD: 10.9) fell within the range of values seen in neurodegenerative-dementia patients tested with this cognitive screening battery.24,25 However, after the 8-week treatment trial with SSRIs, there were significant changes on several CAMCOG subscales in the MDD–HF subjects, bringing their overall performance to a level comparable with that of nondepressed HF patients (61.8; SD: 14.3).24 Such improvement in cognitive performance after short-term antidepressant use reinforces the importance of a careful assessment of the presence of major depressive symptoms in patients suffering from HF and associated cognitive deficits. Our findings also suggest that, despite the microstructural brain changes that probably play a major causal role in the cognitive decline associated with HF,26 such cognitive deficits are still amenable to improvement even when MDD is present in comorbidity with the cardiac symptoms.27,28 This would be in agreement with previous suggestions that the vigorous pharmacological treatment of major depressive symptoms results in significant alleviation of concomitant cognitive deficits in disorders associated with definite brain damage.29

One question related to the use of antidepressants in elderly subjects concerns the cardiovascular (mainly arrhythmic) risks associated with these pharmacological agents.30,31 For the present study, we chose to use two drugs from the SSRI class that have been previously shown to be well tolerated in patients with cardiac disease32 and to have a consistently lower risk of inducing arrhythmic changes than do tricyclic antidepressants.30,31 Although the structured cardiological evaluation was not repeated after antidepressant treatment in our MDD–HF sample, all patients were followed by two cardiologists (JR and MW), and none of those subjects were judged to have shown a deterioration of their cardiac condition that could be attributed to antidepressant-related arrhythmic changes.

Because the Ham-D includes somatic items (mainly insomnia, loss of energy, and weight changes) that can be scored positively as a result of the symptoms of HF itself (regardless of the presence of depressive symptoms), we chose to exclude MDD–HF subjects whose were classified as mild (Ham-D scores <18). Most probably for the same reason, our nondepressed HF group showed significantly higher depression severity (Ham-D) ratings than the healthy-control subjects, despite the absence of MDD symptoms according to the SCID; this reinforces the notion that somatic features are not reliable markers for depression in general-hospital settings.33 By using the SCID,11 it was possible not only to discard the presence of previous MDD episodes in the nondepressed HF subjects, but also to exclude subjects presenting with other major psychiatric conditions. The CAMCOG testing in this nondepressed HF group revealed the presence of significant cognitive impairment relative to healthy-controls, thus indicating that even after excluding cases with comorbid MDD, cognitive deficits remain detectable and significant in HF subjects. It is unlikely that the pattern of cognitive decline in the nondepressed HF group could have been determined by undetected vascular-related macroscopic structural brain abnormalities,34 given that CAMCOG scores remained significantly lower relative to healthy-controls when the analysis was restricted to the subgroup of nondepressed HF subjects with no signs of cortical or lacunar infarcts as assessed by CT or MRI scanning. It is unlikely that the degree of cognitive impairment seen in our nondepressed HF patients could significantly diminish with further cardiovascular treatment. Although previous studies have shown that cognitive deficits associated with HF can be alleviated after treatment strategies that improve the cardiac output to the brain,35 our HF patients had already been stabilized on an optimized pharmacological treatment for HF before the study, as well as for associated clinical conditions such as arterial hypertension.36

The findings of our study must be interpreted with caution because of its several limitations, such as the relatively modest size of the HF sample investigated. This was due to our choice to include only HF subjects in functional classes II and III, as well as the use of stringent exclusion criteria regarding the presence of personal or family history of major neuropsychiatric disorders and the use of psychoactive drugs. One other limitation was the exclusion of subjects with signs of carotid obstruction, as inferred exclusively from physical examination, and we cannot exclude the possibility that our sample included subjects with mild carotid obstruction that would only be detectable by carotid Doppler ultrasonography. Another methodological issue is the fact that we did not use a double-blinded design, with cognitive evaluations performed twice both in depressed and nondepressed HF subjects by raters with no knowledge about MDD diagnosis or antidepressant use. It should also be noted that the repeated exposure of subjects to the neuropsychological tests in our study could have led to inflated posttreatment scores in the MDD–HF group due to learning, rather than reflecting improvement secondary to antidepressant treatment; however, this kind of learning effect was probably minimized by the 2-month interval between the two administrations of the cognitive tests. Finally, as a structured reevaluation of heart function was not conducted after antidepressant treatment, we cannot dismiss the possibility that the observed cognitive changes could have been due to an interaction between antidepressant effectiveness and cardiac function improvement; however, this possibility does not invalidate our observation that the introduction of antidepressant agents was a key element in improving the cognitive performance of HF patients with comorbid MDD.

