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Introduction: Cigarette smoking is associated with increased cerebrovascular disease risk and reduced cognitive performance, particularly in domains sensitive to vascular insults, such as executive function and processing speed. Short-term blood pressure variability (BPV) is associated with cognitive decline among older adults with and without hypertension (HTN) and BPV is significantly greater among smokers than non-smokers. However, it is unknown if greater short-term BPV contributes to lower cognitive performance in smokers. We hypothesized that greater beat-to-beat BPV would be associated with lower cognitive performance in smokers and that this relation would be independent of mean blood pressure (BP). Methods: Twenty-three smokers (3 current/20 former; age 69 ± 9; pack-years 33 ± 17; systolic BP (SBP) 133 ± 18; diastolic BP (DBP) 71 ± 8; anti-HTN medication use 16Y/7N)), without chronic obstructive pulmonary disease, completed measurements of beat-to beat BPV by 10 minutes of finger plethysmography and electrocardiography, and neuropsychological testing. Age-adjusted neuropsychological test t-scores were grouped into four cognitive domains (executive function, processing speed, language and memory recall). Results: Greater systolic BPV was associated with lower cognitive performance in the executive function (r=-0.59, p Conclusion: These data suggest that greater beat-to-beat BP variability may contribute to lower cognitive performance in smokers and that this relation is independent of mean SBP.

In this chapter, we focus on the neuropsychological evaluation of patients with chronic obstructive pulmonary disease (COPD), a common adult pulmonary disorder characterized by restrictive airflow and respiratory distress. First, we will review the epidemiology and diagnostic criteria of COPD and of the most common medical comorbidities. Next, we will review the literature of cognition in patients with COPD and identify the most consistent neuropsychological deficits in the population. Multi­disciplinary rehabilitation is commonly prescribed for COPD patients. We will discuss the role of the neuropsychologist within the team. Finally, to more clearly illustrate the neuropsychological evaluation in patients with COPD, we will discuss a fictional case from our center with details regarding frequent referral questions, special considerations for the clinical interview, selection of cognitive tests, interpretation of tests, and final recommendations for the patient and/or the interdisciplinary rehabilitation team.

Background: Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality. Present-day diagnostic criteria are largely based solely on spirometric criteria. Accumulating evidence has identified a substantial number of individuals without spirometric evidence of COPD who suffer from respiratory symptoms and/or increased morbidity and mortality. There is a clear need for an expanded definition of COPD that is linked to physiologic, structural (computed tomography [CT]) and clinical evidence of disease. Using data from the COPD Genetic Epidemiology study (COPDGene®), we hypothesized that an integrated approach that includes environmental exposure, clinical symptoms, chest CT imaging and spirometry better defines disease and captures the likelihood of progression of respiratory obstruction and mortality. Methods: Four key disease characteristics – environmental exposure (cigarette smoking), clinical symptoms (dyspnea and/or chronic bronchitis), chest CT imaging abnormalities (emphysema, gas trapping and/or airway wall thickening), and abnormal spirometry – were evaluated in a group of 8784 current and former smokers who were participants in COPDGene® Phase 1. Using these 4 disease characteristics, 8 categories of participants were identified and evaluated for odds of spirometric disease progression (FEV1 > 350 ml loss over 5 years), and the hazard ratio for all-cause mortality was examined. Results: Using smokers without symptoms, CT imaging abnormalities or airflow obstruction as the reference population, individuals were classified as Possible COPD, Probable COPD and Definite COPD. Current Global initiative for obstructive Lung Disease (GOLD) criteria would diagnose 4062 (46%) of the 8784 study participants with COPD. The proposed COPDGene® 2019 diagnostic criteria would add an additional 3144 participants. Under the new criteria, 82% of the 8784 study participants would be diagnosed with Possible, Probable or Definite COPD. These COPD groups showed increased risk of disease progression and mortality. Mortality increased in patients as the number of their COPD characteristics increased, with a maximum hazard ratio for all cause-mortality of 5.18 (95% confidence interval [CI]: 4.15–6.48) in those with all 4 disease characteristics. Conclusions: A substantial portion of smokers with respiratory symptoms and imaging abnormalities do not manifest spirometric obstruction as defined by population normals. These individuals are at significant risk of death and spirometric disease progression. We propose to redefine the diagnosis of COPD through an integrated approach using environmental exposure, clinical symptoms, CT imaging and spirometric criteria. These expanded criteria offer the potential to stimulate both current and future interventions that could slow or halt disease progression in patients before disability or irreversible lung structural changes develop.

Low socioeconomic status has been associated with chronic obstructive pulmonary disease (COPD) but little is known about its impact on disease progression. We assessed the association of income to symptoms, pulmonary disease severity and progression in smokers with and without COPD. The COPDGene cohort of 4826 smokers who reported annual income in phase 2 was analysed. Those who reported annual income, Income is a factor in predicting pulmonary disease progression in smokers with and without COPD; those with lower income experience faster progression and worse symptoms http://ow.ly/1SSe30lU1cX

OBJECTIVE: Younger persons with COPD report worse health-related quality of life (HRQL) than do older individuals. The factors explaining these differences remain unclear. The objective of this article was to explore factors associated with age-related differences in HRQL in COPD. METHODS: Cross-sectional analysis of participants with COPD, any Global Initiative for Chronic Obstructive Lung Disease grade of airflow limitation, and ≥ 50 years old in two cohorts: the Genetic Epidemiology of COPD (COPDGene) study and the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS). We compared St. George's Respiratory Questionnaire (SGRQ) scores by age group: middle-aged (age, 50-64) vs older (age, 65-80) adults. We used multivariate linear modeling to test associations of age with HRQL, adjusting for demographic and clinical characteristics and comorbidities. RESULTS: Among 4,097 participants in the COPDGene study (2,170 middle-aged and 1,927 older adults) SGRQ total scores were higher (worse) among middle-aged (mean difference, -4.2 points; 95% CI, -5.7 to -2.6; P < .001) than older adults. Age had a statistically significant interaction with dyspnea (P < .001). Greater dyspnea severity (modified Medical Research Council ≥ 2, compared with 0-1) had a stronger association with SGRQ score among middle-aged (β, 24.6; 95% CI, 23.2-25.9) than older-adult (β, 21.0; 95% CI, 19.6-22.3) participants. In analyses using SGRQ as outcome in 1,522 participants in SPIROMICS (598 middle-aged and 924 older adults), we found similar associations, confirming that for the same severity of dyspnea there is a stronger association with HRQL among younger individuals. CONCLUSIONS: Age-related differences in HRQL may be explained by a higher impact of dyspnea among younger subjects with COPD. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00608764 and No.: NCT01969344; URL: www.clinicaltrials.gov.

