The role of objective cognitive dysfunction in subjective cognitive complaints after stroke.

BACKGROUND AND PURPOSE: Objective cognitive performance (OCP) is often impaired in patients post-stroke but the consequences of OCP for patient-reported subjective cognitive complaints (SCC) are poorly understood. We performed a detailed analysis on the association between post-stroke OCP and SCC. METHODS: Assessments of OCP and SCC were obtained in 208 patients 3 months after stroke. OCP was evaluated using conventional and ecologically valid neuropsychological tests. Levels of SCC were measured using the CheckList for Cognitive and Emotional (CLCE) consequences following stroke inventory. Multivariate hierarchical regression analyses were used to evaluate the association of OCP with CLCE scores adjusting for age, sex and intelligence quotient. Analyses were performed to examine the global extent of OCP dysfunction (based on the total number of impaired neuropsychological tests, i.e. objective cognitive impairment index) and for each OCP test separately using the raw neuropsychological (sub)test scores. RESULTS: The objective cognitive impairment index for global OCP was positively correlated with the CLCE score (Spearman's rho = 0.22, P = 0.003), which remained significant in multivariate adjusted models (ß = 0.25, P = 0.01). Results for the separate neuropsychological tests indicated that only one task (the ecologically valid Rivermead Behavioural Memory Test) was independently associated with the CLCE in multivariate adjusted models (ß = -0.34, P < 0.001). CONCLUSIONS: Objective neuropsychological test performance, as measured by the global dysfunction index or an ecologically valid memory task, was associated with SCC. These data suggest that cumulative deficits in multiple cognitive domains contribute to subjectively experienced poor cognitive abilities in daily life in patients post-stroke.

The Temporal Pattern of a Lesion Modulates the Functional Network Topology of Remote Brain Regions.

Focal brain lesions can alter the morphology and function of remote brain areas. When the damage is inflicted more slowly, the functional compensation by and structural reshaping of these areas seem to be more effective. It remains unclear, however, whether the momentum of lesion development also modulates the functional network topology of the remote brain areas. In this study, we compared resting-state functional connectivity data of patients with a slowly growing low-grade glioma (LGG) with that of patients with a faster-growing high-grade glioma (HGG). Using graph theory, we examined whether the tumour growth velocity modulated the functional network topology of remote areas, more specifically of the hemisphere contralateral to the lesion. We observed that the contralesional network topology characteristics differed between patient groups. Based only on the connectivity of the hemisphere contralateral to the lesion, patients could be classified in the correct tumour-grade group with 70% accuracy. Additionally, LGG patients showed smaller contralesional intramodular connectivity, smaller contralesional ratio between intra- and intermodular connectivity, and larger contralesional intermodular connectivity than HGG patients. These results suggest that, in the hemisphere contralateral to the lesion, there is a lower capacity for local, specialized information processing coupled to a higher capacity for distributed information processing in LGG patients. These results underline the utility of a network perspective in evaluating effects of focal brain injury.

Group and Individual Change in Cognitive Functioning in Patients With 1 to 10 Brain Metastases Following Gamma Knife Radiosurgery.

AIMS: Stereotactic radiosurgery is increasingly used to treat multiple (four or more) brain metastases. Preserving cognitive functions is a highly relevant treatment goal because cognitive deteriorations may negatively affect a patient's quality of life. The aim of this study was to assess cognitive change, at the group and individual level, in patients with 1 to 10 brain metastases up to 9 months after Gamma Knife radiosurgery (GKRS). MATERIALS AND METHODS: Ninety-two patients with 1 to 10 newly diagnosed brain metastases, expected survival >3 months and Karnofsky Performance Status (KPS) ≥70 and 104 non-cancer controls were included. A neuropsychological test battery was administered before GKRS (n = 92) and at 3 (n = 66), 6 (n = 52) and 9 (n = 41) months after GKRS. The course of test performances, while taking into account practice effects, was analysed using linear mixed models. Pre-GKRS predictors of cognitive trajectories were analysed. To determine proportions of individuals with cognitive changes, reliable change indices, with correction for practice effects, were calculated. RESULTS: At the group level, immediate memory, working memory and information processing speed significantly improved over 9 months after GKRS. There were no cognitive declines. Neither number nor volume of brain metastases influenced cognitive change over time. At the individual level, proportions of patients with stable, improved or declined performances were comparable with controls, except for information processing speed (more individuals with improvements in patients) and motor dexterity (more improvements and declines in patients). CONCLUSIONS: Cognitive functioning in patients with 1 to 10 brain metastases was preserved, or improved, up to 9 months after GKRS. Neither number nor volume of brain metastases influenced cognitive performance.

