Evolution and treatment of vitamin B12 deficiency as a risk factor for (cognitive and functional) neurodegenerative diseases in institutionalized elderly = Evolución y tratamiento de la deficiencia de vitamina B12 como factor de riesgo de enfermedades neurodegenerativas (cognitivas y funcionales) en las personas mayores institucionalizadas.

Prevalence of vitamin B12 deficiency is very common in elderly people and can reach values as high as 40.5% of the population. It can be the result of the interaction among several factors. Vitamin B12 deficiencies have been associated with neurological, cognitive deterioration, haematological abnormalities and cardiovascular diseases that have an important influence on the health of the elderly and their quality of life. It is necessary to approach the problems arisen from the lack of data relative to them. The main objective of this thesis was to analyse the evolution of vitamin B12 status and related parameters, lipid and haematological profiles and their relationship to health risk factors, and to functional and cognitive status over one year and to determine the effect of an oral supplementation of 500 μg of cyanocobalamin for a short period of 28 days. An additional objective was to analyze the possible effects of medicine intakes on vitamin B status. Three studies were performed: a) a one year longitudinal follow-up with four measure points; b) an intervention study providing an oral liquid supplement of 500 μg of cyanocobalamin for a 28 days period; and c) analysis of the possible effect of medication intake on vitamin B status using the ATC classification of medicines. The participants for these studies were recruited from nursing homes for the elderly in the Region of Madrid. Sixty elders (mean age 84 _ 7y, 19 men and 41 women) were recruited for Study I and 64 elders (mean age 82 _ 7y, 24 men and 40 women) for Study II. For Study III, baseline data from the initially recruited participants of the first two studies were used. An informed consent was obtained from all participants or their mentors. The studies were approved by the Ethical Committee of the University of Granada. Blood samples were obtained at each examination date and were analyzed for serum cobalamin, holoTC, serum and RBC folate and total homocysteine according to laboratory standard procedures. The haematological parameters analyzed were haematocrit, haemoglobin and MCV. For the lipid profile TG, total cholesterol, LDL- and HDLcholesterol were analyzed. Anthropometric measures (BMI, skinfolds [triceps and subscapular], waist girth and waist to hip ratio), functional tests (hand grip, arm and leg strength tests, static balance) and MMSE were obtained or administered by trained personal. The vitamin B12 supplement of Study II was administered with breakfast and the medication intake was taken from the residents’ anamnesis. Data were analyzed by parametric and non-parametric statistics depending on the obtained data. Comparisons were done using the appropriate ANOVAs or non-parametric tests. Pearsons’ partial correlations with the variable “time” as control were used to define the association of the analyzed parameters. XIII The results showed that: A) Over one year, in relationship to vitamin B status, serum cobalamin decreased, serum folate and mean corpuscular volumen increased significantly and total homocysteine concentrations were stable. Regarding blood lipid profile, triglycerides increased and HDL-cholesterol decreased significantly. Regarding selected anthropometric measurements, waist circumference increased significantly. No significant changes were observed for the rest of parameters. B) Prevalence of hyperhomocysteinemia was high in the elderly studied, ranging from 60% to 90 % over the year depending on the cut-off used for the classification. LDL-cholesterol values were high, especially among women, and showed a tendency to increase over the year. Results of the balance test showed a deficiency and a tendency to decrease; this indicates that the population studied is at high risk for falls. Lower extremity muscular function was deficient and showed a tendency to decrease. A highly significant relationship was observed between the skinfold of the triceps and blood lipid profile. C) Low cobalamin concentrations correlated significantly with low MMSE scores in the elderly studied. No correlations were observed between vitamin B12 status and functional parameters. D) Regarding vitamin B12 status, holo-transcobalamin seems to be more sensitive for diagnosis; 5-10% of the elderly had a deficiency using serum cobalamin as a criterion, and 45-52% had a deficiency when using serum holotranscobalamin as a criterion. E) 500 μg of cyanocobalamin administered orally during 28 days significantly improved vitamin B12 status and significantly decreased total homocysteine concentrations in institutionalized elderly. No effect of the intervention was observed on functional and cognitive parameters. F) The relative change (%) of improvement of vitamin B12 status was higher when using serum holo-transcobalamin as a criterion than serum cobalamin. G) Antiaenemic drug intake normalized cobalamin, urologic drugs and corticosteroids serum folate, and psychoanaleptics holo-transcobalamin levels. Drugs treating pulmonary obstruction increased total homocysteine concentration significantly. H) The daily mean drug intake was 5.1. Fiftynine percent of the elderly took medication belonging to 5 or more different ATC groups. The most prevalent were psycholeptic (53%), antiacid (53%) and antithrombotic (47%) drugs.