Decreased exercise capacity in chronic obstructive pulmonary disease (COPD) is incompletely explained by pulmonary pathologic and physiologic abnormalities. We evaluated the extent to which right ventricular diastolic function (RVDF) is associated with exercise capacity in COPD.Fifty-one patients with COPD were evaluated by echocardiography, spirometry, and the 6 min walk test (6MWT). RVDF was assessed using 4 echocardiographic parameters: 1) the ratio of tricuspid valve (TV) early (E) and late (A) inflow velocities (TV E/A) 2) TV early tissue Doppler velocity (TV e') 3) TV deceleration time (DT) and 4) the ratio of TV E and e' velocities (TV E/e'). Multiple linear regression was used to examine the extent to which these parameters were associated with 6MWT distance. All models adjusted for age, sex, post-bronchodilator FEV1/FVC, resting heart rate, and use of supplemental O2 during 6MWT. A regression model was calculated for each of the 4 markers of RVDF.Forty-seven percent of the sample had GOLD stage III or IV COPD. All 51 subjects had preserved left ventricular ejection fraction (LVEF, mean = 71.7%, SD = 7.8%). A higher TV E/A ratio was associated with increased 6MWT distance (p = 0.001). TV e', TV DT and TV E/e' did not have a statistically significant association with 6MWT distance in regression models.In a cohort with moderate to severe COPD and normal LVEF, TV E/A was associated with 6MWT distance after adjusting for relevant demographic and medical covariates. RV diastolic dysfunction may independently contribute to exercise intolerance in COPD.

Background: Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are two of the most prevalent respiratory disorders in adults and are both independently associated with increased cardiovascular disease (CVD) risk. The coexistence of OSA in individuals with COPD is termed “overlap syndrome” and occurs in up to 65% of all COPD patients. Individuals with overlap syndrome have more frequent COPD exacerbations, poorer quality of life and increased CVD morbidity than patients with either COPD or OSA alone. COPD and OSA are both independently associated with increased carotid artery stiffness, a predictor of CVD events. However, the interaction of COPD and OSA on carotid artery stiffness remains unknown. We hypothesized that a) carotid artery stiffness would be greater in patients with overlap syndrome than COPD patients without OSA and non-COPD controls and b) overlap syndrome patients that reported using continuous positive airway pressure (CPAP) would have lower carotid artery stiffness than overlap patients not using a CPAP. Methods: Ninety-nine former smokers (n=62 with COPD and n=37 non-COPD controls; age 70 ± 7 yrs; 60M/39F) completed measurements of pulmonary function and common carotid artery stiffness and were retrospectively stratified by self-report of previous clinical diagnosis with OSA. Results: Participants with overlap syndrome had significantly greater carotid β-stiffness than COPD patients without OSA, non-COPD controls with OSA and non-COPD controls without OSA (overlap 5.7 ± 0.71 vs COPD only 3.9 ± 0.20, OSA only 3.6 ± 0.31, controls 3.7 ± 0.23 U; F=6.245, p2 ) or nocturnal mean SpO 2 in those with overlap syndrome vs. the other groups. Furthermore, there was no difference in carotid β-stiffness between overlap syndrome patients that reported using vs. not using a CPAP (5.98 ± 0.7 vs 5.53 ± 1.9 U, p=0.80). Discussion: These data suggest that OSA exacerbates carotid artery stiffening in COPD patients and that carotid artery stiffness may be one mechanism that mediates the increased CVD risk observed in COPD patients with overlap syndrome.

Background Large sample GWAS is needed to identify genetic factors associated with depression. This study used genome-wide genotypic and phenotypic data from the COPDGene study to identify genetic risk factors for depression. Methods Data were from 9716 COPDGene subjects with ≥10 pack-year history. Depression was defined as antidepressant use and/or a HADS depression subscale score ≥8. Non-Hispanic White (6576) and African-American (3140) subsets were analyzed. A GWAS pipeline identified SNPs associated with depression in each group. Network analysis software analyzed gene interactions through common biological pathways, genetic interactions, and tissue-specific gene expression. Results The mean age was 59.4 years (SD 9.0) with 46.5% female subjects. Depression was in 24.7% of the NHW group (1622) and 12.5% of the AA group (391). No SNPs had genome-wide significance. One of the top SNPs, rs12036147 (p = 1.28 × 10−6), is near CHRM3. Another SNP was near MDGA2 (rs17118176, p = 3.52 × 10−6). Top genes formed networks for synaptic transmission with a statistically significant level of more co-expression in brain than other tissues, particularly in the basal ganglia (p = 1.00 × 10−4). Limitations Limitations included a depression definition based on antidepressant use and a limited HADS score subgroup, which could increase false negatives in depressed patients not on antidepressants. Antidepressants used for smoking cessation in non-depressed patients could lead to false positives. Conclusions Systems biology analysis identified statistically significant pathways whereby multiple genes influence depression. The gene set pathway analysis and COPDGene data can help investigate depression in future studies.

Aims: To examine the effects of pioglitazone or endurance exercise training on cognitive function in older adults with mild cognitive impairment (MCI) and insulin resistance. Methods: Seventy-eight adults (mean age ± SD: 65 ± 7 years) with central obesity and MCI were randomized to 6 months of endurance exercise, pioglitazone or control. Results: Sixty-six participants completed the study. Exercise training did not significantly increase peak oxygen uptake compared to control (p = 0.12). Compared to control, insulin resistance improved in the pioglitazone group (p = 0.002) but not in the exercise group (p = 0.25). There was no measureable effect of pioglitazone or exercise on cognitive performance compared to control. Conclusion: In this pilot study, pioglitazone improved insulin resistance but not cognitive performance in older adults with MCI and insulin resistance.

Rationale: Economic factors affect health outcomes in many diseases, including COPD. Aims: Determine the association of low income to symptoms, quality of life and disease progression using longitudinal change in CT-based measures of emphysema and lung function. Methods: 4386 subjects from Phase 2 COPDGene reported annual income. The lowest income group ( Results: The ExtrLo group was significantly younger, with more current smokers, exacerbations (13.2% vs. 6.5%, p Conclusions: Extreme-low-income smokers have more symptoms and less emphysema at baseline but show greater spirometric and radiographic disease progression without signficant change in symptoms over a five year period. Continued high smoking rates may be the key factor in disease progression in this population.

This study examined the association of perceived cognitive difficulties with objective cognitive performance in former smokers. We hypothesized that greater perceived cognitive difficulties would be associated with poorer performance on objective executive and memory tasks.Participants were 95 former smokers recruited from the COPDGene study. They completed questionnaires (including the Cognitive Difficulties Scale [CDS] and the Hospital Anxiety and Depression Scale [HADS]), neuropsychological assessment, and pulmonary function testing. Pearson correlations and t-tests were conducted to examine the bivariate association of the CDS (total score and subscales for attention/concentration, praxis, delayed recall, orientation for persons, temporal orientation, and prospective memory) with each domain of objective cognitive functioning (memory recall, executive functioning/processing speed, visuospatial processing, and language). Simultaneous multiple linear regression was used to further examine all statistically significant bivariate associations. The following covariates were included in all regression models: age, sex, pack-years, premorbid functioning (WRAT-IV Reading), HADS total score, and chronic obstructive pulmonary disease (COPD) status (yes/no based on GOLD criteria).In regression models, greater perceived cognitive difficulties overall (using CDS total score) were associated with poorer performance on executive functioning/processing speed tasks (b = -0.07, SE = 0.03, p = .037). Greater perceived cognitive difficulties on the CDS praxis subscale were associated with poorer performance on executive functioning/processing speed tasks (b = -3.65, SE = 1.25, p = .005), memory recall tasks (b = -4.60, SE = 1.75, p = .010), and language tasks (b = -3.89, SE = 1.39, p = .006).Clinicians should be aware that cognitive complaints may be indicative of problems with the executive functioning/processing speed and memory of former smokers with and without COPD.

