Cardiovascular Psychiatry and Neurology

A Systematic Review of Depression and Anxiety in Patients with Atrial Fibrillation: The Mind-Heart Link

Sat, 27 Apr 2013 13:05:19 +0000

Atrial fibrillation (AF) is the most commonly seen arrhythmia in clinical practice. At present, few studies have been conducted centering on depression and anxiety in AF patients. Our aim in this systematic review is to use the relevant literature to (1) describe the prevalence of depression and anxiety in AF patients, (2) assess the impact that depression and anxiety have on illness perception in patients with AF, (3) provide evidence to support a hypothetical connection between the pathophysiology of AF and depression and anxiety, (4) evaluate the benefit of treatment of AF on depression and anxiety, and (5) give insight on medically managing a patient with AF and concomitant depression and anxiety.

Depression and Cardiac Disease: Epidemiology, Mechanisms, and Diagnosis

Sun, 07 Apr 2013 16:59:37 +0000

In patients with cardiovascular disease (CVD), depression is common, persistent, and associated with worse health-related quality of life, recurrent cardiac events, and mortality. Both physiological and behavioral factors—including endothelial dysfunction, platelet abnormalities, inflammation, autonomic nervous system dysfunction, and reduced engagement in health-promoting activities—may link depression with adverse cardiac outcomes. Because of the potential impact of depression on quality of life and cardiac outcomes, the American Heart Association has recommended routine depression screening of all cardiac patients with the 2- and 9-item Patient Health Questionnaires. However, despite the availability of these easy-to-use screening tools and effective treatments, depression is underrecognized and undertreated in patients with CVD. In this paper, we review the literature on epidemiology, phenomenology, comorbid conditions, and risk factors for depression in cardiac disease. We outline the associations between depression and cardiac outcomes, as well as the mechanisms that may mediate these links. Finally, we discuss the evidence for and against routine depression screening in patients with CVD and make specific recommendations for when and how to assess for depression in this high-risk population.

Adult Medication-Free Schizophrenic Patients Exhibit Long-Chain Omega-3 Fatty Acid Deficiency: Implications for Cardiovascular Disease Risk

Wed, 27 Feb 2013 08:54:42 +0000

Deficiency in long-chain omega-3 (LCn − 3) fatty acids, eicosapentaenoic acid (EPA, 20:5n − 3) and docosahexaenoic acid (DHA, 22:6n − 3), has been implicated in the pathoetiology of cardiovascular disease, a primary cause of excess premature mortality in patients with schizophrenia (SZ). In the present study, we determined erythrocyte EPA + DHA levels in adult medication-free patients SZ () and age-matched healthy controls (). Erythrocyte EPA + DHA composition exhibited by SZ patients (3.5%) was significantly lower than healthy controls (4.5%, −22%, ). The majority of SZ patients (72%) exhibited EPA+DHA levels ≤4.0% compared with 37% of controls (Chi-square, ). In contrast, the omega-6 fatty acid arachidonic acid (AA, 20:4) (+9%, ) and the AA:EPA + DHA ratio (+28%, ) were significantly greater in SZ patients. Linoleic acid (18:2) was significantly lower (−12%, ) and the erythrocyte 20:3/18:2 ratio (an index of delta6-desaturase activity) was significantly elevated in SZ patients. Compared with same-gender controls, EPA + DHA composition was significantly lower in male (−19%, ) but not female (−13%, ) SZ patients, whereas the 20:3/18:2 ratio was significantly elevated in both male (+22%, ) and female (+22%, ) SZ patients. These results suggest that the majority of SZ patients exhibit low LCn − 3 fatty acid levels which may place them at increased risk for cardiovascular morbidity and mortality.

Apathy and Cognitive Test Performance in Patients Undergoing Cardiac Testing

Mon, 21 Jan 2013 15:47:42 +0000

Background. Psychiatric comorbidity is common in patients with cardiovascular disease, with the literature indicating that this population may be at risk for apathy. The current study examined the prevalence of apathy in patients with cardiovascular disease and its relation to aspects of cognitive function. Methods. 123 participants from an outpatient cardiology clinic completed a brief neuropsychological battery, a cardiac stress test, and demographic information, medical history, and depression symptomatology self-report measures. Participants also completed the Apathy Evaluation Scale to quantify apathy. Results. These subjects reported limited levels of apathy and depression. Increased depressive symptomatology, history of heart attack, and metabolic equivalents were significantly correlated with apathy (). Partial correlations adjusting for these factors revealed significant correlations between behavioral apathy and a measure of executive function and the other apathy subscale with a measure of attention. Conclusion. Findings revealed that apathy was not prevalent in this sample though associated with medical variables. Apathy was largely unrelated to cognitive function. This pattern may be a result of the mild levels of cardiovascular disease and cognitive dysfunction in the current sample. Future studies in samples with severe cardiovascular disease or neuropsychological impairment may provide insight into these associations.