Volumes of brain structures in twins discordant for schizophrenia.

BACKGROUND: The study was designed to examine the relative contributions of genetic and nongenetic factors to structural brain abnormalities in schizophrenia and subjects at risk to develop the disorder. METHODS: The brains of 15 monozygotic and 14 same-sex dizygotic twins discordant for schizophrenia (patients) and 29 healthy twins pair-wise matched for zygosity, sex, age, and birth order were studied using high-resolution magnetic resonance imaging scans. RESULTS: Intracranial and whole-brain corrected frontal lobe volumes were smaller (4.6% and 2.7%, respectively) in discordant monozygotic twins as compared with healthy monozygotic twins. Irrespective of zygosity, discordant twins had smaller whole-brain (2%), parahippocampal (9%), and hippocampal (8%) volumes than healthy twins. Moreover, patients had smaller whole-brain volumes (2. 2%) than their nonschizophrenic cotwins, who in turn had smaller brains (1%) than healthy twins. Lateral and third-ventricle volumes were increased in discordant dizygotic twins as compared with healthy dizygotic twins (60.6% and 56.6%, respectively). Finally, within discordant twins, lateral ventricles were larger (14.4%) in patients than in their nonschizophrenic cotwins. CONCLUSIONS: Smaller intracranial volumes in the monozygotic patients and their cotwins suggest that increased genetic risk to develop schizophrenia is related to reduced brain growth early in life. The additional reduction in whole-brain volume found in the patients suggests that the manifestation of the disorder is related to (neurodegenerative) processes that are most likely nongenetic in origin.

Cognitive status and quality of life in patients with suspected versus proven low-grade gliomas.

BACKGROUND: The preferred management of patients with suspected low-grade gliomas (S-LGG) remains controversial. The benefits of resection or radiotherapy early in the course of the disease have not been proven in terms of survival. Little is known about the effects of early therapy on quality of life (QOL) and cognitive status. The authors compared functional status, QOL, and cognitive status of patients suspected of having a LGG, in whom treatment was deferred, and patients with proven LGG (P-LGG), who underwent early surgery. METHODS: The authors recruited 24 patients suspected of having an LGG. These patients were matched with 24 patients with a histologically proven LGG and healthy control subjects for educational level, handedness, age, and gender. The two patient groups were also matched for tumor laterality, use of anticonvulsants, and interval between diagnosis and testing. Functional status was determined in both patient groups. QOL and cognitive status were compared between the three groups. RESULTS: Matching criteria and functional status did not differ significantly between groups. Both patient groups scored worse on QOL scales than healthy control subjects. Unoperated patients with S-LGG scored better on most items than patients with P-LGG. Cognitive status was worse in both groups than in healthy control subjects, but, again, patients with S-LGG performed better than patients with P-LGG. CONCLUSION: These data suggest that a wait-and-see policy in patients with S-LGG has no negative effect on cognitive performance and QOL.

Does the Schizotypal Personality Questionnaire reflect the biological-genetic vulnerability to schizophrenia?

We investigated whether the Schizotypal Personality Questionnaire (SPQ) [Schizophr. Bull. 17 (1991) 555.] could be an indicator of the biological-genetic vulnerability to schizophrenia. We hypothesized that the mean scores on three dimensions of the SPQ of different groups of relatives of patients with schizophrenia would parallel their risk for developing schizophrenia. The SPQ was administered to 51 first-episode schizophrenia patients, 63 parents of schizophrenia patients, 42 siblings of schizophrenia patients and 12 children of schizophrenia patients. Patients differed from the relatives on all three dimensions. Siblings and children scored significantly higher than parents on Positive Schizotypy, and the insignificant difference between the siblings and children was in the expected direction. The results could not be explained by the differences in age, sex, IQ or substance abuse. No differences were found for Disorganization Schizotypy between the relatives. Children scored higher than parents on Negative Schizotypy. The current study offers support to the hypothesis that the positive dimension of SPQ reflects the genetic vulnerability to schizophrenia.