Perceived criticism from family members influences mental health. The link between perceived criticism and physical health has not been thoroughly investigated. The objective of this study was to examine the association of perceived criticism with dyspnea in chronic obstructive pulmonary disease (COPD).401 individuals with alpha-1 antitrypsin deficiency-associated COPD completed questionnaires at baseline, 1- and 2-year follow-up. Perceived criticism at baseline was examined as a predictor of dyspnea at all three time points using a linear mixed model that adjusted for demographic and health characteristics.There was an interaction between perceived criticism and psychological distress (p=0.038). Perceived criticism was associated with dyspnea only among individuals with elevated psychological distress (b=0.32, SE=0.13, p=0.018).Further research is needed to replicate these findings and determine the extent to which they apply to other common subjective physical symptoms such as pain.

To determine which aspect of illness uncertainty (i.e., ambiguity or complexity) has a stronger association with psychological and clinical outcomes over a 2-year period among individuals with a genetic subtype of chronic obstructive pulmonary disease (COPD). Ambiguity reflects uncertainty about physical cues and symptoms, and complexity reflects uncertainty about treatment and the medical system.Four-hundred and 7 individuals with alpha-1 antitrypsin deficiency-associated COPD completed questionnaires at baseline, 1- and 2-year follow-up. Uncertainty was measured using the Mishel Uncertainty in Illness Scale. Outcomes were measured using the Hospital Anxiety and Depression Scale, St. George's Respiratory Questionnaire, and MMRC Dyspnea Scale. Ambiguity and complexity were examined as predictors of depressive symptoms, anxiety, quality of life, and breathlessness using linear mixed models adjusting for demographic and health characteristics.Ambiguity was associated with more depressive symptoms (b = 0.09, SE = 0.02, p.001) and anxiety (b = 0.13, SE = 0.02, p.001), worse quality of life (b = 0.57, SE = 0.10, p.001), and more breathlessness (b = 0.02, SE = 0.006, p.001). Complexity did not have an independent effect on any outcome. Interactions between ambiguity and time since diagnosis were not statistically significant.Ambiguity was prospectively associated with worse mood, quality of life, and breathlessness. Thus, ambiguity should be targeted in psychosocial interventions. Time since diagnosis did not affect the association between ambiguity and outcomes, suggesting that the impact of ambiguity is equally strong throughout the course of COPD.

Attempts to understand the causes of cognitive impairment in obstructive sleep apnea (OSA) are complicated by the overlap among clinical and demographic factors that may impact cognition. The goal of the current study was to isolate the contribution of hypoxemia to cognitive impairment in OSA. Two groups of 20 patients with newly diagnosed OSA were compared. The groups differed on severity of hypoxemia but not other demographic (e.g., age, gender, education, estimated premorbid IQ) or clinical (e.g., sleep related respiratory disturbances, daytime sleepiness, depressive symptoms) variables. Participants completed polysonmography and cognitive assessment. We compared patients with high and low hypoxemia on measures of memory, attention, executive functioning, and motor coordination using independent sample t-tests. The high hypoxemia group performed significantly better on immediate recall (Hopkins Verbal Learning Test — Revised; t = −2.50, p

Patients' beliefs about the causes of their illness have been associated with emotional adjustment and behavioral outcomes in several medical conditions; however, few studies have examined illness attributions among patients with chronic obstructive pulmonary disease (COPD). In the current study, patterns of patients' causal attributions for COPD were identified and examined in relation to health behaviors and symptoms.Three-hundred and ninety-four patients with COPD and10 pack year history of smoking completed a self-report questionnaire that included the Illness Perception Questionnaire-Revised (IPQ-R).A factor analysis of the IPQ-R cause items using principal axis factoring yielded four individual items (i.e., smoking, heredity, pollution, and personal behavior) and one large factor that was primarily driven by psychological attributions. Ninety-three percent of patients agreed or strongly agreed that smoking was a cause of their COPD. Higher scores on the large IPQ-R factor were associated with reduced quality of life (r=.25, P.001) and symptoms of anxiety (r=.33, P.001) and depression (r=.31, P.001), indicating that patients who attributed their COPD to psychological factors were more likely to have poorer emotional adjustment and quality of life.Our finding of one large factor with several stand-alone items is in contrast with previous research that has derived a multifactor structure for the cause items of the IPQ-R in other chronic illness populations. This difference may be due to the importance of smoking, environmental exposures, and heredity in the development of COPD. Future research should expand upon these specific attributions in COPD.

Purpose In patients with heart failure, reduced cardiac ejection fraction has been associated with impaired cognition. Improving cardiac function may have beneficial effects on cognition; however, no controlled intervention studies have examined this possibility. Cardiac resynchronization therapy (CRT) is one intervention that has been shown to increase cardiac function. The goals of the current study were to (1) evaluate neuropsychological performance before and 3 months after crt and (2) examine follow-up neuropsychological performance of patients classified on the basis of extent of improved left ventricular ejection fraction (LVEF). Methods Twenty-seven patients with moderate to severe heart failure completed a neuropsychological assessment, 6-minute walk test, and transthoracic echocardiography before and 3 months after CRT. Patients were classified on the basis of improvement in LVEF. Results of a multivariate analysis of variance revealed a significant effect of improvement in LVEF on change in cognition (Wilks Λ, P = .031). Results Patients with improved LVEF demonstrated significant increases on measures of executive functioning (F = 8.57, P = .007) and visuospatial function (F = 7.52, P = .011) and less decline on global cognition (F = 5.73, P = .024) than those without LVEF improvement. Conclusions Findings provide preliminary evidence that improved LVEF in response to CRT is associated with enhanced cognitive outcomes within 3 months of CRT. Patients with improved LVEF showed better outcomes on measures of executive functioning, global cognition, and visuospatial functioning. Future, controlled, large-scale trials will be necessary to determine whether there is an underlying causal relationship linking increase in LVEF and cognition.

Objective: Elderly patients with cardiovascular disease (CVD) often report cognitive difficulties including reduced cognitive processing speed and attention. On cross-sectional examination, such reports relate more closely to mood than to objective measures of cognitive performance, thus questioning the validity of subjective cognitive complaints as a marker of neurodegenerative processes. This study examined the longitudinal relationship among self-reported cognitive difficulties, depression, and performance on objective tests of global cognition in patients with CVD. Participants and Methods: Forty-seven patients with CVD (aged 55–85 years) completed a measure of perceived cognitive dysfunction (Cognitive Difficulties Scale [CDS]), a medical history questionnaire, the Dementia Rating Scale (DRS), and the Beck Depression Inventory (BDI) at baseline and 12 months later. Baseline brain imaging was available on a small subsample (N = 17). Results: Hierarchical linear regression revealed that increased report of cognitive difficulties at baseline was significantly associated with poorer DRS performance at follow-up (F [3, 43] = 4.45, p=0.008, CDS partial r=−0.30, p=0.048), independent of age, education, baseline DRS, and BDI scores. Greater perceived cognitive dysfunction at baseline also related to higher level of white matter lesions (r = 0.53, df=15, p=0.028). Conclusions: Self-reported cognitive difficulties may reflect early changes in cognitive aging that are difficult to detect using global cognitive screening measures at a single time point. However, these perceived difficulties relate to objectively measured cognitive decline over time. Thus, they may provide important clinical information about early neurodegenerative processes that should be carefully monitored.