Reliability and Validity Evidence of Scores on the French Version of the Questionnaire about Interpersonal Difficulties for Adolescents

This study examined the reliability and validity evidence drawn from the scores of the French version of the Questionnaire about Interpersonal Difficulties for Adolescents (QIDA) in a sample of 957 adolescents (48.5% boys) ranging in age from 11 to 18 years (M = 14.48, SD = 1.85). A principal axis factoring (PAF) and confirmatory factor analyses (CFA) were performed to determine the fit of the factor structure of scores on the QIDA. PAF and CFA replicated the previously identified correlated five-factor structure of the QIDA: Assertiveness, Heterosexual Relationships, Public Speaking, Family Relationships, and Close Friendships. The QIDA yielded acceptable reliability scores for French adolescents. Validity evidence of QIDA was also established through correlations with scores on the School Anxiety Inventory and the Social Anxiety Scale for Adolescents. Most of the correlations were positive and exceeded the established criteria of statistical significance, but the magnitude of these varied according to the scales of the QIDA. Results supported the reliability and validity evidence drawn from the scores of the French version of the QIDA.

Phobic anxiety in 11 nations: Part I: Dimensional constancy of the five-factor model

The Fear Survey Schedule-III (FSS-III) was administered to a total of 5491 students in Australia, East Germany, Great Britain, Greece, Guatemala, Hungary, Italy, Japan, Spain, Sweden, and Venezuela, and submitted to the multiple group method of confirmatory analysis (MGM) in order to determine the cross-national dimensional constancy of the five-factor model of self-assessed fears originally established in Dutch, British, and Canadian samples. The model comprises fears of bodily injury-illness-death, agoraphobic fears, social fears, fears of sexual and aggressive scenes, and harmless animals fears. Close correspondence between the factors was demonstrated across national samples. In each country, the corresponding scales were internally consistent, were intercorrelated at magnitudes comparable to those yielded in the original samples, and yielded (in 93% of the total number of 55 comparisons) sex differences in line with the usual finding (higher scores for females). In each country, the relatively largest sex differences were obtained on harmless animals fears. The organization of self-assessed fears is sufficiently similar across nations to warrant the use of the same weight matrix (scoring key) for the FSS-III in the different countries and to make cross-national comparisons feasible. This opens the way to further studies that attempt to predict (on an a priori basis) cross-national variations in fear levels with dimensions of national cultures. (C) 2002 Elsevier Science Ltd. All rights reserved.

A genetic investigation of the covariation among Inspection Time, Choice Reaction Time, and IQ subtest scores

Information processing speed, as measured by elementary cognitive tasks, is correlated with higher order cognitive ability so that increased speed relates to improved cognitive performance. The question of whether the genetic variation in Inspection Time (IT) and Choice Reaction Time (CRT) is associated with IQ through a unitary factor was addressed in this multivariate genetic study of IT, CRT, and IQ subtest scores. The sample included 184 MZ and 206 DZ twin pairs with a mean age of 16.2 years (range 15-18 years). They were administered a visual (pi-figure) IT task, a two-choice RT task, five computerized subtests of the Multidimensional Aptitude Battery, and the digit symbol substitution subtest from the WAIS-R. The data supported a factor model comprising a general, three group (verbal ability, visuospatial ability, broad speediness), and specific genetic factor structure, a shared environmental factor influencing all tests but IT, plus unique environmental factors that were largely specific to individual measures. The general genetic factor displayed factor loadings ranging between 0.35 and 0.66 for the IQ subtests, with IT and CRT loadings of -0.47 and -0.24, respectively. Results indicate that a unitary factor is insufficient to describe the entire relationship between cognitive speed measures and all IQ subtests, with independent genetic effects explaining further covariation between processing speed (especially CRT) and Digit Symbol.

Transcultural properties of the Composite Scale of Morningness: The relevance of the "morning affect" factor

Morningness scales have been translated into several languages, but it lack of normative data and methodological differences make cross-cultural comparisons difficult. This study examines the psychometric properties and factor structure of the Composite Scale of Morningness (CSM) in samples from five countries: France (n = 627), Italy (n, = 702), Spain (n = 391), Thailand (n. = 503), and Australia (17 = 654). Strong national differences are identified. A quadratic relationship between age and CSM total score was apparent in the Australian data with a downward trend after age 35 yrs. There was no age effect in air), sample in the range from 18 to 29 yrs. Factor analysis identified a three-factor solution in all groups for both men and women. Tucker's congruence coefficients indicate that: (1) this solution is highly congruent between sexes in each culture, and (2) a morning affect factor is highly congruent between cultures. These results indicate there are national differences in factorial structure and that cut-off scores used to categorize participants as morning- and evening-types should be established for different cultural and age groups.