Higher Cortisol Predicts Less Improvement in Verbal Memory Performance after Cardiac Rehabilitation in Patients with Coronary Artery Disease

Wed, 16 Jan 2013 09:42:11 +0000

Objective. While physical activity can improve verbal memory performance in subjects with coronary artery disease (CAD), there is large variability in response. Elevated cortisol production has been suggested to negatively affect verbal memory performance, yet cortisol concentrations have not been assessed as a predictor of response to exercise intervention in those with CAD. Methods. CAD patients participating in a one-year cardiac rehabilitation program were recruited. Memory was assessed with the California Verbal Learning Test second edition at baseline and one year. Cortisol was measured from a 20 mg, 3.0 cm hair sample collected at baseline. Results. In patients with CAD (, mean ± SD age = , 86% male), higher cortisol (hair cortisol concentrations ≥ 153.2 ng/g) significantly predicted less memory improvement (, ) when controlling for age (, ), gender (, ), maximal oxygen uptake (, ), and body mass index (, ). Conclusion. Prolonged hypothalamic pituitary adrenal axis activation may interfere with exercise-related improvements in memory in CAD.

Multiple Sclerosis and the Blood-Central Nervous System Barrier

Alan M. Palmer — Tue, 15 Jan 2013 15:30:55 +0000

The central nervous system (CNS) is isolated from the blood system by a physical barrier that contains efflux transporters and catabolic enzymes. This blood-CNS barrier (BCNSB) plays a pivotal role in the pathophysiology of multiple sclerosis (MS). It binds and anchors activated leukocytes to permit their movement across the BCNSB and into the CNS. Once there, these immune cells target particular self-epitopes and initiate a cascade of neuroinflammation, which leads to the breakdown of the BCNSB and the formation of perivascular plaques, one of the hallmarks of MS. Immunomodulatory drugs for MS are either biologics or small molecules, with only the latter having the capacity to cross the BCNSB and thus have a propensity to cause CNS side effects. However, BCNSB penetration is a desirable feature of MS drugs that have molecular targets within the CNS. These are nabiximols and dalfampridine, which target cannabinoid receptors and potassium channels, respectively. Vascular cell adhesion molecule-1, present on endothelial cells of the BCNSB, also serves as a drug discovery target since it interacts with α4-β1-integrin on leucocytes. The MS drug natalizumab, a humanized monoclonal antibody against α4-β1-integrin, blocks this interaction and thus reduces the movement of immune cells into the CNS. This paper further elaborates on the role of the BCNSB in the pathophysiology and pharmacotherapy of MS.

Cardiovascular Risk Factors Promote Brain Hypoperfusion Leading to Cognitive Decline and Dementia

Jack C. de la Torre — Mon, 03 Dec 2012 11:29:54 +0000

Heart disease is the major leading cause of death and disability in the world. Mainly affecting the elderly population, heart disease and its main outcome, cardiovascular disease, have become an important risk factor in the development of cognitive decline and Alzheimer’s disease (AD). This paper examines the evidence linking chronic brain hypoperfusion induced by a variety of cardiovascular deficits in the development of cognitive impairment preceding AD. The evidence indicates a strong association between AD and cardiovascular risk factors, including ApoE4, atrial fibrillation, thrombotic events, hypertension, hypotension, heart failure, high serum markers of inflammation, coronary artery disease, low cardiac index, and valvular pathology. In elderly people whose cerebral perfusion is already diminished by their advanced age, additional reduction of cerebral blood flow stemming from abnormalities in the heart-brain vascular loop ostensibly increases the probability of developing AD. Evidence also suggests that a neuronal energy crisis brought on by relentless brain hypoperfusion may be responsible for protein synthesis abnormalities that later result in the classic neurodegenerative lesions involving the formation of amyloid-beta plaques and neurofibrillary tangles. Insight into how cardiovascular risk factors can induce progressive cognitive impairment offers an enhanced understanding of the multifactorial pathophysiology characterizing AD and ways at preventing or managing the cardiovascular precursors of this dementia.