Past studies link elevated blood pressure (BP) and BP variability to adverse neurocognitive changes in community samples. However, little is known about the relationship between BP indices and cognitive function in older CVD patients.A total of 99 older adults with CVD completed a comprehensive neuropsychological test battery. Resting BP measurements were collected every 10 min for 2 hr during a separate cardiac assessment. Five BP indices were generated: average and standard deviation of systolic blood pressure (SBP), average and standard deviation of diastolic blood pressure (DBP), and a function of systolic variability and average diastolic pressure. We examined the relationship between these BP indices and cognitive function.Partial correlation adjusting for age and education revealed that the function of systolic variability and average diastolic pressure (SBP standard deviation divided by the average DBP) was most closely related to test performance, showing significant associations to both Learning/Memory (r = 0.25) and Language functioning (r = 0.22). SBP indices were also related to Language functioning (SBP avg., r = 0.22; SBP SD, r = 0.25), though DBP indices were unrelated to performance in any cognitive domain.The current findings indicate that BP is modestly related to cognitive function in older CVD patients. Contrary to expectations, greater BP variability was associated with better, not poorer, cognitive test performance. Such findings suggest that the relationship between BP and cognitive function is more complicated than typically believed and requires further examination.

This study examines the relationship between systemic vascular function, neurocognitive performance, and structural brain abnormalities on magnetic resonance imaging (MRI) among geriatric outpatients with treated, stable cardiovascular disease and no history of neurological illness (n = 88, ages 56-85 years). Vascular function was assessed by cardiac ejection fraction and output, sequential systolic and diastolic blood pressures, flow mediated brachial artery reactivity (BAR), and carotid intima media thickness (IMT). White matter hyperintensities (WMH) on MRI were quantified and examined relative to cognitive and vascular function. Principal component analysis revealed two primary vascular components: one associated with cardiac function, the other with atherosclerotic burden/endothelial dysfunction. Both factors were significantly associated with cognitive function and WMH volume. Reduced systolic variability and increased IMT were most strongly related to reduced attention, executive function, and information-processing speed. These findings suggest the possibility that systemic vascular indices may provide proxy measures of cerebrovascular dysfunction and reinforce the importance of achieving greater understanding of interaction between systemic vascular disease and brain dysfunction among elderly people with cardiovascular disease.

The purpose of this study was to investigate the relations between regional white matter signal abnormalities (WMSA) and cognitive functioning among individuals being treated for cardiovascular risk factors and/or clinical events. Forty-one participants with cardiovascular disease underwent a comprehensive neuropsychological assessment and MRI. Total WMSAs were quantified using a semi-automated thresholding technique. Unique to this study, total WMSA volume was divided into three separate anatomically related regions: WMSA in the periventricular (PERIWMSA) region, WMSA adjacent to subcortical nuclei (SUBWMSA), and WMSA in the deep white matter (DEEPWMSA). A ratio of these measures to total cerebral brain volume was compared to cognitive measures assessing attention, executive functioning, psychomotor speed, immediate and delayed memory, language, and visuospatial functioning. PERIWMSA, SUBWMSA, and total WMSA were significantly associated with performance on measures of attention/processing speed. No other significant relationships between WMSA and cognition were noted. Secondary analyses suggested that PERIWMSA volume was increased in individuals with clinical evidence of atherosclerosis. These results emphasize the utility of studying the associations between regional WMSA and cognitive/functional performance in patients undergoing cardiovascular treatment.

We previously reported a relationship between forearm resistance vessel function and global neuropsychological performance in patients with atherosclerotic vascular disease (AVD). This study was conducted to determine the relationships among vascular smooth muscle function, endothelial function, and initiation and processing speed in this sample. Participants were 80 individuals with AVD. Resistance vessel function was measured before and after infusion of vasoactive agents. Neuropsychological assessment included measures of estimated premorbid cognitive function, current global cognitive function, initiation, and processing speed. Vascular smooth muscle function was significantly associated with the initiation/processing speed composite score [R-Square Change = .152; F Change (1,71) = 16.61; p < .001], above and beyond the variance accounted for by age, education, premorbid cognitive function, and endothelium-dependent vascular function. This relationship remained significant when controlling for current level of global cognitive functioning and 10 vascular risk factors. Endothelium-dependent vascular function was not significantly associated with test performance. Decreased vascular smooth muscle function in forearm resistance vessels was significantly associated with relatively poor initiation and processing speed in individuals with AVD. With additional research, measures of vascular function might become useful in the early identification of those individuals at greatest risk for vascular-related cognitive dysfunction. (JINS, 2008, 14, 535–541.)

Increased carotid artery intima-media thickness (IMT) is a non-invasive marker of systemic arterial disease. Increased IMT has been associated with atherosclerosis, abnormal arterial mechanics, myocardial infarction, and stroke. Given evidence of a relationship between cardiovascular health and attention-executive-psychomotor functioning, the purpose of this study was to examine IMT in relation to neuropsychological test performance in patients with a variety of cardiovascular diagnoses.One hundred and nine participants, ages 55 to 85, underwent neuropsychological assessment and B-mode ultrasound of the left common carotid artery. IMT was calculated using an automated algorithm based on a validated edge-detection technique. The relationship between IMT and measures of language, memory, visual-spatial abilities and attention-executive-psychomotor functioning was modeled using hierarchical linear regression analyses adjusted for age, education, sex, cardiovascular risk, current systolic blood pressure, and history of coronary artery disease (CAD).Increased IMT was associated with significantly lower performance in the attention-executive-psychomotor domain (IMT beta=-0.26, p.01), independent of age, education, sex, cardiovascular risk, current systolic blood pressure, and CAD (F(10,100)=3.61, p.001). IMT was not significantly related to language, memory, or visual-spatial abilities.Our findings suggest that, in patients with cardiovascular disease, IMT may be associated with the integrity of frontal subcortical networks responsible for attention-executive-psychomotor performance. Future studies are needed to clarify the mechanisms by which IMT affects cognition and examine potential interactions between increased IMT and other measures of cardiovascular health such as blood pressure variability, cardiac systolic performance, and systemic perfusion.

