Ron Hijman

Subclinical dopaminergic dysfunction in asymptomatic Parkinson's disease patients' relatives with a decreased sense of smell

By the time a clinical diagnosis of Parkinsons disease (PD) is made, a significant loss of dopaminergic neurons has already occurred. Identifying patients in the period between the presumed onset of dopaminergic cell loss and the appearance of clinical parkinsonism may be of major importance in the development of effective neuroprotective treatment strategies. In an effort to develop a feasible strategy to detect preclinical PD, a combination of olfactory processing tasks, including odor detection, odor identification, and odor discrimination was used to select groups of hyposmic and normosmic individuals from a total of 250 relatives (parents, siblings, or children) of subjects with PD. Single photon emission computed tomography (SPECT) with [123I]β‐CIT as a dopamine transporter ligand was used to assess nigrostriatal dopaminergic function in 25 hyposmic and 23 normosmic relatives of PD patients. An abnormal reduction in striatal dopamine transporter binding was found in 4 out of 25 hyposmic relatives of PD patients, 2 of whom subsequently developed clinical parkinsonism, and in none of the 23 normosmic relatives. These observations demonstrate that subclinical reductions in dopamine transporter binding can be detected in asymptomatic relatives of sporadic PD patients by means of [123I]β‐CIT and SPECT. The results further indicate that olfactory deficits may precede clinical motor signs in PD.

Volumetric analysis of frontal lobe regions in schizophrenia : relation to cognitive function and symptomatology

BACKGROUND The purpose of this study was to examine the structure of dorsolateral, medial, and orbital regions of the frontal lobe in schizophrenia, and to determine whether their volumetric measurements were related to cognitive function and symptomatology. METHODS High resolution magnetic resonance imaging scans of the brains of 14 schizophrenic patients and 14 closely matched healthy controls were acquired. Volumes of gray and white matter of the left and right dorsolateral, medial, and orbital prefrontal brain regions were measured. Tests of verbal and visual memory and executive functions were used to assess cognitive function. The SANS and SAPS were used to obtain symptom ratings in patients. RESULTS Data of 13 schizophrenic patients were analyzed. Patients showed a general, though not significant, decrease in volumes of frontal regions as compared to controls. In patients, but not in controls, smaller left and right prefrontal gray matter volumes were significantly correlated with impaired performance on immediate recall in verbal and visual memory and semantic fluency. Furthermore, in patients, smaller total orbitofrontal gray matter volume was significantly correlated with more severe negative symptomatology (rs = -.76, p = .006). CONCLUSIONS These findings suggest that in schizophrenia, deficits in verbal and visual memory and semantic fluency and negative symptoms may be related to (subtle) abnormalities in frontal lobe structure.

The five-factor model of the Positive and Negative Syndrome Scale I: confirmatory factor analysis fails to confirm 25 published five-factor solutions

OBJECTIVE The aim of this study was to test the goodness-of-fit of all previously published five-factor models of the Positive and Negative Syndrome Scale (PANSS). METHODS We used confirmatory factor analysis (CFA) with a large data set (N = 5769). RESULTS The different subsamples were tested for heterogeneity and were found to be homogeneous. This indicates that despite variability in age, sex, duration of illness, admission status, etc., in the different subsamples, the structure of symptoms is the same for all patients with schizophrenia. Although previous research has shown that a five-factor model fits the data better than models with three or four factors, no satisfactory fit for any of the 25 published five-factor models was found with CFA. CONCLUSIONS Variability in age, sex, admission status and duration of illness has no substantial effect on the structure of symptoms in schizophrenia. The lack of fit can be caused by ill-defined items that aim to measure several properties in a single rating. Another explanation is that well-defined symptoms can have two or more causes. Then a double or triple loading item should not be discarded, but included because the complexity of symptoms in schizophrenia is represented by these multiple loadings. Such a complex model not only needs confirmation by CFA, but also has to be proven stable. A 10-fold cross-validation is suggested to develop a complex and stable model.

Cognitive basis of hallucinations in schizophrenia: role of top-down information processing

Hallucinations in schizophrenia have been regarded to result from the erroneous attribution of internally generated information to an external source. Distortions in mental imagery may underlie such confusions. We investigated performance of 77 subjects on multiple behavioral measures of auditory and visual mental imagery and perception, and a measure of reality monitoring. Comparisons were made between performance of schizophrenia patients with (N=22) and without (N=35) hallucinations and matched normal comparison subjects (N=20), after controlling for attentional factors. No differences emerged on any of the mental imagery measures, nor on reality monitoring accuracy. This suggests that there is no stable disposition towards abnormal mental imagery associated with hallucinations. However, for patients with active hallucinations (N=12), hallucination severity correlated positively with a measure of imagery-perception interaction in the auditory modality, r=0.70, p=0.01. Although preliminary, this finding is consistent with recent theoretical proposals in which hallucinations have been suggested to result from an increased influence of top-down sensory expectations on conscious perception.

Subjective ordering, short-term memory, and the frontal lobes.

