Establishing conversion of the 16-item Informant Questionnaire on Cognitive Decline in the Elderly scores into interval-level data across multiple samples using Rasch methodology

Background

The 16-item Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE-16) is a well-validated and widely-used measure of cognitive changes (CCs) among older adults. This study aimed to use Rasch methodology to establish psychometric properties of the IQCODE-16 and validate the existing ordinal-to-interval transformation algorithms across multiple large samples.

Methods

A Partial Credit Rasch model was employed to examine psychometric properties of the IQCODE-16 using data (n = 918) from two longitudinal studies of participants aged 57–99 years: the Older Australian Twins Study (n = 450) and the Canberra Longitudinal Study (n = 468), and reusing the Sydney Memory and Ageing Study (MAS) sample (n = 400).

Results

Initial analyses indicated good reliability for the IQCODE-16 (Person Separation Index range: 0.82–0.90). However, local dependency was identified between items, with several items showing misfit to the model. Replicating the existing Rasch solution could not reproduce the best Rasch model fit for all samples. Combining locally dependent items into three testlets resolved all misfit and local dependency issues and resulted in the best Rasch model fit for all samples with evidence of unidimensionality, strong reliability, and invariance across person factors. Accordingly, new ordinal-to-interval transformation algorithms were produced to convert the IQCODE-16 ordinal scores into interval data to improve the accuracy of its scores.

Conclusions

The findings of this study support the reliability and validity of the IQCODE-16 in measuring CCs among older adults. New ordinal-to-interval conversion tables generated using samples from multiple independent datasets are more generalizable and can be used to enhance the precision of the IQCODE-16 without changing its original format. An easy-to-use converter has been made available for clinical and research use.     

The lower level of natural anti-thomsen-friedenreich antigen (TFA) agglutinins in sera of patients with gastric cancer related to ABO(H) blood-group phenotype

The TFA is a tumorassociated, bloodgrouprelated glycosidic precursor structure [Gal(β^1-3)GalNAc]. Its expression in carcinomas is accompanied by a decrease of natural TFA antibodies in serum. The relationship between the ABO(H)-bloodgroup phenotype and natural anti-TFA immune response in patients with gastric cancer was studied. The level of TFA agglutinins in the sera of patients with gastric cancer and of healthy controls was examined by the hemagglutination of neuraminidasetreated bloodgroup-O donor erythrocytes. Individuals were classified as weak or strong TFA responders. They were also classified by ABO(H)-bloodgroup status, age, cancer stage, tumor morphology and level of isohemagglutinins. The proportion of weak TFA responders (WR) in cancer patients was 33, 50, 50 and 20% (for O, A, B and AB blood groups respectively), as compared with 11.7, 14.5, 13.9 and 26.1% for bloodgrouprelated controls. The difference between cancer patients and controls was significant for all blood groups except group AB. Further analysis showed agedependence in bloodgroup-O and -B controls, with a high level of WR in the older group. Bloodgroup-A cancer patients had the greatest and uniform suppression of the level of TFA agglutinins, irrespective of age, cancer stage or tumor morphology, and lower levels of anti-B isohemagglutinins. © 1995 Wiley-Liss, Inc.     

Children of alcoholic mothers. Growth and motor performance compared to matched controls

Twenty-one children born 1970-76, selected from 103 children of 30 alcoholic women, were paired to controls matched for sex, age, birth weight and gestational age. The sample (10 girls, 11 boys) was representative of the whole group with regard to weight, length and head circumference at birth. At follow-up (mean age 70 months) the study group was significantly leaner, shorter and had smaller mean head circumference than the control group. The controls had significant catch-up growth from birth to follow-up of weight, height and head circumference to the mean for Swedish children. The study group had no catch-up growth. Compared to controls the study group had significantly lower fine and gross motor age test scores and inferior coordination. One child had cerebral palsy (spastic hemiplegia) and in 6 other children slight tremor and ataxia were observed. Malformations and/or other signs of the fetal alcohol syndrome (FAS) were found in 10 cases. Study group children with FAS had significantly slower growth of head circumference than others without FAS. Children placed in foster home care (n = 11) were found to have significantly (p less than 0.05) lower birth weight, birth length and head circumference than children raised at home (n = 10). There were no significant differences at follow up between study group children raised in foster homes or in homes of their biological mother.     