Background and Purpose— The presence of white matter hyperintensities on brain MRI is common among elderly individuals. Previous research suggests that cardiovascular risk factors are associated with increased white matter hyperintensities. Examining the role of direct physiological measures of vascular function will help to clarify the vascular mechanisms related to white matter hyperintensities. The aim of the present study was to examine the association between endothelial-dependent and endothelial-independent vasodilatation and white matter hyperintensity volume. Methods— Twenty-five older adults with a range of cardiovascular diseases underwent brain MRI and completed assessments of blood vessel integrity using endothelial-dependent and independent flow-mediated dilation of the brachial artery. A semi-automated pixel-based method was used to quantify total brain volume and white matter hyperintensity volume, with white matter hyperintensity volume corrected for total brain volume. The association between measures of flow-mediated dilation and log-transformed white matter hyperintensities was examined. Results— Correlation analysis revealed that endothelial-dependent vasodilatation was significantly and inversely associated with white matter hyperintensity volume. In contrast, endothelial-independent vasodilatation was not associated with white matter hyperintensities. Neither endothelial-dependent nor endothelial-independent vasodilatation was associated with total brain volume. Conclusions— These data provide preliminary evidence that the integrity of the vascular endothelium is associated with white matter hyperintensities in older adults with cardiovascular disease. Impaired vascular function may be one mechanism that contributes to the development of white matter hyperintensities in the brain. Additional longitudinal research combining measures of vessel function, neuroimaging and cognition will be helpful in clarifying this potential mechanism.

Research examining the role of social support in patient adjustment to chronic illness has been inconsistent suggesting that patient individual differences play a moderating role. This study examined the hypothesis that the relationship between social support and depressive symptoms would differ as a function of individual differences in trait Agreeableness. Fifty-nine patients with chronic kidney disease were assessed using the Social Provisions Scale, Beck Depression Inventory and NEO-Five-Factor Inventory and were followed-up a year and a half later. After controlling for baseline depressive symptoms and clinical characteristics, regression analyses revealed a significant interaction between social support and Agreeableness predicting change in depressive symptoms. Greater social support among individuals high in Agreeableness was associated with a decrease in depressive symptoms over time, while support had little effect on depression change for individuals low in Agreeableness. These findings underscore the importance of individual difference variables in understanding adjustment to chronic illness.

Younger persons with COPD report worse health-related quality of life (HRQL) than do older individuals. The factors explaining these differences remain unclear. The objective of this article was to explore factors associated with age-related differences in HRQL in COPD.Cross-sectional analysis of participants with COPD, any Global Initiative for Chronic Obstructive Lung Disease grade of airflow limitation, and ≥ 50 years old in two cohorts: the Genetic Epidemiology of COPD (COPDGene) study and the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS). We compared St. George's Respiratory Questionnaire (SGRQ) scores by age group: middle-aged (age, 50-64) vs older (age, 65-80) adults. We used multivariate linear modeling to test associations of age with HRQL, adjusting for demographic and clinical characteristics and comorbidities.Among 4,097 participants in the COPDGene study (2,170 middle-aged and 1,927 older adults) SGRQ total scores were higher (worse) among middle-aged (mean difference, -4.2 points; 95% CI, -5.7 to -2.6; P.001) than older adults. Age had a statistically significant interaction with dyspnea (P.001). Greater dyspnea severity (modified Medical Research Council ≥ 2, compared with 0-1) had a stronger association with SGRQ score among middle-aged (β, 24.6; 95% CI, 23.2-25.9) than older-adult (β, 21.0; 95% CI, 19.6-22.3) participants. In analyses using SGRQ as outcome in 1,522 participants in SPIROMICS (598 middle-aged and 924 older adults), we found similar associations, confirming that for the same severity of dyspnea there is a stronger association with HRQL among younger individuals.Age-related differences in HRQL may be explained by a higher impact of dyspnea among younger subjects with COPD.ClinicalTrials.gov; No.: NCT00608764 and No.: NCT01969344; URL: www.clinicaltrials.gov.

Illness uncertainty is associated with worse outcomes in patients with chronic health conditions. Research on social factors associated with uncertainty has focused on the beneficial role of social support. The goal of this study was to develop a more nuanced understanding of the social factors that are associated with uncertainty. Four hundred sixty-two individuals with alpha-1 antitrypsin deficiency (AATD)-associated chronic obstructive pulmonary disease (COPD) completed a mailed questionnaire. Measures of the social environment included general family functioning, perceived criticism from family members, whether the participant had family members with AATD or COPD, and participation in support groups. Uncertainty was measured using the Mishel Uncertainty in Illness Scale including subscales for ambiguity (uncertainty about physical cues and symptoms) and complexity (uncertainty about treatment and the medical system). Hierarchical regression was used to identify social correlates of ambiguity and complexity while adjusting for demographic and medical characteristics and psychological distress. Perceived criticism was associated with more complexity (b = 0.21, SE = 0.09, p = 0.015) and ambiguity (b = 0.40, SE = 0.12, p = 0.001). Having a family member with AATD or COPD was associated with more ambiguity (b = 3.28, SE = 1.00, p = 0.001). Participation in support groups was associated with less ambiguity. Individuals who attended three or more support groups in the prior year reported less ambiguity than individuals who had not attended any (b = −3.31, SE = 1.29, p = 0.010). The social environment is complex and encompasses more than social support. Multiple aspects of the social environment are associated with uncertainty, including perceived criticism, having a family member with a similar illness, and participation in support groups.

Cardiovascular disease (CVD) is a risk factor for cognitive impairment and dementia. Recent studies implicate homocysteine (HCY) and C-reactive protein (CRP) in this increased risk, as both are associated with cognitive dysfunction in demented and non-demented patients. However, it remains unclear whether they confer added risk in older adults with CVD. A total of 126 older CVD patients underwent blood and neuropsychological evaluation as part of a prospective examination of the neurocognitive consequences of CVD. A subset of these participants (n = 37) also underwent neuroimaging to quantify the degree of white matter disease. After adjusting for demographic and medical factors, no significant relationship emerged between HCY and cognitive performance. In contrast, CRP showed significant independent relationships to test performance, including global cognitive performance, attention/psychomotor function, executive function, memory, and visuospatial abilities. Neither HCY nor CRP was related to extent of white matter disease or whole brain volume on magnetic resonance imaging. Further study is needed to identify mechanisms by which inflammatory processes impact on cognitive function and to determine whether reducing circulating levels of inflammatory markers results in improved cognition.

Efforts to identify genetic factors that confer an increased risk for the expression of psychiatric symptoms have focused on polymorphisms in variety of candidate genes, including the catechol-O-methyltransferase (COMT) gene. Results from previous studies that have examined associations between the functional COMT polymorphism (Val158Met) and mental health have been mixed. In the present study, we examined the relationships between COMT, early life stress, and personality in a healthy adult sample. Consistent with previous studies, we hypothesized that individuals with the low-activity genotype would have higher neuroticism and lower extraversion and that this effect would be more pronounced in females. In addition, we extended the previous literature by investigating the potential influence of early life stress. A total of 486 healthy adults underwent genetic testing and personality assessment. Results revealed that individuals homozygous for the COMT low enzyme activity allele had lower extraversion on the NEO-FFI and demonstrated a trend toward greater neuroticism. These relationships were not influenced by sex or the presence of reported early life stress. The finding that COMT genotype was associated with extraversion, and more weakly with neuroticism, is consistent with previous studies. Future research to clarify the influence of sex and gene-environmental interactions is warranted.