Differentiating between low and high susceptibility to schizophrenia in twins: the significance of dermatoglyphic indices in relation to other determinants of brain development.

Both the skin and the brain develop from the same ectoderm and it is thought, therefore, that dermatoglyphics are informative for early disturbances in brain development in schizophrenia. This study was aimed at investigating the differences in both digital and palmar dermatoglyphic indices between twins discordant for schizophrenia and control twins. Furthermore, the significance of dermatoglyphic indices in relation to other determinants of brain development with regard to the susceptibility to schizophrenia was investigated. Data on dermatoglyphic indices of the hand and the palm were obtained from 21 same-sex discordant and 37 same-sex control twins. For 19 discordant and 25 control twins, there was also data available on brain volumes. Non-genetic intra-uterine circumstances early in pregnancy (10-13 weeks of gestation) are associated with a susceptibility to schizophrenia, since both the twins with schizophrenia and the unaffected co-twins showed more fluctuating asymmetry of the finger ridges (P<0.01), and marginally higher absolute finger ridge counts (P=0.06) than control twin pairs. Fluctuating asymmetry of the finger ridges was as important as whole brain and left hippocampal volumes in differentiating twins with a high susceptibility to schizophrenia from those with a low susceptibility.

Activation of striate cortex in the absence of visual stimulation: an fMRI study of synesthesia.

It has been suggested that internally generated visual perception involves the primary visual cortex V1. To test this hypothesis, a functional MRI study was conducted with a female subject with orthographic color-word synesthesia. This subject was selected as she reported clear involuntary visualization of auditorily presented verbal material. Hearing a word resulted in seeing the word in a particular color. fMRI scans were acquired while the subject performed two verbal tasks (passive listening to words and verbal fluency). Significant activity was detected in primary visual cortex, in the absence of external visual stimulation. This finding provides evidence for a role of modulatory feedback connections between associative and primary visual areas in visual experience without direct visual stimulation.

Why don't neurosurgery patients return for neuropsychological follow-up? Predictors for voluntary appointment keeping and reasons for cancellation.

Neuropsychological follow-up appointments are important for patients who have had intracranial surgery because cognitive deficits are common in this population and prognosis is not always optimistic. Unfortunately some patients cancel or do not show up. The current study attempted to identify predictors of non-attendance in this population. A total of 428 patients recruited over 2 years with a scheduled neuropsychological follow-up appointment after intracranial surgery in the St. Elisabeth Hospital, Tilburg, The Netherlands were included. Demographic, clinical, and other miscellaneous variables were extracted from medical records. Of this total population, 42% were non-attenders. The predictors of non-attendance were as follows: patients who had subdural hematomas and/or malignant tumors (compared to those who had other diagnoses prior to intracranial surgery); those who had been transferred to another hospital (compared to those sent home); those who had been referred for further medical treatment before the appointment; a shorter time interval between discharge and follow-up appointment; and finally, if the patient's home was further away from the hospital. Patients who undergo intracranial surgery are a very heterogeneous group with different needs. Neuropsychological follow-up after surgery may be important for some patients (the better-functioning and/or those with cognitive complaints) but perhaps not for others (those with more severe prognoses and/or no complaints). We provide suggestions which should increase attendance in those who could benefit from follow-up neuropsychological assessment.

Effects on cognitive functioning after olanzapine-ziprasidone crossover in recent-onset schizophrenia.

INTRODUCTION: To enhance functional outcome in schizophrenia improvement of cognitive symptoms is crucial. EXPERIMENTAL PROCEDURES: Using a comprehensive test battery, this follow-up examines cognitive effects in patients with recent-onset schizophrenia after a change of medication following insufficient clinical response and intolerance. RESULTS: After eight weeks cognitive outcomes had not improved in the patients having switched from olanzapine to ziprasidone (n=11; mean dose 136 mg) nor in those having switched from ziprasidone to olanzapine (n=10; mean 16 mg), while the symptoms of patients maintaining olanzapine (n=18; mean 10.9 mg) or ziprasidone (n=18; mean 88.9 mg) treatment had not improved further. DISCUSSION: The findings suggest that also in early-stage schizophrenia the antipsychotics tested affect cognitive symptoms similarly.