Insulin treatment of mice recipients preserves beta-cell function in porcine islet transplantation

Encapsulation of islets of Langerhans confers protection against cell-mediated immune destruction and so should allow the transplantation of islets without immunosuppression. Xenotransplantation of encapsulated islets of Langerhans might therefore help overcome problems of human organ donor shortage. Given that islets exposed to sustained hyperglycemia show impaired beta-cell function, we set out to determine whether recipient treatment with insulin could improve transplantation success rate. Islets of Langerhans were obtained from Specific Germ-Free (SPF) pig pancreas and cultured overnight. Islets were encapsulated in AN69 fibers and implanted into the peritoneal cavity of diabetic mice. A group of implanted mice was treated with exogenous insulin from day 3 to day 7 after grafting. Islet implantation depressed plasma glucose in all the mice, both insulin treated and untreated. Glycemia slowly increased in the non-insulin-treated mice, whereas the decrease observed in the insulin-treated mice was maintained until day 29 of follow-up. We found significant differences between the two groups (p < 0.05 at day 18 and day 20, p < 0.001 at day 23 and day 29). No improvement of hyperglycemia was observed in diabetic mice implanted with empty fibers. When islet-containing fibers were removed from the peritoneal cavity of mice 1 month after the graft plasma glucose increased markedly. We demonstrate that treatment of recipients with exogenous insulin in the immediate posttransplantation period has a positive effect on beta-cell function in transplanted macroencapsulated porcine islets.     

The spontaneously hypertensive-rat as an animal model of ADHD: evidence for impulsive and non-impulsive subpopulations

Attention-deficit hyperactivity disorder (ADHD) is a neuropsychiatric syndrome, affecting human infants and adolescents. Two main behavioural features are reported: (1). impaired attention and (2). an impulsive-hyperactive behavioural trait. The latter has been studied in a series of experiments, using the spontaneously hypertensive-rat (SHR) strain (which is regarded as a validated animal model for ADHD) in operant tasks. Food-restricted SHRs and their Wistar-Kyoto (WKY) controls were tested during adolescence (i.e. post-natal days 30-45), in operant chambers provided with two nose-poking holes. Nose-poking in one hole (H1) resulted in the immediate delivery of a small amount of food, whereas nose-poking in the other hole (H5) delivered a larger amount of food after a delay, which was increased progressively each day (0-100 s). As expected, all animals showed a shift in preference from the large (H5) to the immediate (H1) reinforcer as the delay length increased. Impulsivity can be measured by the steepness of this preference-delay curve. The two strains differed in home-cage circadian activity, SHRs being more active than WKYs at several time-points. During the test for impulsivity, inter-individual differences were completely absent in the WKY strain, whereas a huge inter-individual variability was evident for SHRs. On the basis of the median value of average hole-preference, we found an 'impulsive' SHR subgroup, with a very quick shift towards the H1 hole, and a flat-slope ('non-impulsive') SHR subgroup, with little or no shift. The impulsive subpopulation also presented reduced noradrenaline levels in both cingulated and medial-frontal cortex, as well as reduced serotonin turnover in the latter. Also, cannabinoid CB1 receptor density resulted significantly lower in the prefrontal cortex of impulsive SHRs, when compared to both the non-impulsive subgroup and control WKYs. Interestingly, acute administration of a cannabinoid agonist (WIN 55,212, 2 mg/kg s.c.) normalized the impulsive behavioural profile, without any effect on WKY rats. Thus, two distinct subpopulations, differing for impulsive behaviour and specific neurochemical parameters, were evidenced within adolescent SHRs. These results support the notion that a reduced cortical density of cannabinoid CB1 receptors is associated with enhanced impulsivity. This behavioural trait can be positively modulated by administration of a cannabinoid agonist. Present results confirm and extend previous literature, indicating that adolescent SHRs represent a suitable animal model for the preclinical investigation of the early-onset ADHD syndrome.     

