Functional Impairment In Subjects Research Articles

Anhedonia as a Potential Risk Factor of Alzheimer's Disease in a Community-Dwelling Elderly Sample: Results from the ZARADEMP Project.

(1) Introduction: Dementia is a major public health problem, and Alzheimer’s disease (AD) is the most frequent subtype. Clarifying the potential risk factors is necessary in order to improve dementia-prevention strategies and quality of life. Here, our purpose was to investigate the role of the absence of hedonic tone; anhedonia, understood as the reduction on previous enjoyable daily activities, which occasionally is underdetected and underdiagnosed; and the risk of developing AD in a cognitively unimpaired and non-depressed population sample. (2) Method: We used data from the Zaragoza Dementia and Depression (ZARADEMP) project, a longitudinal epidemiological study on dementia and depression. After excluding subjects with dementia, a sample of 2830 dwellers aged ≥65 years was followed for 4.5 years. The geriatric mental state examination was used to identify cases of anhedonia. AD was diagnosed by a panel of research psychiatrists according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. A multivariate survival analysis and Cox proportional hazards regression model were performed, and the analysis was controlled by an analysis for the presence of clinically significant depression. (3) Results: We found a significant association between anhedonia cases and AD risk in the univariate analysis (hazard ratio (HR): 2.37; 95% CI: 1.04–5.40). This association persisted more strongly in the fully adjusted model. (4) Conclusions: Identifying cognitively intact individuals with anhedonia is a priority to implement preventive strategies that could delay the progression of cognitive and functional impairment in subjects at risk of AD.

Theory of Mind Deficits and Their Influence on Functional Impairment in Remitted Phase of Bipolar Disorder.

Background:Functional impairment has been convincingly established in the euthymic/ remitted phase of bipolar disorder (BD). Though deficits in social cognition, especially theory of mind (ToM), predict functional impairment, the association has not been consistently proven.Methods:Thirty remitted subjects with BD (as per DSM 5) and 30 age- and gender-matched healthy controls were screened for eligibility and the sociodemographic details and ToM scores, that is, first-order ToM, second-order ToM, and Faux pas, were collected. In subjects with BD, functioning was assessed using Functioning Assessment Short Test (FAST) and illness variables were collected.Results:No significant difference was found in occupation or education between the groups. Remitted subjects with BD had statistically significant deficits in all domains of ToM, that is, first-order ToM (r = 0.65), second-order ToM (r = 0.69), and Faux pas (r = 0.75). Significant correlations existed between first-order ToM and FAST total score, as well as second-order ToM and FAST total score, but the correlations dropped after controlling for duration of illness and number of depressive episodes. Quantile regression analysis showed that the only factors which predicted global functional impairment was a higher number of episodes (βτ= –0.45, SE = 3.51, t = 0.13, P = 0.04), while all other illness variables and ToM failed to predict the global functioning.Conclusion:Though there seems to be an association between ToM and functioning, only illness variables predicted functional impairment in subjects with BD. We need prospective studies to delineate the contributors to functional impairment.

Insula and Amygdala Atrophy Are Associated With Functional Impairment in Subjects With Presbycusis.

Hearing loss is an important risk factor for dementia. However, the mechanisms that relate these disorders are still unknown. As a proxy of this relationship, we studied the structural brain changes associated with functional impairment in activities of daily living in subjects with age related hearing loss, or presbycusis. One hundred eleven independent, non-demented subjects older than 65 years recruited in the ANDES cohort were evaluated using a combined approach including (i) audiological tests: hearing thresholds and cochlear function measured by pure tone averages and the distortion product otoacoustic emissions respectively; (ii) behavioral variables: cognitive, neuropsychiatric, and functional impairment in activities of daily living measured by validated questionnaires; and (iii) structural brain imaging—assessed by magnetic resonance imaging at 3 Tesla. The mean age of the recruited subjects (69 females) was 73.95 ± 5.47 years (mean ± SD) with an average educational level of 9.44 ± 4.2 years of schooling. According to the audiometric hearing thresholds and presence of otoacoustic emissions, we studied three groups: controls with normal hearing (n = 36), presbycusis with preserved cochlear function (n = 33), and presbycusis with cochlear dysfunction (n = 38). We found a significant association (R2D = 0.17) between the number of detected otoacoustic emissions and apathy symptoms. The presbycusis with cochlear dysfunction group had worse performance than controls in global cognition, language and executive functions, and severe apathy symptoms than the other groups. The neuropsychiatric symptoms and language deficits were the main determinants of functional impairment in both groups of subjects with presbycusis. Atrophy of insula, amygdala, and other temporal areas were related with functional impairment, apathy, and language deficits in the presbycusis with cochlear dysfunction group. We conclude that (i) the neuropsychiatric symptoms had a major effect on functional loss in subjects with presbycusis, (ii) cochlear dysfunction is relevant for the association between hearing loss and behavioral impairment, and (iii) atrophy of the insula and amygdala among other temporal areas are related with hearing loss and behavioral impairment.