Older adults with cardiovascular disease (CVD) often report experiencing significant cognitive dysfunction in everyday life and exhibit deficits on neuropsychological testing. However, the relationship between subjective and objective cognitive dysfunction is inconsistent across studies and requires closer examination. Participants included 84 older adults with documented CVD and no history of neurological or severe psychiatric disorder. All participants underwent echocardiogram and neuropsychological assessment and completed self-report measures of perceived cognitive dysfunction, depression, and health-related quality of life. Results showed that concerns regarding distractibility and sustained attention were most common. Level of reported cognitive dysfunction was significantly related to depressive symptoms, quality of life, and performance on multiple cognitive tests. Exploratory regression analyses showed that depressive symptoms, physical health-related quality of life, and speeded sustained attention predicted reports of cognitive dysfunction, whereas demographic variables, cardiac output, and other cognitive tests did not. Should they be replicated, these findings suggest that reports of cognitive dysfunction in older adults with CVD largely reflect depressive symptoms and reduced quality of life.

In the present study, we examined the relationships between whole brain volume (WBV), subcortical hyperintensities (SH), indices of cardiac disease and cognitive function in nondemented cardiac patients with evidence of mild cerebrovascular disease. A total of 27 individuals with evidence of cardiac disease underwent neuropsychological examination, neuroimaging, and cardiac assessment. Cognition was assessed with the Dementia Rating Scale-2 (DRS). WBV and SH were quantified using a semi-automated thresholding program based on MRI. Correlational analyses revealed that WBV predicted performance on the overall DRS score, the attention subscale and the initiation/perseveration scale. SH were significantly associated with performance on the attention subscale, and the initiation/perseveration subscale. Regression analyses revealed that SH accounted for most of the variance in the initiation/perseveration scale, whereas WBV accounted for most of the variance in the attention scale. The only cardiac structural or functional variable related to the neurological indices was aortic diameter, which was strongly related to both neuroimaging variables, as well as performances on the DRS attention and initiation/perseveration subscales. Our results highlight the importance of overall brain parenchyma in determining cognitive status among patients at risk for cognitive decline and suggest that select indices of structural cardiac morphology may be related to the early phases of cerebrovascular disease and cognitive status.

The present study examined the relationship between multiple blood pressure (BP) indices and white matter hyperintensities (WMH) in a sample of 39 older adults with cardiovascular disease (CVD). Resting BP was measured using an automated monitor every 10 min for 2 h. WMH were quantified on FLAIR images and separate indices were generated for neocortical, periventricular and subcortical brain regions. Correlation analyses revealed systolic BP variability was related to neocortical and total WMH. A function of systolic BP variability and average diastolic pressure showed the strongest relationships, including significant correlation to neocortical, subcortical and total WMH. No BP index was related to WMH in periventricular regions. Exploratory analyses showed only the function of systolic BP variability and average diastolic pressure predicted total WMH, whereas as age, CVD conditions and psychosocial factors did not. These findings demonstrate BP variability is an important contributor to WMH in older adults with CVD and suggests it may have differential relationships to WMH in different brain regions. Additional studies are needed to examine the role of autoregulatory systems in the development of WMH, particularly those using beat-to-beat measures of BP.

Background: Early stages of chronic obstructive pulmonary disease (COPD) are characterized by loss of the terminal bronchioles and ‘air trapping’ often before overt emphysema manifests (1). COPD patients are also at risk for cardiovascular disease (CVD), therefore, we hypothesized that the degree of air trapping on computed tomography (CT) (2) would be associated with higher aortic (carotid femoral pulse wave velocity, CFPWV) and carotid artery stiffness (β-stiffness), biomarkers of CVD risk. Methods: Ten adults with COPD but little emphysema (age 66±8 yrs, 5F/5M, GOLD stage 1–3) and 9 adults without COPD (age 59±13 yrs, 5F/4M) that had a research chest CT were recruited. Results: COPD patients had greater smoking history (45.9 ± 21 vs. 6.4 ± 12.9 pack-years, P0.05). COPD patients had significantly higher CFPWV (999± 293 vs. 760 ±147 cm/sec, p

Excessive alcohol use in COPD has been associated with increased mortality; however, little is known about alcohol use in AATD-associated COPD. A total of 538 individuals with AATD-associated COPD completed questionnaires at baseline and 330 also completed 2 years of follow-up questionnaires. Demographic and health information was collected, including information about alcohol use, ER visits for COPD, and hospitalizations for COPD. Problem alcohol use was characterized using the CAGE screening questionnaire and recent alcohol consumption. Demographic and clinical characteristics associated with problem drinking were identified using logistic regression. Problem drinking at baseline was examined as a predictor of ER visits and hospital admissions for COPD in the subsequent two years using logistic regression adjusting for demographic variables and baseline health status. 14% of the sample reported a history of problem drinking per the CAGE and 8% reported problem drinking in the past week. Problem drinking was associated with higher education and greater lifetime tobacco exposure. Recent alcohol consumption was a significant predictor of having an ER visit for COPD in the subsequent two years. Compared to individuals who reported problem drinking in the past week, individuals with no consumption (OR = 0.32, 95% CI = 0.10 to 0.97, p = .043) and individuals with low-to-moderate consumption (OR = 0.25, 95% CI = 0.08 to 0.77, p = .016) had significantly lower odds of an ER visit. Neither measure of problem drinking predicted hospital admission. Screening for recent excessive alcohol use in this population may identify individuals at risk for use of costly emergency health services.

Emphysema is a chronic progressive pulmonary disease with significant physical, cognitive and psychological sequelae. Patients with moderate to severe emphysema exhibit cognitive deficits across a variety of domains.1-6 Emphysema represents a subset of patients with chronic obstructive pulmonary disease (COPD), and data on patients with COPD are relevant to understanding cognitive impairment in emphysema. In COPD patients with moderate to severe hypoxemia, deficits have been reported in psychomotor speed, perceptual-motor integration, abstract reasoning, attention to auditory stimuli, learning and memory, and language skills.2,3,5-7 Several studies have found that psychomotor speed and aspects of executive functioning are the cognitive areas most consistently affected by COPD.8-10 The Trail Making Test (TMT) is a common measure of visuomotor speed and executive functioning.11 It has 2 parts, which measure visuomotor processing speed (TMT-Part A) and set shifting and maintenance of effort (TMT-Part B). Impaired executive functioning has been associated with poorer instrumental daily activities in older adults.12 For example, 1 study of 7717 elderly women demonstrated that impaired executive functioning, measured using the TMT-Part B, was more strongly associated with decline in activities of daily living over 6 years than global cognitive function.13 These findings suggest that impairments in executive functioning, including visuomotor speed and sequential ability, have important practical implications for older adults. Patients with COPD perform worse on the TMT than age matched controls.5,9,10 In “end-stage” COPD patients, Crew et al8 found that more patients did poorly on TMT-Part B than TMT-Part A. The authors concluded that patients had greater difficulties with set shifting skills and maintenance of response strategies than pure slowing of processing speed. Another study found impairments in both Trail Making Test Part A and B.10 There is evidence that oxygen therapy, pulmonary rehabilitation and exercise interventions improve cognitive functions in emphysema and COPD.4,14-17 The mechanisms associated with improved processing speed and sequencing include enhanced exercise capacity and cerebral oxygenation.18 Lung volume reduction surgery (LVRS) is a procedure performed on COPD patients that affects both exercise capacity and oxygenation.19 Previous studies from our group compared the neuropsychological profile of 19 patients following lung volume reduction surgery (LVRS) and 20 patients following standard medical therapy (MT) using data collected at 2 of the 17 sites participating in the National Emphysema Treatment Trial (NETT).20 Participants completed a comprehensive neuropsychological battery including TMT at baseline, prerandomization (6-10 weeks following rehabilitation), and 6 months after randomization. Initial findings suggested that 6 months after randomization to LVRS or MT, LVRS patients had significantly improved performance on several cognitive tests, including the TMT Parts A and B. 21 Subjects in the main NETT study completed TMT at baseline, prerandomization (following 6-10 weeks multidisciplinary rehabilitation), 12 months, and yearly for up to 5 years. In the current study we sought to extend the scope and length of followup in our previous cognitive studies to determine whether the cognitive improvement observed at 6 months in a subsample of NETT participants would be evident in the larger sample at 2-year followup. The current study examined changes in the psychomotor speed and sequencing skills of emphysema patients randomized to either LVRS or to MT with data collected at 15 clinic sites (excluding the 2 sites previously examined at 6 months20). We hypothesized that at 2-year followup patients randomized to LVRS would exhibit better performance on psychomotor speed and sequencing skills on the TMT Parts A and B than patients randomized to MT.