Increased potency of a novel complement factor 5a receptor antagonist in a rat model of inflammatory bowel disease

We have previously shown that complement factor 5a(C5a) plays a role in the pathogenesis of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats by using the selective, orally active C5a antagonist AcF-[OP(D-Cha) WR]. This study tested the efficacy and potency of a new C5a antagonist, hydrocinnamate (HC)-[OP(D-Cha) WR], which has limited intestinal lumenal metabolism, in this model of colitis. Analogs of AcF-[OP(D-Cha) WR] were examined for their susceptibility to alimentary metabolism in the rat using intestinal mucosal washings. One metabolically stable analog, HC-[OP(D-Cha)WR], was then evaluated pharmacokinetically and investigated at a range of doses (0.03 - 10 mg/kg/ day p.o.) in the 8-day rat TNBS- colitis model, against the comparator drug AcF-[OP(D-Cha) WR]. Using various amino acid substitutions, it was determined that the AcF moiety of AcF-[OP(D-Cha) WR] was responsible for the metabolic instability of the compound in intestinal mucosal washings. The analog HC-[OP( D-Cha) WR], equiactive in vitro to AcF-[OP(D-Cha) WR], was resistant to intestinal metabolism, but it displayed similar oral bioavailability to AcF-[OP(D-Cha) WR]. However, in the rat TNBS- colitis model, HC-[OP(D-Cha) WR] was effective at reducing mortality, colon edema, colon macroscopic scores, and increasing food consumption and body weights, at 10- to 30- fold lower oral doses than AcF-[OP( D-Cha) WR]. These studies suggest that resistance to intestinal metabolism by HC-[OP(D-Cha) WR] may result in increased local concentrations of the drug in the colon, thus affording efficacy with markedly lower oral doses than AcF-[OP(D-Cha) WR] against TNBS-colitis. This large increase in potency and high efficacy of this compound makes it a potential candidate for clinical development against intestinal diseases such as inflammatory bowel disease.

Factor structure and internal consistency of the Young Schema Questionnaire (Short Form) in Korean and Australian samples

We investigated cross-cultural differences in the factor structure and psychometric properties of the 75-item Young Schema Questionnaire-Short Form (YSQ-SF). Participants were 833 South Korean and 271 Australian undergraduate students. The South Korean sample was randomly divided into two sub-samples. Sample A was used for Exploratory Factor Analysis (EFA) and sample B was used for Confirmatory Factor Analysis (CFA). EFA for the South Korean sample revealed a 13-factor solution to be the best fit for the data, and CFA on the data from sample B confirmed this result. CFA on the data from the Australian sample also revealed a 13-factor solution. The overall scale of the YSQ-SF demonstrated a high level of internal consistency in the South Korean and Australian groups. Furthermore, adequate internal consistencies for all subscales in the South Korean and Australian samples were demonstrated. In conclusion, the results showed that YSQ-SF with 13 factors has good psychometric properties and reliability for South Korean and Australian University students. Korean samples had significantly higher YSD scores on most of the 13 subscales than the Australian sample. However, limitations of the current study preclude the generalisability of the findings to beyond undergraduate student populations. (c) 2006 Elsevier B.V. All rights reserved.

Assessing the quality of risk factor survey data: lessons from the WHO MONICA Project

Background and purpose Survey data quality is a combination of the representativeness of the sample, the accuracy and precision of measurements, data processing and management with several subcomponents in each. The purpose of this paper is to show how, in the final risk factor surveys of the WHO MONICA Project, information on data quality were obtained, quantified, and used in the analysis. Methods and results In the WHO MONICA (Multinational MONItoring of trends and determinants in CArdiovascular disease) Project, the information about the data quality components was documented in retrospective quality assessment reports. On the basis of the documented information and the survey data, the quality of each data component was assessed and summarized using quality scores. The quality scores were used in sensitivity testing of the results both by excluding populations with low quality scores and by weighting the data by its quality scores. Conclusions Detailed documentation of all survey procedures with standardized protocols, training, and quality control are steps towards optimizing data quality. Quantifying data quality is a further step. Methods used in the WHO MONICA Project could be adopted to improve quality in other health surveys.