Are Cardiovascular Risk Factors Associated with Verbal Learning and Memory Impairment in Patients with Schizophrenia? A Cross-Sectional Study

Mon, 19 Nov 2012 16:31:18 +0000

Objective. The aim of this study is to assess the relationships of cardiovascular risk factors with verbal learning and memory in patients with schizophrenia. Methods and Design. cross-sectional study. Inclusion Criteria. Diagnosis of schizophrenia according to the DSM-IV-TR criteria. Data Collection. Sociodemographic information, clinical characteristics, anthropometric measurements, blood tests, and episodic memory using the California Verbal Learning Test (CVLT). Analysis. A multivariate analysis using multiple linear regressions was performed to determine variables that are potentially associated with verbal learning and memory. Results. One hundred and sixty-eight outpatients participated in our study. An association was found between the metabolic syndrome (MetS) and memory impairment on measures of verbal learning, and short- and long-term memory. Among the different components of MeTS, hypertriglycerides, abdominal obesity, and low HDL cholesterol were the only factors associated with memory impairment. Alcohol dependence or abuse was associated with a higher rate of forgetting. Conclusion. Our findings suggest that MetS and alcohol use may be linked with memory impairment in schizophrenia. These findings provide important insights into the interdependencies of cardiovascular risk factors and cognitive disorders and support novel strategies for treating and preventing cognitive disorders in patients with schizophrenia.

Cardiac Responses during Picture Viewing in Young Male Patients with Schizophrenia

Sat, 10 Nov 2012 18:16:33 +0000

Previous research investigating the emotion recognition ability in patients with schizophrenia has mainly focused on the recognition of facial expressions. To broaden our understanding of emotional processes in patients with schizophrenia, this study aimed to investigate whether these patients experience and process other emotionally evocative stimuli differently from healthy participants. To investigate this, we measured the cardiac and subjective responses of 33 male patients (9 with and 24 without antipsychotic medication) and 40 male control subjects to emotion-eliciting pictures. Cardiac responses were chosen as an outcome measure because previous research has indicated that these are linked with attentional and emotional processes and provide a more objective measure than self-report measures alone. The differences in cardiac responses between patients and controls were limited to medicated patients: only the medicated patients showed significantly decreased cardiac orienting responses compared with control subjects, regardless of picture contents. These results indicate that medicated patients directed less attention towards emotion-eliciting pictures than controls. Decreased attentional resources while processing emotional evocative stimuli could lead to incorrect appraisals of the environment and may have detrimental emotional and social consequences, contributing to chronic stress levels and an increased risk for cardiovascular disease.

Smoking Cessation Intervention in a Cardiovascular Hospital Based Clinical Setting

Sun, 14 Oct 2012 18:54:41 +0000

Introduction. Smoking is a leading cause of morbidity and mortality globally and it is a significant modifiable risk factor for cardiovascular disease (CVD) and other chronic diseases. Efforts to encourage and support smokers to quit are critical to prevent premature smoking-associated morbidity and mortality. Hospital settings are seldom equipped to help patients to quit smoking thus missing out a valuable opportunity to support patients at risk of smoking complications. We report the impact of a smoking cessation clinic we have established in a tertiary care hospital setting to serve patients with CVD. Methods. Patients received behavioural and pharmacological treatments and were followed up for a minimum of 6 months (mean 541 days, SD 197 days). The main study outcome is ≥50% reduction in number of cigarettes smoked at followup. Results. One hundred and eighty-six patients completed ≥6 months followup. More than half of the patients (52.7%) achieved ≥50% smoking reduction at follow up. Establishment of a plan to quit smoking and use of nicotine replacement therapy (NRT) were significantly associated with smoking reduction at followup. Conclusions. A hospital-based smoking cessation clinic is a beneficial intervention to bring about smoking reduction in approximately half of the patients.

Takotsubo or Stress Cardiomyopathy

J. P. Bounhoure — Fri, 28 Sep 2012 11:45:29 +0000

Many case reports have been published of reversible left ventricular dysfunction precipitated by sudden emotional stress. We have evaluated 10 women hospitalized for acute chest pain and dyspnea, mimicking an acute coronary syndrome, after a severe emotional trigger. Those patients, postmenopausal women, presented ST segment alterations on the EKG, minor elevations of cardiac enzymes, and biomarkers levels. At the coronarography there was not coronary thrombosis or severe stenosis, but the ventriculography showed wall motion abnormalities involving the left ventricular apex and midventricle, in the absence of significant obstructive coronary disease. The course was benign without complication, with a full recovery of left ventricular function in some weeks. These observations, like other reports, demonstrate the impact of emotional stress on left ventricular function and the risk of cardiovascular disease. The cause of this cardiomyopathy is still unknown, and several mechanisms have been proposed: catecholamine myocardial damage, microvascular spasm, or neural mediated myocardial stunning.