BACKGROUND AND PURPOSE: MetS is a cluster of risk factors associated with significant cardiovascular morbidity and mortality and diminished cognitive function. Given that little is known about the early signs of brain vulnerability related to persistent metabolic dysfunction, we set out to determine whether cognitively healthy middle-aged individuals with MetS exhibit an altered cerebrovascular response to a cognitive challenge relative to those without MetS. MATERIALS AND METHODS: Forty neurologically healthy adults aged 40–60 years (19 with MetS and 21 healthy controls) performed a 2-back verbal working memory task during fMRI. We compared BOLD responses between the 2 groups in 8 a priori regions of interest previously shown to be associated with the 2-back in patients with cardiovascular disease. RESULTS: Age, education level, sex distribution, cognitive and emotional functioning, and task performance (accuracy and reaction time) were not different between the groups. Compared with healthy controls, individuals with MetS demonstrated a lower 2-back–related BOLD response in the right superior frontal gyrus, right superior parietal lobule, and left inferior parietal lobule. CONCLUSIONS: This study provides preliminary evidence that cognitively intact middle-aged individuals with MetS exhibit significant alterations in cerebrovascular response to a cognitive challenge. Our results also demonstrate that fMRI may identify early brain changes associated with MetS.

Background and Purpose— There is growing evidence that the cell adhesion molecule P-selectin (SELP) contributes to the adverse vascular processes that promote cognitive impairment in individuals with cardiovascular disease. Previous research has shown that SELP genotypes moderate circulating levels of P-selectin and that patients undergoing coronary artery bypass graft with the SELP 1087A allele were less likely to show postoperative cognitive decline and more likely to exhibit lower levels of C-reactive protein than noncarriers. Thus, we expected that carriers of the 1087A allele (n=43) would exhibit better cognitive functioning than persons with 2 1087G alleles (n=77) and that C-reactive protein levels would be important for this relationship. Methods— One hundred twenty older adults with diagnosed cardiovascular disease were recruited from outpatient cardiology clinics. Each participant underwent a comprehensive neuropsychological test battery and a blood draw. Results— Participants with the SELP 1087A allele performed more poorly on tests of attention (Trail Making Test A: t[116]=3.20, P =0.002), executive function (Trail Making Test B: t[116]=2.89, P =0.005), psychomotor speed (Digit–Symbol Coding: t[117]=2.54, P =0.012), and memory (California Verbal Learning Test Discrimination: t[116]=2.05, P =0.04). There were no significant differences between the SELP genotype groups on demographic/medical variables or C-reactive protein levels. Conclusions— Contrary to expectations, the present analyses showed that older patients with cardiovascular disease with the SELP 1087A allele performed more poorly on neuropsychological testing. Findings from the present study were counter to previous research with coronary artery bypass graft candidates. Further work using neuroimaging and alternative measures of cardiovascular function is needed to clarify the mechanisms of this association.

Cardiovascular disease (CVD) and particularly heart failure (HF) have been associated with cognitive impairment in cross-sectional studies, but it is unclear how cognitive impairment progresses over time in older adults with these conditions.The aim of this study was to prospectively examine cognitive function in patients with HF versus other forms of CVD.Seventy-five older adults (aged 53-84 years) with CVD underwent Doppler echocardiogram to evaluate cardiac status and 2 administrations of the Dementia Rating Scale (DRS), a test of global cognitive functioning, 12 months apart.Although DRS performance did not statistically differ between groups at either administration, a significant between-group difference in the rate of cognitive change emerged (lambda = 0.87; F = 10.50; P = .002; omega 2 = 0.11). Follow-up analyses revealed that patients with HF improved significantly on global DRS performance, whereas patients with other forms of CVD remained stable. More specifically, patients with HF showed improvement on subscales of attention, initiation/perseveration, and conceptualization. Exploratory analyses indicated that higher diastolic blood pressure at baseline was associated with improved DRS performance in patients with HF (r = 0.38; P = .02).Patients with HF exhibited modest cognitive improvements during 12 months, particularly in attention and executive functioning. Higher diastolic blood pressure at baseline was associated with improvement. These results suggest that cognitive impairment in patients with HF may be modifiable and that improved blood pressure control may be an important contributor to improved function. Further prospective studies are needed to replicate results and determine underlying mechanisms.

Poor cardiac pumping efficiency has shown to lead to cognitive impairments in patients with cardiovascular disease (CVD). The current study examined the relationship between left ventricular ejection fraction and sustained attention and inhibitory processes measured by the Adaptive Rate Continuous Performance Task and the Go/No-go test. Participants were 67 older outpatients (age 68.5 ± 7.4) with a range of CVD. Associations between cognition and ejection fraction were examinedvialinear regression analysis. Results were consistent with the hypothesis that lower ejection fraction is significantly associated with decrements in sustained attention and vigilance. Overall, the results provide support for the hypothesis that a change in cardiac pumping leads to decrements in some aspects of attention; however, inhibitory processes are relatively spared. (JINS, 2009,15, 137–141.)

To prospectively relate C-reactive protein (CRP), a systemic marker of inflammation, to cognitive change over a 1-year follow-up period.Prospective 1-year follow-up.Outpatient university medical setting.Seventy-eight adults (aged 56-84; 39% female) with cardiovascular disease.CRP levels were measured using a high-sensitivity assay, and participants completed a neuropsychological battery at study entry. Neuropsychological assessment was repeated 1 year later.The association between CRP and change in cognition over the 1-year follow-up was examined using hierarchical linear regression modeling for five cognitive domains (global cognition, language, memory, visuospatial abilities, and attention-executive-psychomotor). High CRP levels were associated with subtle declines in attention-executive-psychomotor performance (CRP beta=-0.22, P=.04) after adjusting for the effects of age and cognitive performance at study entry. CRP was not significantly associated with change in language, memory, or visuospatial performance.These data provide preliminary evidence that inflammation, potentially contributing to atherosclerotic processes, may underlie the association between high CRP and changes in attention-executive-psychomotor performance.