Evidence for endogenous agmatine in hypothalamo-neurohypophysial tract and its modulation on vasopressin release and Ca2+ channels

Agmatine, decarboxylated from arginine by arginine decarboxylase, is particularly prominent in the hypothalamus. The present study utilized the rat hypothalamo-neurohypophysial system to determine expression and "pre-synaptic" modulation of agmatine in the central nervous system (CNS). Under confocal-laser scanning, agmatine-like immunoreactivity (Agm-LI) was found enriched in arginine-vasopressin (AVP)-containing magnocellular neurons of the supraoptic nuclei (SON) and paraventricular nuclei (PVN). In addition, using electron microscopy, Agm-LI was found closely associated with large neurosecretory-like vesicles in neurohypophysial nerve terminals of posterior pituitary gland. Radioimmunoassay revealed that 10 and 30 microM agmatine concentration-dependently inhibited the depolarization-evoked AVP release from isolated neurohypophysial terminals. Using perforated patch-clamp, effects of agmatine on whole-terminal voltage-gated ion currents in the isolated neurohypophysial nerve terminals were examined. While it did not significantly affect either tetrodotoxin (TTX)-sensitive Na(+) or sustained Ca(2+)-activated K(+) channel currents, agmatine (1-40 microM) inhibited Ca(2+) channel currents in approximately 53% of the total nerve terminals investigated. The onset of inhibitory effect was immediate, and the inhibition was reversible and concentration-dependent with an IC(50)=4.6 microM. In the remaining (approximately 47%) neurohypophysial nerve terminals, only a higher (120 microM) concentration of agmatine could moderately inhibit Ca(2+) channel currents. The results suggest that: (1) endogenous agmatine is co-expressed in AVP-containing, hypothalamic magnocellular neurons of the SON/PVN and in neurohypophysial nerve terminals of posterior pituitary gland; (2) agmatine may serve as a physiological neuromodulator by regulating the voltage-gated Ca(2+) channel and, as a result, the release of AVP from neurohypophysial nerve terminals.     

Optical imaging of intrinsic signals in somatosensory cortex

The experiments address the problem of bimanual coordination in a familiar task of everyday life. A goal-directed drawer-pulling task, with asymmetrical assignments among hands, was analyzed with the objective to detect discrete kinematic events ('anchors') that potentially could serve in proper goal synchronization. The left hand reached out for the drawer and opened it while the right hand performed a prehension movement to pick up a peg from the drawer. The task was smoothly performed, independently of vision. Typically, trajectories and velocity profiles of the leading pull-hand were more stereotypical than the more variable ones of the pick-hand. The pull-hand had a large velocity peak during reaching, followed by a small peak during pulling. Velocity profiles of the pick-hand were not bell-shaped and exhibited one or two broad waves, often with an irregular and probing evolution. Velocity profiles of both hands were aligned with the first or the second velocity peak of the leading pull-hand. In the majority of cases, temporal associations of events in the kinematics of the two limbs could thus be identified, which could serve to synchronize the hands at the goal. The nearly straight biphasic reach-and-pull trajectory of the leading hand contrasted with the more curved trajectory of the right pick-hand whereas, in the same unimanual action, the latter trajectories were quasi-rectilinear. Changing constraints (no vision, cutaneous anesthesia of pulling fingers) could change the coordination pattern. We argue that bimanual coordination relies on two interacting mechanisms: (1) feedforward control on the basis of sensorimotor memory; (2) temporal adjustments during the evolving bimanual synergy. Multiple strategies, imposed by the leading pull-hand, appeared to be responsible for feedback-induced corrections in the pick-hand and were found to contribute to the goal-invariance and to the principle of motor equivalence.