Association of Ultrasonographic Parameters with Subclinical White-Matter Hyperintensities in Hypertensive Patients

Wed, 26 Sep 2012 13:29:17 +0000

Background and Purpose. Cerebral white matter hyperintensities (WMHs) are regarded as typical MRI expressions of small-vessel disease (SVD) and are common in hypertensive patients. Hypertension induces pathologic changes in macrocirculation and in microcirculation. Changes in microcirculation may lead to SVD of brain and consequently to hypertensive end-organ damage. This damage is regarded the result of interactions between the macrovascular and microvascular levels. We sought to investigate the association of cerebral WMHs with ultrasonographic parameters of cerebral macrocirculation evaluated by carotid duplex ultrasound (CDU) and transcranial doppler (TCD). Subjects and Methods. The study was prospective, cross-sectional and consecutive and included hypertensive patients with brain MRI with WMHs. Patients underwent CDU and TCD. The clinical variables recorded were demographic characteristics (age, gender, race) and vascular risk factors (hypertension, diabetic mellitus, hypercholesterolemia, current smoking, and body mass index). Excluded from the study were patients with history of clinical stroke (including lacunar stroke and hemorrhagic) or transient ischemic attack (either hemispheric or ocular), hemodynamically significant (>50%) extra- or intracranial stenosis, potential sources of cardioembolism, and absent transtemporal windows. WMHs were quantified with the use of a semiquantitative visual rating method. Ultrasound parameters investigated were (1) common carotid artery (CCA) diameter and intima-media thickness, (2) blood flow velocity in the CCA and internal carotid artery (ICA), and (3) blood flow velocity and pulsatility index of middle cerebral artery (MCA). Results. A total of 52 patients fulfilled the study inclusion criteria (mean age years, 54% men, median WMH-score: 20). The only two ultrasound parameters that were independently associated with WMH score in multivariate linear regression models adjusting for demographic characteristics and vascular risk factors were increased mean common carotid artery (CCA) diameter (, , , %) and increased middle cerebral artery pulsatility index (MCA-PI; , , , %). Among all ultrasound parameters the highest AUC (areas under the receiver operating characteristic curve) were documented for MCA-PI (, 95% CI = 0.68−0.95, ) and mean CCA diameter (, 95% CI = 0.67−0.92, ). Conclusions. Our study showed that in hypertensive individuals with brain SVD the extent of structural changes in cerebral microcirculation as reflected by WMHs burden is associated with the following ultrasound parameters of cerebral macrocirculation: CCA diameter and MCA-PI.

The Clinical Features and Emotional Stressors in Korean Patients with Tako-Tsubo Cardiomyopathy

Bong Gun Song, Ju Hyeon Oh, Yong Hwan Park, Gu Hyun Kang, and Woo Jung Chun — Wed, 12 Sep 2012 13:20:13 +0000

Background. Tako-tsubo cardiomyopathy (TTC) is typically triggered by an acute emotional or physical stress events. Aim of this study was to investigate the impact of emotional stressors on clinical features, laboratory parameters, electrocardiographic and echocardiographic findings in patients with TTC. Methods. Of 103 patients enrolled from the TTC registry database, fifteen patients had emotional triggers (E group), and 88 patients had physical triggers or no triggers (other group). Results. Most clinical presentations and in-hospital courses were similar between the groups. However, E group had higher prevalence of chest pain (87 versus 42 %, 𝑃=0.001), palpitation (27 versus 6%, 𝑃=0.008), whereas other group had higher prevalence of cardiogenic shock (35 versus 7%, 𝑃=0.027). E group had significantly higher corrected QT intervals (median, 477.5 versus 438 ms, 𝑃=0.001), and left ventricular ejection fraction (LVEF) (mean, 45.7 versus 39.6%, 𝑃=0.001), but lower hs-CRP (median, 0.1 versus 3.3 mg/L, 𝑃=0.001), CK-MB (median, 5.5 versus 11.9 ng/mL, 𝑃=0.047), troponin-I (median, 1.0 versus 3.2 ng/mL, 𝑃=0.011), and NT-proBNP levels (median, 2145 versus 4939 pg/mL, 𝑃=0.020). Other group required more frequent hemodynamic support and had significantly longer intensive care unit (median, 3 versus 1 days, 𝑃=0.005) and in-hospital (median, 17 versus 3 days, 𝑃=0.001) durations. Conclusion. The clinical features of TTC are different between groups with and without preceding emotional stressors. The TTC group with preceding emotional stressors was more likely to have preserved cardiovascular reserve and lesser likely to require hemodynamic support than other group although the entire prognosis of TTC is excellent regardless of triggering stressors.

Reduced Heart Rate Recovery Is Associated with Poorer Cognitive Function in Older Adults with Cardiovascular Disease

Tue, 04 Sep 2012 14:21:19 +0000

Cardiovascular disease (CVD) in older adults has been associated with varying degrees of cognitive dysfunction. Several mechanisms may explain this association, including impaired cardiovascular reactivity to autonomic nervous system (ANS) signaling. Reduced heart rate recovery following a stress test may be considered an indication of impaired ANS function (i.e., reduced parasympathetic activity). Participants were 47 older adults (53–83 years) who underwent a treadmill stress test and were administered a comprehensive neuropsychological battery upon entry to phase II cardiac rehabilitation. Reduced parasympathetic activity was associated with impaired cognitive performance on a measure of global cognitive function and on tasks of speeded executive function and confrontation naming. These relationships suggest that changes in autonomic function may be mechanistically related to the impaired cognitive function prevalent in CVD patients.