The presence of depressive symptoms in association with poorer cognitive functioning is very likely to interfere with the treatment compliance of subjects with HF, as well as with their daily activities and overall quality of life. Clinicians should be encouraged to actively investigate the comorbidity with depressive symptoms and the cognitive profile of their HF patients. Our findings provide support to the proposition that an early identification of major depressive symptoms and prompt intervention with anti-depressant agents, can significantly reduce the severity of cognitive deficits associated with HF.28 In order to further strengthen this idea, our exploratory results should be confirmed in future clinical studies involving larger HF samples, using double-blind designs so as to avoid spurious effects, and including reassessments of both mental symptoms and cardiac functioning over longer periods of follow-up after the introduction of antidepressant treatment.


  ACKNOWLEDGMENTS

 
The authors thank Leandro Michelon for assistance in the clinical follow-up of subjects suffering from heart failure and comorbid major depressive disorder.

This study was supported by a grant from the Fundação de Amparo á Pesquisa do Estado de São Paulo (FAPESP-Brazil; Project 99/11562-0 and 99/04993-5).


  REFERENCES

 
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 ABSTRACT
 INTRODUCTION
 METHOD
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Zambroski CH: Qualitative analysis of living with heart failure. Heart Lung 2003; 32:32–40[CrossRef][Medline]
  2. Trojano L, Antonelli-Incalzi R, Acanfora D, et al: Cognitive impairment: a key feature of congestive heart failure in the elderly. J Neurol 2003; 250:1456–1463[CrossRef][Medline]
  3. Zuccala G, Pedone C, Cesari M, et al: The effects of cognitive impairment on mortality among hospitalized patients with heart failure. Am J Med 2003; 115:97–103[Medline]
  4. Almeida OP, Flicker L: The mind of a failing heart: a systematic review of the association between congestive heart failure and cognitive functioning. Intern Med J 2001; 31:290–295[CrossRef][Medline]
  5. Antonelli-Incalzi R, Trojano L, Acanfora D, et al: Verbal memory impairment in congestive heart failure. J Clin Exp Neuropsychol 2003; 25:14–23[Medline]
  6. Williams SA, Kasl SV, Heiat A, et al: Depression and risk of heart failure among the elderly: a prospective, community-based study. Psychosom Med 2002; 64:6–12[Abstract/Free Full Text]
  7. Thomas SA, Friedmann E, Khatta M, et al: Depression in patients with heart failure: physiologic effects, incidence, and relation to mortality. AACN Clin Issues 2003; 14:3–12[Medline]
  8. Braunstein JB, Anderson GF, Gerstenblith G, et al: Noncardiac comorbidity increases preventable hospitalizations and mortality among Medicare beneficiaries with chronic heart failure. J Am Coll Cardiol 2003; 42:1226–1233[Abstract/Free Full Text]
  9. Marvel CL, Paradiso S: Cognitive and neurological impairment in mood disorders. Psychiatr Clin North Am 2004; 27:19–36, vii-viii[CrossRef][Medline]
  10. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Washington, DC, American Psychiatric Press, Inc., 1994
  11. First MB, Opler LA, Hamilton RM, et al: Evaluation in an inpatient setting of Dtree, a computer-assisted diagnostic assessment procedure. Compr Psychiatry 1993; 34:171–175[CrossRef][Medline]
  12. Hamilton M: Rating depressive patients. J Clin Psychiatry 1980; 41:21–24[Medline]
  13. Scheltens P, Barkhof F, Valk J, et al: White-matter lesions on magnetic resonance imaging in clinically diagnosed Alzheimer’s disease: evidence for heterogeneity. Brain 1992; 115(Pt 3):735-748
  14. Almeida JR, Alves TC, Wajngarten M, et al: Late-life depression, heart failure, and frontal white-matter hyperintensity: a structural magnetic resonance imaging study. Braz J Med Biol Res 2005; 38:431–436[Medline]
  15. Longstreth WT Jr, Bernick C, Manolio TA, et al: Lacunar infarcts defined by magnetic resonance imaging of 3,660 elderly people: The Cardiovascular Health Study. Arch Neurol 1998; 55:1217–1225[Abstract/Free Full Text]