Assessment of Functional Impairments in Male Children and Adolescents with Attention-Deficit/Hyperactivity Disorder and Oppositional Defiant Disorder

Objectives Many studies have demonstrated comorbidities and overlapping symptoms in attention- deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD). The purpose of this study was to examine the functional impairment in subjects with ADHD, ODD, and in those with both ADHD and ODD. Methods 172 male subjects, aged 6 to 15 years old, were enrolled in this study. Based on diagnoses made by applying the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime (K-SADS-PL), the subjects were categorized into four groups: ADHD group (n=64), ODD group (n=17), ADHD+ODD group (n=28), and control group (n=63). The Child and Adolescent Functioning Impairment Scale (CAFIS) was used to measure the functional impairment of the subjects. CAFIS consists of four subscales : Family relationship, Teacher relationship, Peer relationship, and Academic achievement scales. A high CAFIS score implies high functional impairment. Analysis of covariance was conducted to compare the scores between the four groups. Results Both the ODD and the ADHD+ODD groups had significantly high scores for Parent relationship compared to that of the ADHD group. Compared to the control group, both the ADHD and the ADHD+ODD group had significantly higher scores for Peer relationship and Academic achievement, whereas, the ODD group showed no significant difference from the control group on those two subscales. Conclusion The present study showed that subjects with ADHD and ODD have different functional impairment characteristics. The subjects’ relationships with their parents were worsened by the presence of ODD. Peer relationships and Academic achievements were significantly affected by the presence of ADHD.

Trait Anxiety as a Mediator of the Association between Attention Deficit Hyperactivity Disorder Symptom Severity and Functional Impairment.

ObjectiveAnxiety has been shown to influence functional impairment in patients with attention deficit hyperactivity disorder (ADHD). This study aimed to compare functional impairment in subjects with and without adult ADHD and to investigate the associations among trait anxiety, functional impairment, and ADHD symptom severity. Moreover, the effects of ADHD symptom subtypes on trait anxiety and functional impairment were also examined.MethodsThe sample included 209 adults between the ages of 20 and 31 years. Fifty-one adults received a diagnosis of ADHD, and an additional age, sex-matched group of 51 adults comprised the adult control. Participants were assessed with Conners’ Adult ADHD Rating Scales (CAARS), the Beck Depression Inventory (BDI), the Spielberg Trait Anxiety Inventory (STAI-T), and the Sheehan Disability Scale (SDS). The relationships among ADHD severity, anxiety, and functional impairment were investigated using Pearson’s correlation analysis. Subtypes of ADHD symptoms that predicted anxiety and functional impairment were investigated using regression analyses.ResultsAdult ADHD patients significantly differed from normal control subjects according to BDI, STAI-T, and SDS assessment. Significant positive correlations were noted between ADHD severity, anxiety, and functional impairment. Multiple linear regression analysis confirmed anxiety as a mediator between functional impairment and ADHD CAARS symptom subscales.ConclusionPatients with adult ADHD showed higher levels of anxiety, depression, and functional impairment. Additionally, ADHD symptoms and anxiety impacted subject functional impairment. Our results suggest that anxiety may be a strong mediator between ADHD severity and functional impairment.

Inflammatory cytokines and functional impairment in drug-free subjects with mood disorder

ObjectiveTo assess the association between peripheral levels of inflammatory cytokines and functional impairment in subjects with Bipolar Disorder (BD), Major Depressive Disorder (MDD) and population controls. MethodsThis was a cross-sectional study with a matched sample of drug-free young adults with BD (n=48), MDD (n=48) and population controls (n=48). Mood disorder was confirmed by a certified psychologist using the Structured Clinical Interview for DSM-IV (SCID-I). Functional impairment was assessed using the Functional Assessment Short Test (FAST). Serum levels of IL-6 and IL-10 were measured by ELISA. ResultsPeripheral levels of IL-6 and IL-10 were not significantly different between subjects with BD, MDD compared to controls. Higher levels of functional impairment were verified in subjects with BD and MDD compared to population controls (p≤0.001). In addition, IL-6 and IL-10 levels were positively correlated with functional impairment in subjects with BD (IL-6: r=0.349, p=0.016; and IL-10: r=0.351, p=0.016). ConclusionInflammatory dysregulation was associated with functional impairment among drug-free subjects with BD. This finding suggests that inflammatory dysregulation may be involved in the neuroprogression of BD.