Stroke and Disorders of Consciousness

Mon, 03 Sep 2012 11:48:03 +0000

Objectives. To determine the severity of stroke and mortality in relation to the type of disturbance of consciousness and outcome of patients with disorders of consciousness. Patients and Methods. We retrospectively analyzed 201 patients. Assessment of disorders of consciousness is performed by Glasgow Coma Scale (Teasdale and Jennet, 1974) and the Diagnostic and Statistical Manual of Mental Disorders (Anonymous, 2000). The severity of stroke was determined by National Institutes of Health Stroke Scale (Lyden et al., 2011). Results. Fifty-four patients had disorders of consciousness (26.9%). Patients with disorders of consciousness on admission (𝑃<0.001) and discharge (𝑃=0.003) had a more severe stroke than patients without disturbances of consciousness. Mortality was significantly higher in patients with disorders of consciousness (𝑃=0.0001), and there was no difference in mortality in relation to the type of disturbance of consciousness. There is no statistically significant effect of specific predictors of survival in patients with disorders of consciousness. Conclusion. Patients with disorders of consciousness have a more severe stroke and higher mortality. There is no difference in mortality and severity of stroke between patients with quantitative and qualitative disorders of consciousness. There is no statistically significant effect of specific predictors of survival in patients with disorders of consciousness.

Changes in Heart Rate Variability of Depressed Patients after Electroconvulsive Therapy

Mon, 27 Aug 2012 10:44:14 +0000

Objective. As few, small studies have examined the impact of electroconvulsive therapy (ECT) upon the heart rate variability of patients with major depressive disorder (MDD), we sought to confirm whether ECT-associated improvement in depressive symptoms would be associated with increases in HRV linear and nonlinear parameters. Methods. After providing consent, depressed study participants (𝑛=21) completed the Beck Depression Index (BDI), and 15-minute Holter monitor recordings, prior to their 1st and 6th ECT treatments. Holter recordings were analyzed for certain HRV indices: root mean square of successive differences (RMSSD), low-frequency component (LF)/high-frequency component (HF) and short-(SD1) versus long-term (SD2) HRV ratios. Results. There were no significant differences in the HRV indices of RMSDD, LF/HF, and SD1/SD2 between the patients who responded, and those who did not, to ECT. Conclusion. In the short term, there appear to be no significant improvement in HRV in ECT-treated patients whose depressive symptoms respond versus those who do not. Future studies will reveal whether diminished depressive symptoms with ECT are reliably associated with improved sympathetic/parasympathetic balance over the long-term, and whether acute changes in sympathetic/parasympathetic balance predict improved mental- and cardiac-related outcomes.

Neurodegenerative Shielding by Curcumin and Its Derivatives on Brain Lesions Induced by 6-OHDA Model of Parkinson's Disease in Albino Wistar Rats

Wed, 15 Aug 2012 10:14:40 +0000

Study was undertaken to evaluate the neurodegenerative defending potential of curcumin (CUR), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) on 6-hydroxydopamine-(6-OHDA) induced Parkinsonism model in rats. Curcuminoids were administered (60 mg/kg, body weight, per oral) for three weeks followed by unilateral injection of 6-OHDA on 22nd day (10 μg/2 μL) into the right striatum leading to extensive loss of dopaminergic cells. The behavioral observations, biochemical markers, quantification of dopamine (DA), DOPAC, and HVA followed by dopamine (D2) receptor binding assay and tyrosine hydroxylase (TH, using immunohistochemistry) were evaluated using HPLC after three weeks of lesion. Pretreated animals showed significant protection against neuronal degeneration compared to lesion animals by normalizing the deranged levels of biomarkers and showed the potency in the order CUR > DMC > BDMC. The same order of effectiveness was observed in D2 receptors binding assay and TH immunohistochemistry study. We conclude that curcuminoids appear to shield progressive neuronal degeneration from increased oxidative attack in 6-OHDA-lesioned rats through its free radical scavenging mechanism, and DA, DOPAC, and HVA enhancing capabilities in the sequence of efficacy CUR > DMC > BDMC. Further, curcuminoids may have potential utility in treatment of many more oxidative stress-induced neurodegenerative disorders.