Four tasks relying on short-term retention, i.e. digit span, missing scan, randomization span, and pointing span were presented to patients with frontal-lobe lesions and normal controls. Digit span was considered a measure of passive short-term memory, the other three tasks additionally reflect comparing processes, and two of these, the randomization and pointing spans, also measure active ordering by the subject. The results confirmed Petrides and Milners (Neuropsychologia 20, 249-262, 1982) hypothesis that frontal-lobe patients are typically deficient in subject-ordered tasks. It is also suggested that they are deficient in a spontaneous generation, rather than comparison component of subjective ordering.

The incidence of cognitive decline after (not) undergoing coronary artery bypass grafting: the impact of a controlled definition

Background:  After coronary artery bypass grafting (CABG), 20–30% of patients are reported to suffer from cognitive decline. Studies reporting these high incidences, however, have not included an appropriate control group.

Effect of a single dose of des-glycinamide-[Arg8]vasopressin or oxytocin on cognitive processes in young healthy subjects

A single dose of des-glycinamide-[Arg8]vasopressin (DGAVP, 2 mg intranasal) or oxytocin (OXT, 20 IU intranasal) was given to female and male volunteers, respectively, in a placebo-controlled double-blind trial. Memory, vigilance, attention, and mood were tested starting 10 minutes after treatment. The DGAVP dose improved delayed recognition of abstract words when measured 1 week after treatment and reduced the intercept of a memory comparison task (Sternberg paradigm). A trend was present for DGAVP and OXT to affect learning, i.e., storage processes of verbal memory in an opposite way; DGAVP improved, while OXT attenuated initial storage and the rate of storage. No treatment effects on visual memory and vigilance were found. Of the mood measures, vigor was reduced immediately after treatment with OXT.

Association between early and three month cognitive outcome after off-pump and on-pump coronary bypass surgery

Objective: To describe the association between cognitive outcome in the first postoperative week and that at three months after both off-pump and on-pump coronary bypass surgery, and to make a direct comparison of early cognitive outcome after off-pump versus on-pump surgery. Design: Randomised trial with an additional prediction study within the two randomised groups. Setting: Three centres for heart surgery in the Netherlands. Patients: 281 patients, mean age 61 years. Interventions: Participants were randomly assigned to off-pump or on-pump coronary bypass surgery. Main outcome measures: Cognitive outcome, assessed by psychologists who administered neuropsychological tests one day before and four days and three months after surgery. A logistic regression model was used to study the predictive association between early cognitive outcome, together with eight clinical variables, and cognitive outcome after three months. Results: Cognitive outcome in the first week after surgery was determined for 219 patients and was a predictor of cognitive decline after three months. This association was stronger in on-pump patients (odds ratio (OR) 5.24, p < 0.01) than in off-pump patients (OR 1.80, p  =  0.23). Early decline was present in 54 patients (49%) after off-pump surgery and 61 patients (57%) after on-pump surgery (OR 0.73, p  =  0.25). Conclusions: In patients undergoing first time coronary bypass surgery, early cognitive decline predicts cognitive outcome after three months. Early cognitive decline is not significantly influenced by the use of cardiopulmonary bypass.

Perception, mental imagery and reality discrimination in hallucinating and non-hallucinating schizophrenic patients.

OBJECTIVES In this study the hypothesis was tested that hallucinations result from confusing external and internal stimulus sources, i.e., perception and imagery, respectively. DESIGN AND METHODS Thirteen hallucinating and 19 non-hallucinating schizophrenic patients, as well as 14 control participants performed multiple tests of perception, vividness of mental imagery and the ability to discriminate between them (reality discrimination). These functions were tested in both the auditory and the visual modalities. RESULTS There were no group differences on perceptual acuity. The results on one imagery task indicated that for the hallucinating patients, the relative, but not the absolute, level of vividness of mental images might be higher in the auditory modality, which was the modality in which 12 of the patients also experienced hallucinations, than in the visual modality. Finally, there was a positive relationship between severity of (auditory) hallucinations and reality discrimination problems. CONCLUSIONS Hallucinations may result from increased vividness of mental imagery, and their severity increases with larger impairments in reality discrimination. It is recommended that research into, and cognitive behavioural therapy for, hallucinations should also focus on their sensory qualities.

Neuropsychological performance is related to current social and occupational functioning in veterans with posttraumatic stress disorder.

Background: Several studies have reported deficits in both immediate and delayed recall of verbal memory in patients with posttraumatic stress disorder (PTSD). However, most of these studies had several methodological disadvantages. None of these studies assessed parameters related to social or occupational functioning. Methods: Fifty Dutch veterans of UN peacekeeping missions (25 with PTSD and 25 without PTSD) were assessed with a comprehensive neuropsychological test battery consisting of four subtests of the Wechsler Adult Intelligence Scale‐III, California Verbal‐Learning Test, and the Rey Auditory Verbal‐Learning Test. Veterans with PTSD were free of medication and substance abuse. Results: Veterans with PTSD had similar total intelligence quotient scores compared to controls, but displayed deficits of figural and logical memory. Veterans with PTSD also performed significantly lower on measures of learning and immediate and delayed verbal memory. Memory performance accurately predicted current social and occupational functioning. Conclusions: Deficits of memory performance were displayed in a sample of medication‐ and substance abuse‐free veterans with PTSD. Deficits in memory performance were not related to intelligence quotient, length of trauma exposure, or time since trauma exposure. This study showed that cognitive performance accurately predicted current social and occupational functioning in veterans with PTSD. Depression and Anxiety, 2009.