Emphysema and Airflow Obstruction in Non-Smoking Coal Miners with Pneumoconiosis.

BackgroundAccumulating evidence shows that functional impairment in subjects with coal workers’ pneumoconiosis (CWP) is principally due to emphysema and airflow obstruction, rather than underlying restrictive mechanisms. However, cigarette smoking has remained a major confounder. The aim of this study was to assess whether coal dust exposure was associated with emphysema and/or airflow obstruction in the absence of smoking history.Material/MethodThe subjects evaluated for possible pneumoconiosis between 2013 and 2015 were retrospectively enrolled into this study. After excluding those with history of smoking, tuberculosis, or lung cancer, the study population was a total of 57 subjects. The emphysema severity and airflow obstruction were quantified by computed tomographic densitometry analysis and spirometry, respectively. For comparability regarding emphysema, 9 age- and sex-matched nonsmoker (n=9) control subjects without known lung disease were randomly selected from a radiology database.ResultsEmphysema severity was significantly higher in the CWP group compared with the control group (15% vs. 4%, p<0.001). The median percent emphysema and percentage of those with FEV1/FVC <0.7 was 13% and 37% in subjects with simple CWP and 18% and 67% in subjects with complicated CWP, respectively. Percent emphysema and Perc15 (15th percentile of the attenuation curve) was correlated with FEV1/FVC (r=−0.45, r=−0.47) and FEF25–75 (r=−0.36, r=−0.56), respectively, but not with perfusion score. A linear regression analysis showed that factors associated with emphysema were FEV1/FVC (β=−0.24, p=0.009) and large opacity (β=−3.97, p=0.079), and factors associated with FEV1/FVC were percent emphysema (β=−0.51, p=0.018) and tenure (β=−0.63, p=0.044).ConclusionsOur results support the observation that coal dust exposure is associated with emphysema and airflow obstruction, independent of smoking status.

Longitudinal beta-binomial modeling using GEE for overdispersed binomial data.

Longitudinal binomial data are frequently generated from multiple questionnaires and assessments in various scientific settings for which the binomial data are often overdispersed. The standard generalized linear mixed effects model may result in severe underestimation of standard errors of estimated regression parameters in such cases and hence potentially bias the statistical inference. In this paper, we propose a longitudinal beta-binomial model for overdispersed binomial data and estimate the regression parameters under a probit model using the generalized estimating equation method. A hybrid algorithm of the Fisher scoring and the method of moments is implemented for computing the method. Extensive simulation studies are conducted to justify the validity of the proposed method. Finally, the proposed method is applied to analyze functional impairment in subjects who are at risk of Huntington disease from a multisite observational study of prodromal Huntington disease. Copyright © 2016 John Wiley & Sons, Ltd.

Validation and Use of the Functioning Assessment Short Test in First Psychotic Episodes

Numerous studies have documented high rates of functional impairment in patients with schizophrenia and bipolar disorder. However, this impairment appears early in the course of the illness. The purpose of the present study was to validate the Functioning Assessment Short Test (FAST) by comparing it with the Strauss-Carpenter Scale for use as an instrument to assess functional impairment in subjects with first psychotic episodes. The study was conducted on 53 patients admitted to Santiago Apostol Hospital because of a first psychotic episode. The FAST showed high internal consistency both at baseline and at 6 months as well as at 1 year. Concurrent validity showed a highly significant negative correlation at each time point. The FAST also showed good reliability and discriminant validity. The FAST showed strong psychometric properties and is a valid instrument for use in clinical practice, clinical trials, and research settings in subjects with first psychotic episodes.

A gel-based method for purification of apolipoprotein A-I from small volumes of plasma

We present here a gel-based method for rapid purification of apolipoprotein A-I (apoA-I) from small volumes of human plasma. After isolation of high density lipoprotein from plasma, the apoA-I protein was separated by electrophoresis and the apoA-I band excised from the gel. The apoA-I was then eluted from the gel strip, concentrated, and delipidated ready for use. The structure and function of the gel-purified apoA-I protein was compared against apoA-I purified by the traditional size-exclusion chromatography method. The α-helical content of the gel-purified apoA-I as determined by circular dichroism was similar to chromatography-purified apoA-I. The functional activity of gel-purified apoA-I, as determined by cholesterol efflux assays in primary human fibroblasts and RAW264.7 macrophages, was also comparable with chromatography-purified apoA-I. This method is a valid alternative for apoA-I purification with some advantages over traditional chromatography purification including a much reduced plasma volume requirement, less time and cost, and a higher percentage protein recovery. The method is particularly suitable for applications requiring the purification of apoA-I from multiple human or animal samples of interest.