Ways of Coping and Biomarkers of an Increased Atherothrombotic Cardiovascular Disease Risk in Elderly Individuals

Tue, 17 Jul 2012 09:14:23 +0000

Objective. To investigate the relationship between coping and atherothrombotic biomarkers of an increased cardiovascular disease (CVD) risk in the elderly. Methods. We studied 136 elderly caregiving and noncaregiving men and women who completed the Ways of Coping Checklist to assess problem-focused coping, seeking social support (SSS), blamed self, wishful thinking, and avoidance coping. They had circulating levels of 12 biomarkers measured. We also probed for potential mediator and moderator variables (chronic stress, affect, health behavior, autonomic activity) for the relation between coping and biomarkers. Results. After controlling for demographic and CVD risk factors, greater use of SSS was associated with elevated levels of serum amyloid A (𝑃=0.001), C-reactive protein (CRP) (𝑃=0.002), vascular cellular adhesion molecule (VCAM)-1 (𝑃=0.021), and D-dimer (𝑃=0.032). There were several moderator effects. For instance, greater use of SSS was associated with elevated VCAM-1 (𝑃<0.001) and CRP (𝑃=0.001) levels in subjects with low levels of perceived social support and positive affect, respectively. The other coping styles were not significantly associated with any biomarker. Conclusions. Greater use of SSS might compromise cardiovascular health through atherothrombotic mechanisms, including elevated inflammation (i.e., serum amyloid A, CRP, VCAM-1) and coagulation (i.e., D-dimer) activity. Moderating variables need to be considered in this relationship.

Sleep Apnea and Cognitive Function in Heart Failure

Thu, 14 Jun 2012 13:48:39 +0000

Background. Prior research indicates that heart failure (HF) patients exhibit significant cognitive deficits on neuropsychological testing. Sleep apnea is associated with both HF and reduced cognitive function, but the combined impact of these conditions on cognitive function is unknown. Methods. In the current study, 172 older adults with a dual diagnosis of HF and sleep apnea or HF alone completed a battery of cognitive tests measuring attention, executive functioning, and memory. Results. Relative to patients with HF alone, persons with both HF and sleep apnea performed worse on measures of attention after adjusting for demographic and medical variables. Conclusions. The current findings suggest that HF patients with comorbid sleep apnea may be at greater risk for cognitive impairment relative to HF patient without such history. Further work is needed to clarify mechanisms for these findings and to determine whether the interactive effects on cognitive function lead to poorer patient outcomes.

Elevated Serum C-Reactive Protein Relates to Increased Cerebral Myoinositol Levels in Middle-Aged Adults

Wed, 22 Feb 2012 15:02:33 +0000

C-reactive protein (CRP), a systemic marker of inflammation, is a risk factor for late life cognitive impairment and dementia, yet the mechanisms that link elevated CRP to cognitive decline are not fully understood. In this study we examined the relationship between CRP and markers of neuronal integrity and cerebral metabolism in middle-aged adults with intact cognitive function, using proton magnetic resonance spectrocospy. We hypothesized that increased levels of circulating CRP would correlate with changes in brain metabolites indicative of early brain vulnerability. Thirty-six individuals, aged 40 to 60, underwent neuropsychological assessment, a blood draw for CRP quantification, and 1H MRS examining N-acetyl-aspartate, myo-inositol, creatine, choline, and glutamate concentrations in occipito-parietal grey matter. Independent of age, sex and education, serum CRP was significantly related to higher cerebral myo-inositol/creatine ratio (𝐹(4,31)=4.74,𝑃=0.004), a relationship which remained unchanged after adjustment for cardiovascular risk (𝐹(5,30)=4.356, CRP β = 0.322, 𝑃=0.045). Because these biomarkers are detectable in midlife they may serve as useful indicators of brain vulnerability during the preclinical period when mitigating intervention is still possible.

Depression, Strokes and Dementia: New Biological Insights into an Unfortunate Pathway

Antoine M. Hakim — Thu, 15 Dec 2011 13:47:37 +0000

The literature emphasizes the risk of depression after a stroke. Less well known is the fact that depression may be as big a risk factor for strokes as hypertension, particularly in the older age group. This article reviews the risk for stroke and cognitive impairment consequent to depression, and describes the cardiovascular and immunological mechanisms that would appear to link depression to its cerebrovascular consequences. As well, the article refers to the brain imaging signatures that may allow prediction of impending brain injury. Finally, some questions that might be explored by future research are suggested, and some practical means to identify and help those at risk for the development of depression-associated vascular disease of the brain are suggested.