  16. Folstein MF, Robins LN, Helzer JE: The Mini-Mental State Exam. Arch Gen Psychiatry 1983; 40:812[Medline]
  17. Roth M, Tym E, Mountjoy CQ, et al: Camdex: a standardised instrument for the diagnosis of mental disorder in the elderly with special reference to the early detection of dementia. Br J Psychiatry 1986; 149:698–709[Abstract/Free Full Text]
  18. Huppert FA, Brayne C, Gill C, et al: CAMCOG: a concise neuropsychological test to assist dementia diagnosis: sociodemographic determinants in an elderly population sample. Br J Clin Psychol 1995; 34(Pt 4):529-541
  19. Lantz MS, Buchalter EN: Pseudodementia: cognitive decline caused by untreated depression may be reversed with treatment. Geriatrics 2001; 56:42–43[Medline]
  20. Stoudemire A, Hill CD, Morris R, et al: Improvement in depression-related cognitive dysfunction following ECT. J Neuropsychiatry Clin Neurosci 1995; 7:31–34[Abstract/Free Full Text]
  21. Elwood PC, Pickering J, Bayer A, et al: Vascular disease and cognitive function in older men in The Caerphilly Cohort. Age Ageing 2002; 31:43–48[Abstract/Free Full Text]
  22. Verhaegen P, Borchelt M, Smith J: Relation between cardiovascular and metabolic disease and cognition in very old age: cross-sectional and longitudinal findings from The Berlin Aging Study. Health Psychol 2003; 22:559–569[CrossRef][Medline]
  23. Zuccala G, Marzetti E, Cesari M, et al: Correlates of cognitive impairment among patients with heart failure: results of a multicenter survey. Am J Med 2005; 118:496–502[CrossRef][Medline]
  24. Lolk A, Nielsen H, Andersen K, et al: CAMCOG as a screening instrument for dementia: The Odense Study: Cambridge Cognitive Examination. Acta Psychiatr Scand 2000; 102:331–335[CrossRef][Medline]
  25. Lindeboom J, Ter Horst R, Hooyer C, et al: Some psychometric properties of the CAMCOG. Psychol Med 1993; 23:213–219[Medline]
  26. Farkas E, De Jong GI, Apro E, et al: Similar ultrastructural breakdown of cerebrocortical capillaries in Alzheimer’s disease, Parkinson’s disease, and experimental hypertension: what is the functional link? Ann N Y Acad Sci 2000; 903:72–82[Abstract/Free Full Text]
  27. Rocca P, Calvarese P, Faggiano F, et al: Citalopram versus sertraline in late-life nonmajor clinically significant depression: a 1-year follow-up clinical trial. J Clin Psychiatry 2005; 66:360–369[Medline]
  28. Doraiswamy PM, Krishnan KR, Oxman T, et al: Does antidepressant therapy improve cognition in elderly depressed patients? J Gerontol A Biol Sci Med Sci 2003; 58:M1137-1144
  29. Fann JR, Uomoto JM, Katon WJ: Cognitive improvement with treatment of depression following mild traumatic brain injury. Psychosomatics 2001; 42:48–54[Abstract/Free Full Text]
  30. Alvarez W Jr, Pickworth KK: Safety of antidepressant drugs in the patient with cardiac disease: a review of the literature. Pharmacotherapy 2003; 23:754–771[CrossRef][Medline]
  31. Roose SP, Glassman AH, Attia E, et al: Cardiovascular effects of fluoxetine in depressed patients with heart disease. Am J Psychiatry 1998; 155:660–665[Abstract/Free Full Text]
  32. Jiang W, Davidson JR: Antidepressant therapy in patients with ischemic heart disease. Am Heart J 2005; 150:871–881[CrossRef][Medline]
  33. Perlis RH, Fraguas R, Fava M, et al: Prevalence and clinical correlates of irritability in major depressive disorder: a preliminary report from The Sequenced Treatment Alternatives to Relieve Depression Study. J Clin Psychiatry 2005; 66:159–166[Medline]
  34. Pullicino PM, Hart J: Cognitive impairment in congestive heart failure? embolism vs. hypoperfusion. Neurol 2001; 57:1945–1946[Free Full Text]
  35. Almeida OP, Tamai S: Congestive heart failure and cognitive functioning amongst older adults. Arch Q Neuropsiquiatr 2001; 59:324–329
  36. Korf ES, White LR, Scheltens P, et al: Mid-life blood pressure and the risk of hippocampal atrophy: The Honolulu Asia Aging Study. Hypertension 2004; 44:29–34[Abstract/Free Full Text]




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