HDL, lipid peroxidation, and atherosclerosis

Genetic, clinical, and pharmacological studies implicate elevated levels of LDL in the pathogenesis of atherosclerotic vascular disease, the leading cause of death in industrialized societies (1). Paradoxically, native LDL fails to exert potentially atherogenic effects in vitro, suggesting that it must be modified to promote vascular disease. Indeed, many lines of evidence support the LDL oxidation hypothesis, which suggests that oxidative damage to LDL is one important mechanism for rendering lipoproteins atherogenic (as reviewed in Refs. 2, 3).

A sensitive and specific ELISA detects methionine sulfoxide-containing apolipoprotein A-I in HDL

Oxidized HDL has been proposed to play a key role in atherogenesis. A wide range of reactive intermediates oxidizes methionine residues to methionine sulfoxide (MetO) in apolipoprotein A-I (apoA-I), the major HDL protein. These reactive species include those produced by myeloperoxidase, an enzyme implicated in atherogenesis. The aim of the present study was to develop a sensitive and specific ELISA for detecting MetO residues in HDL. We therefore immunized mice with HPLC-purified human apoA-I containing MetO(86) and MetO(112) (termed apoA-I(+32)) to generate a monoclonal antibody termed MOA-I. An ELISA using MOA-I detected lipid-free apoA-I(+32), apoA-I modified by 2e-oxidants (hydrogen peroxide, hypochlorous acid, peroxynitrite), and HDL oxidized by 1e- or 2e-oxidants and present in buffer or human plasma. Detection was concentration dependent, reproducible, and exhibited a linear response over a physiologically plausible range of concentrations of oxidized HDL. In contrast, MOA-I failed to recognize native apoA-I, native apoA-II, apoA-I modified by hydroxyl radical or metal ions, or LDL and methionine-containing proteins other than apoA-I modified by 2e-oxidants. Because the ELISA we have developed specifically detects apoA-I containing MetO in HDL and plasma, it should provide a useful tool for investigating the relationship between oxidized HDL and coronary artery disease.

Apolipoprotein A-I is a selective target for myeloperoxidase-catalyzed oxidation and functional impairment in subjects with cardiovascular disease

In recent studies we demonstrated that systemic levels of protein-bound nitrotyrosine (NO2Tyr) and myeloperoxidase (MPO), a protein that catalyzes generation of nitrating oxidants, serve as independent predictors of atherosclerotic risk, burden, and incident cardiac events. We now show both that apolipoprotein A-I (apoA-I), the primary protein constituent of HDL, is a selective target for MPO-catalyzed nitration and chlorination in vivo and that MPO-catalyzed oxidation of HDL and apoA-I results in selective inhibition in ABCA1-dependent cholesterol efflux from macrophages. Dramatic selective enrichment in NO2Tyr and chlorotyrosine (ClTyr) content within apoA-I recovered from serum and human atherosclerotic lesions is noted, and analysis of serum from sequential subjects demonstrates that the NO2Tyr and ClTyr contents of apoA-I are markedly higher in individuals with cardiovascular disease (CVD). Analysis of circulating HDL further reveals that higher NO2Tyr and ClTyr contents of the lipoprotein are each significantly associated with diminished ABCA1-dependent cholesterol efflux capacity of the lipoprotein. MPO as a likely mechanism for oxidative modification of apoA-I in vivo is apparently facilitated by MPO binding to apoA-I, as revealed by cross-immunoprecipitation studies in plasma, recovery of MPO within HDL-like particles isolated from human atheroma, and identification of a probable contact site between the apoA-I moiety of HDL and MPO. To our knowledge, the present results provide the first direct evidence for apoA-I as a selective target for MPO-catalyzed oxidative modification in human atheroma. They also suggest a potential mechanism for MPO-dependent generation of a proatherogenic dysfunctional form of HDL in vivo.