Depression Is Associated with Cognitive Dysfunction in Older Adults with Heart Failure

Tue, 13 Dec 2011 08:49:24 +0000

Persons with heart failure (HF) frequently exhibit cognitive impairment with deficits in attention and memory. Depression is common in HF though its possible contribution to cognitive impairment is unknown. Cognitive dysfunction and depression may share common mechanisms in HF, as both are associated with similar abnormalities on neuroimaging. A total of 116 participants with HF (68.53±9.30 years) completed a neuropsychological battery and self-report measures of depression. Regression models showed depression incrementally and independently predicted test performance in all cognitive domains. Follow-up partial correlations revealed that greater depressive symptoms were associated with poorer performance on tests of attention, executive function, psychomotor speed, and language. These results indicate that depressive symptoms are associated with poorer cognitive performance in HF though further work is needed to clarify mechanisms for this association and possible cognitive benefits of treating depression in persons with HF.

Validation of the Turkish Version of the Problem Areas in Diabetes Scale

Tue, 13 Dec 2011 08:48:27 +0000

The Problem Areas in Diabetes (PAID) scale is a widely used self-report measure that can facilitate detection of diabetes-specific emotional distress in clinical practice. The aim of this study was to assess the factor structure and validity of the Turkish version of the PAID. A validation study was conducted among 154 patients with insulin-naïve type 2 diabetes. Participants completed the PAID, Centre for Epidemiological Studies Depression Scale (CES-D), Insulin Treatment Appraisal Scale (ITAS), and World Health Organization-Five Well-Being Index (WHO-5) questionnaires. Exploratory factor analyses yielded a 2-factor structure, identifying a 15-item “diabetes distress” factor and a 5-item “support-related issues” factor. The total PAID-score and the two dimensions were associated with higher levels of depression and poor emotional well-being. In the present study, the Turkish version of the PAID had satisfactory psychometric properties, however, the factorial structure was found to differ from factor solutions from other countries.

Diabetic Peripheral Microvascular Complications: Relationship to Cognitive Function

Lorraine Ba-Tin, Paul Strike, and Naji Tabet — Thu, 17 Nov 2011 17:47:23 +0000

Peripheral microvascular complications in diabetes are associated with concurrent cerebrovascular disease. As detailed cognitive assessment is not routinely carried out among diabetic patients, the aim was to establish whether the presence of clinical “peripheral” microvascular disease can identify a subgroup of patients with early evidence of cognitive impairment. Detailed psychometric assessment was performed in 23 diabetic patients with no microvascular complications (Group D), 27 diabetic patients with at least one microvascular complication: retinopathy, neuropathy, and/or nephropathy (Group DC), and 25 healthy controls (Group H). Groups D and DC participants had significantly lower scores on reaction time (𝑃=0.003 and 0.0001, resp.) compared to controls. Similarly, groups D and DC participants had significantly lower scores on rapid processing of visual information (𝑃=0.034 and 0.001, resp.) compared to controls. In contrast, there was no significant difference between Groups D and DC on any of the cognitive areas examined. The results show that diabetes, in general, is associated with cognitive dysfunction, but the additional presence of peripheral microvascular disease does not add to cognitive decline. The study, however, indirectly supports the notion that the aetiology of cognitive impairment in diabetes may not be restricted to vascular pathology.

Symptoms of Anxiety and Depression Are Correlates of Angina Pectoris by Recent History and an Ischemia-Positive Treadmill Test in Patients with Documented Coronary Artery Disease in the Pimi Study

Thu, 17 Nov 2011 16:05:19 +0000

Objective. We tested the association of specific psychological characteristics in patients having stable coronary disease with the reporting of anginal symptoms during daily activities, and positive exercise testing. Methods. One hundred and ninety-six patients with documented CAD enrolled in the Psychophysiological Investigations of Myocardial Ischemia (PIMI) Study completed an anginal history questionnaire and a battery of psychometric tests. They also underwent standardized exercise treadmill tests. Results. Patients with a recent history of angina were more likely to be female, and had higher Beck Depression (𝑃=.002), State Anxiety (𝑃=.001), Trait Anxiety (𝑃=.03), Harm Avoidance (𝑃=.04) and Muscle Tension (𝑃=.004) scores than patients who had no recent history of angina. Along with several treadmill variables indicating more severe disease state and reduced exercise tolerance, patients who developed angina on a positive treadmill test also displayed higher scores on the Beck Depression Inventory (𝑃=.003) and State Anxiety (𝑃=.004) scales. Conclusions. Several psychological characteristics, and most notably anxiety and depression, are strong correlates of recent angina and angina in the presence of ischemia provoked by treadmill testing.