Cross-cultural confirmatory factor analysis of the CES-D in Spanish and Mexican dementia caregivers

The Center for Epidemiologic Studies-Depression Scale (CES-D) is the most frequently used scale for measuring depressive symptomatology in caregiving research. The aim of this study is to test its construct structure and measurement equivalence between caregivers from two Spanish-speaking countries. Face-to-face interviews were carried out with 595 female dementia caregivers from Madrid, Spain, and from Coahuila, Mexico. The structure of the CES-D was analyzed using exploratory and confirmatory factor analysis (EFA and CFA, respectively). Measurement invariance across samples was analyzed comparing a baseline model with a more restrictive model. Significant differences between means were found for 7 items. The results of the EFA clearly supported a four-factor solution. The CFA for the whole sample with the four factors revealed high and statistically significant loading coefficients for all items (except item number 4). When equality constraints were imposed to test for the invariance between countries, the change in chi-square was significant, indicating that complete invariance could not be assumed. Significant between-countries differences were found for three of the four latent factor mean scores. Although the results provide general support for the original four-factor structure, caution should be exercised on reporting comparisons of depression scores between Spanish-speaking countries.

Peripheral brain-derived neurotrophic factor levels in alzheimer's disease and mild cognitive impairment: A comprehensive systematic review and meta-analysis

Alzheimer's disease (AD) is becoming a growing global problem, and there is an urgent need to identify reliable blood biomarkers of the risk and progression of this condition. A potential candidate is the brain-derived neurotrophic factor (BDNF), which modulates major trophic effects in the brain. However, findings are apparently inconsistent regarding peripheral blood BDNF levels in AD patients vs. healthy people. We thus performed a systematic review and meta-analysis of the studies that have examined peripheral BDNF levels in patients with AD or mild cognitive impairment (MCI) and healthy controls. We searched articles through PubMed, EMBASE, and hand searching. Over a total pool of 2061 potential articles, 26 met all inclusion criteria (including a total of 1584 AD patients, 556 MCI patients, and 1294 controls). A meta-analysis of BDNF levels between early AD and controls showed statistically significantly higher levels (SMD [95 % CI]: 0.72 [0.31, 1.13]) with no heterogeneity. AD patients with a low (<20) mini-mental state examination (MMSE) score had lower peripheral BDNF levels compared with controls (SMD [95 % CI]: -0.33 [-0.60, -0.05]). However, we found no statistically significant difference in blood (serum/plasma) BDNF levels between all AD patients and controls (standard mean difference, SMD [95 % CI]: -0.16 [-0.4, 0.07]), and there was heterogeneity among studies (P < 0.0001, I 2 = 85.8 %). There were no differences in blood BDNF levels among AD or MCI patients vs. controls by subgroup analyses according to age, sex, and drug use. In conclusion, this meta-analysis shows that peripheral blood BDNF levels seem to be increased in early AD and decreased in AD patients with low MMSE scores respectively compared with their age- and sex-matched healthy referents. At present, however, this could not be concluded from individual studies.

Quinn’s Leadership Roles: A Confirmatory Factor Analysis Study in Portuguese Health Services

Purpose: To evaluate psychometric properties of Quinn’s leadership questionnaire (CFV questionnaire; 1988) to the Portuguese health services. Design: Cross-sectional study, using the Quinn’s leadership questionnaire, administered to registered nurses and physicians in Portuguese health care services (N = 687). Method: Self-administered survey applied to two samples. In the first (of convenience; N = 249 Portuguese health professionals) were performed exploratory factor and reliability analysis to the CFV questionnaire. In the second sample (stratified; N = 50 surgical units of 33 Portuguese hospitals) was performed confirmatory factor analysis using LISREL 8.80. Findings: The first sample supported an eight-factor solution accounting for 65.46% of the variance, in an interpretable factorial structure (loadings> .50), with Cronbach’s α upper than .79. This factorial structure, replicated with the second sample, showed reasonable fit for each of the 8 leadership roles, quadrants, and global model. The models evidenced, generally, nomological validity, with scores between good and acceptable (.235 < x2/df < 2.055 e .00 < RMSEA < .077). Conclusions: Quinn’s leadership questionnaire presented good reliability and validity for the eight leadership roles, showing to be suitable for use in hospital health care context. Key-Words: Leadership; Quinn’s CVF questionnaire; health services; Quinn’s competing values.