Evaluation of communicative and functional abilities in Wolf–Hirshhorn syndrome

Wolf-Hirschhorn syndrome (WHS) is a genetic condition characterized by many clinical disorders, learning difficulties, dysphagia, neuromotor deficits and communicative deficits. Up until now, no studies in the literature have described the development of communicative and functional abilities in subjects with WHS. In the present study of 11 patients with WHS, a descriptive analysis was made of several abilities and three groups of patients were identified on the basis of the severity of their functional deficit. A non-homogeneous picture of impairment emerged in various areas of development. Overall, the neuromotor abilities of these patients were more adequate than their abilities related to autonomy in personal life, alimentary function, and cognitive and communicative-linguistic aspects. Based on the identification of specific patterns of communicative and functional impairment in subjects with WHS, rehabilitative intervention strategies can be planned to increase their communicative opportunities, and possibilities for active and autonomous participation in various life contexts (e.g. home, school and the social environment).

High-Density Lipoprotein and the Dynamics of Atherosclerotic Lesions

Plump et al1 reported in 1994 that the expression of a human transgene for apoA-I, the major apolipoprotein of HDL, in apoE knockout mice dramatically reduced lesion formation. In the present issue of Circulation , Rong et al2 demonstrate that the composition and structure of advanced atherosclerotic plaques can be significantly altered by the expression of this same transgene. Rong and colleagues2 used a novel transplant model. They fed apoE knockout mice a Western diet for 6 months to generate advanced lesions. Subsequently, they surgically removed portions of the aorta from these mice and transplanted them into the aortas of syngeneic mice on a chow diet, some of which also expressed the transgene for human apoA-I. The recipient mice expressing the human transgene had ≈2.5-fold higher HDL cholesterol levels and expressed 130±15 mg/dL of human apoA-I. The non-HDL cholesterol levels were approximately half of those that had been present in the donor mice and were similar, regardless of whether the transgene was expressed or not. Five months later, despite non-HDL cholesterol levels that were half those of the donor mice, there was progression in the transplanted lesions, although there was less progression in the mice expressing the human apoA-I transgene. However, the characteristics of the lesions were dramatically different. The recipients expressing the transgene had a >80% decrease in lesion macrophage area and a >300% increase in smooth muscle cell content, with most of the changes occurring in the superficial subendothelial layer. See p 2447 In another study, Reis et al3 found that transplanting aortic segments from apoE knockout mice on a Western diet with advanced lesions into the aortas of …

Altered fractal dynamics of gait: reduced stride-interval correlations with aging and Huntington's disease.

Fluctuations in the duration of the gait cycle (the stride interval) display fractal dynamics and long-range correlations in healthy young adults. We hypothesized that these stride-interval correlations would be altered by changes in neurological function associated with aging and certain disease states. To test this hypothesis, we compared the stride-interval time series of 1) healthy elderly subjects and young controls and of 2) subjects with Huntington's disease and healthy controls. Using detrended fluctuation analysis we computed alpha, a measure of the degree to which one stride interval is correlated with previous and subsequent intervals over different time scales. The scaling exponent alpha was significantly lower in elderly subjects compared with young subjects (elderly: 0.68 +/- 0.14; young: 0.87 +/- 0.15; P < 0.003). The scaling exponent alpha was also smaller in the subjects with Huntington's disease compared with disease-free controls (Huntington's disease: 0.60 +/- 0.24; controls: 0.88 +/-0.17; P < 0.005). Moreover, alpha was linearly related to degree of functional impairment in subjects with Huntington's disease (r = 0.78, P < 0.0005). These findings demonstrate that strike-interval fluctuations are more random (i.e., less correlated) in elderly subjects and in subjects with Huntington's disease. Abnormal alterations in the fractal properties of gait dynamics are apparently associated with changes in central nervous system control.

Influence of amyl nitrite inhalation on the systolic time intervals in normal subjects and in patients with ischemic heart disease.

The systolic time intervals of the left ventricle in 30 patients with ischemic heart disease but without heart failure were compared with those of 30 normal individuals before and after inhalation of amyl nitrite by using polygraphic recordings. In the normal subjects, following amyl nitrite, the ejection-time index was significantly prolonged, and the pre-ejection period and its index were significantly reduced, while the ejection time was not significantly shortened. The ischemic heart disease group, however, exhibited no significant changes in the ejection-time index, pre-ejection period, or its index, whereas the ejection time was significantly shortened. These differences were not related to heart rate or diastolic blood pressure level but may be explained by a postulated lack of increase in stroke volume or in the contractility of the ischemic myocardium, or both, at the maximal effect of amyl nitrite. The responses of the left ventricular systolic intervals to amyl nitrite may prove useful as a clinical test of latent ventricular functional impairment in subjects with ischemic heart disease.