To characterize cognition in patients with moderate to severe heart failure and examine the association between 2 measures of systemic perfusion (ie, ejection fraction and cardiac index) and cognition.Decreased systemic perfusion has been implicated as an etiologic factor in the development of cognitive deficits in cardiovascular disease.Thirty-one patients with moderate to severe heart failure and 31 patients with cardiovascular disease and no heart failure completed a medical history interview and neuropsychologic assessment. Participants with heart failure additionally underwent an echocardiogram to assess cardiac function.Patients with heart failure performed significantly worse than the cardiovascular disease-no heart failure group on several measures of executive functioning and psychomotor speed. Among the heart failure group, lower ejection fraction was associated with weaker global cognition, performance on several, but not all, measures of executive functioning, and was marginally associated with delayed memory. Decreased cardiac index was associated with poorer immediate memory and weakly associated with global cognition.Findings suggest that depressed systemic perfusion is associated with cognitive deficits among patients with heart failure. Research including measures of cardiac function, cerebral perfusion, and cognition will be necessary to clarify the causal nature of the suggested mechanism.

Cardiac resynchronization therapy (CRT) improves heart failure (HF) symptoms in patients (pts) with EF 120ms, and NYHA class 3 and 4 HF. The aim of this study was to compare the effects of CRT in pts with EF 130, and class 2 vs 3/4 HF. We enrolled 25 patients. All received ECGs, transthoracic echocardiograms, 6 minute walk tests, and Minnesota quality of life questionnaires pre-op and three months post-op. Fourteen pts were class 2, 10 patients were class 3, and 1 class 4. Ischemic cardiomyopathy accounted for 7 out of the 14 class 2 pts and 5 out of the 11 class 3/4 pts. As a group, all patients had a significant increase in 6 minute walk (1150 vs 1249, p=0.02), increase in EF (30% vs 39%, p ). Nonischemic pts had greater response than ischemic pts. Class 2 HF pts reported greater improvement in mental health than class 3 and 4. Younger patients reported greater functional improvement, while pts with higher BMI reported less physical benefit. Summary: Pts with NYHA class 2 symptoms derive similar hemodynamic benefit from CRT as pts with class 3/4 symptoms and may derive greater mental health benefits than class 3/4 pts. Comparison of Pre and Post-Implant Parameters Between Class 2 and 3/4 Patients

The clinical literature in Huntington's disease (HD) suggests that unawareness of deficits is prevalent among HD patients. However, few studies have characterized unawareness of different types of impairment within this neuropsychiatric disorder. The purpose of the current study was to examine self-awareness of functioning across symptom domains in HD patients and to explore the association between impaired awareness and cognitive dysfunction. A total of 66 pairs of HD patients and collaterals of the patients completed symptom-rating measures regarding both the patients' and the collaterals' behavior. A subset of 19 patients also underwent neurological and neuropsychological assessments. The results indicated that patients lacked awareness across symptom domains (i.e., behavioral control, emotional control, activities of daily living), which was significantly greater for their perception of their own behavior than for their perception of their collateral's behavior. Exploratory analyses revealed associations between impaired self-awareness, global cognition, and deficits in executive functioning and memory. The current findings underscore the importance of examining different types of impaired awareness including both over- and underreporting of abilities. Future studies will benefit also from examining the association between awareness and cognition in larger samples.

Objective: The present study examined the relationship between multiple indices of blood pressure (BP) and cognitive function (as measured by the Dementia Rating Scale). Background: Cardiovascular disease (CVD) is associated with cognitive dysfunction and cerebrovascular pathology in the elderly and is a known risk factor for stroke and Alzheimer disease. Yet, the mechanisms for the effects of CVD on cognitive function are not well understood. Methods: Participants were 97 nondemented older adults with CVD who underwent neuropsychologic assessment, and a 2-hour cardiovascular laboratory protocol. Results: After controlling for age and years of education, results of hierarchical linear regression analyses indicate a significant positive relationship between a function of BP variability (SD of systolic BP divided by the average diastolic BP) and cognitive function (R 2 change = 0.042, F (1, 85) = 5.434, P < 0.05). No relationship emerged between any other BP index and cognitive function. Conclusions: Contrary to expectations, greater BP variability was associated with better, not poorer, cognitive test performance. These findings suggest that the relationship between BP and cognitive function is more complicated than originally conceptualized and requires further investigation.

Aims: The purpose of the present case is to describe the functional outcome of a patient with human immunodeficiency virus (HIV) and progressive multifocal leukoencephalopathy (PML) on treatment with antiretroviral therapy using a multidisciplinary approach. Methods: Neuropsychological tests and diffusion tensor imaging (DTI) were obtained at baseline and after 12 months to define the severity of white matter damage. Neuropsychological and neuroimaging data were compared to an HIV-infected patient without PML and with good immune system health, and to a second HIV-infected patient without PML but with notable immunosuppression. Results: Review of the HIV/PML patient's cognitive data at both time points revealed significant impairments compared to the control subjects. Similarly, the HIV/PML patient's white matter lesion load and whole brain volume were markedly different from the control subjects at both time points. The tractography-defined metrics suggest significant white matter fiber loss associated with HIV/PML that was not evident in either HIV control patient. Discussion: Our findings suggest that PML is associated with marked cognitive and neuroimaging abnormalities in the context of antiretroviral therapy. Integrative Significance: To our knowledge this is the first study to integrate both quantitative DTI and cognitive assessment to define white matter damage associated with HIV and PML. This integrative approach provides a robust methodology to examine the integrity of brain systems mediating cognitive function.

Individuals with manifest Huntington's disease (HD) were interviewed with regard to the presence, frequency, and severity of depression symptoms to better characterize depressed mood across the disease course in HD. Rates of depression were more than twice that found in the general population. One-half reported that they had sought treatment for depression, and more than 10% reported having at least one suicide attempt. The proportion of HD patients endorsing significant depression diminished with disease progression. Despite the public health impact of depression, available treatments are underutilized in HD, and research is needed to document the efficacy and effectiveness of standard depression treatments in this population.

Background Early life stress (ELS) is linked to adult psychopathology and may contribute to long-term brain alterations, as suggested by studies of women who suffered childhood sexual abuse. We examine whether reported adverse ELS defined as stressful and/or traumatic adverse childhood events (ACEs) is associated with smaller limbic and basal ganglia volumes. Method 265 healthy Australian men and women without psychopathology or brain disorders were studied. ACEs were assessed by the ELSQ and current emotional state by the DASS. Anterior cingulate cortex (ACC), hippocampus, amygdala, and caudate nucleus volumes were measured from T1-weighted MRI. Analyses examined ROI volumetric associations with reported ACEs and DASS scores. Results Participants with greater than two ACEs had smaller ACC and caudate nuclei than those without ACEs. A significant association between total ACEs and ROI volumes for these structures was observed. Regression analysis also revealed that ELS was more strongly associated than current emotional state (DASS) with these ROI volumes. Conclusions Reported ELS is associated with smaller ACC and caudate volumes, but not the hippocampal or amygdala volumes. The reasons for these brain effects are not entirely clear, but may reflect the influence of early stress and traumatic events on the developing brain.