Blood-Brain Barrier Breakdown and Blood-Brain Communication in Neurological and Psychiatric Diseases

Alon Friedman and Daniela Kaufer — Wed, 06 Jul 2011 09:36:42 +0000

Intercellular Interactomics of Human Brain Endothelial Cells and Th17 Lymphocytes: A Novel Strategy for Identifying Therapeutic Targets of CNS Inflammation

Arsalan S. Haqqani and Danica B. Stanimirovic — Mon, 13 Jun 2011 10:42:58 +0000

Leukocyte infiltration across an activated brain endothelium contributes to the neuroinflammation seen in many neurological disorders. Recent evidence shows that IL-17-producing T-lymphocytes (e.g., Th17 cells) possess brain-homing capability and contribute to the pathogenesis of multiple sclerosis and cerebral ischemia. The leukocyte transmigration across the endothelium is a highly regulated, multistep process involving intercellular communications and interactions between the leukocytes and endothelial cells. The molecules involved in the process are attractive therapeutic targets for inhibiting leukocyte brain migration. We hypothesized and have been successful in demonstrating that molecules of potential therapeutic significance involved in Th17-brain endothelial cell (BEC) communications and interactions can be discovered through the combination of advanced membrane/submembrane proteomic and interactomic methods. We describe elements of this strategy and preliminary results obtained in method and approach development. The Th17-BEC interaction network provides new insights into the complexity of the transmigration process mediated by well-organized, subcellularly localized molecular interactions. These molecules and interactions are potential diagnostic, therapeutic, or theranostic targets for treatment of neurological conditions accompanied or caused by leukocyte infiltration.

The Blood-Brain Barrier and Microvascular Water Exchange in Alzheimer's Disease

Valerie C. Anderson, David P. Lenar, Joseph F. Quinn, and William D. Rooney — Wed, 04 May 2011 17:37:48 +0000

Alzheimer's disease (AD) is the most common form of dementia in the elderly. Although traditionally considered a disease of neurofibrillary tangles and amyloid plaques, structural and functional changes in the microvessels may contribute directly to the pathogenesis of the disease. Since vascular dysfunction often precedes cognitive impairment, understanding the role of the blood-brain barrier (BBB) in AD may be key to rational treatment of the disease. We propose that water regulation, a critical function of the BBB, is disturbed in AD and results in abnormal permeability and rates of water exchange across the vessel walls. In this paper, we describe some of the pathological events that may disturb microvascular water exchange in AD and examine the potential of a relatively new imaging technique, dynamic contrast-enhanced MRI, to quantify water exchange on a cellular level and thus serve as a probe of BBB integrity in AD.

Case Series of Post-Thrombolysis Patients Undergoing Hemicraniectomy for Malignant Anterior Circulation Ischaemic Stroke

A. Williams, M. Sittampalam, N. Barua, and A. Mohd Nor — Mon, 18 Apr 2011 14:23:59 +0000

While ischaemic stroke remains a leading cause of death and disability, there have been recent advancements in treatment modalities including thrombolysis and decompressive hemicraniectomy. A retrospective review of patients treated in our NHS teaching hospital, in Plymouth (UK), over a 2 year period identified 17 thrombolysed patients, of whom two had undergone subsequent decompressive hemicraniectomy. These were non-dominant hemisphere strokes in young patients, aged 51 and 57. Initial NIHSS scores were 16 and 17, and they received thrombolysis at 2 hrs 42 min and 5 hrs 10 min post onset of symptoms respectively. CT imaging demonstrated cerebral swelling with significant midline shift in both cases, and decompressive hemicraniectomy was undertaken at 29 hrs 8 min and 27 hrs 30 min post-thrombolysis. We found no significant intra-operative complications attributable to prior use of thrombolytics. Both patients have had acceptable psychological and physical outcomes, with Barthel Index scores of 40 and 25, and MMSE scores of 29/30 and 27/30. We conclude that the use of thrombolytic therapy does not contra-indicate subsequent decompressive hemicraniectomy in well selected patients with non-dominant hemisphere strokes. More research in this field is required to elucidate factors which would facilitate recognition of stroke patients who will benefit most from aggressive medical and neurosurgical intervention.

The Etiological Role of Blood-Brain Barrier Dysfunction in Seizure Disorders

Wed, 30 Mar 2011 13:27:19 +0000

A wind of change characterizes epilepsy research efforts. The traditional approach, based on a neurocentric view of seizure generation, promoted understanding of the neuronal mechanisms of seizures; this resulted in the development of potent anti-epileptic drugs (AEDs). The fact that a significant number of individuals with epilepsy still fail to respond to available AEDs restates the need for an alternative approach. Blood-brain barrier (BBB) dysfunction is an important etiological player in seizure disorders, and combination therapies utilizing an AED in conjunction with a “cerebrovascular” drug could be used to control seizures more effectively than AED therapy alone. The fact that the BBB plays an etiologic role in other neurological diseases will be discussed in the context of a more “holistic” approach to the patient with epilepsy, where comorbidity variables are also encompassed by drug therapy.