Robert Vandorpe

The Consortium to Investigate Vascular Impairment of Cognition: methods and first findings.

BACKGROUND The Consortium to Investigate Vascular Impairment of Cognition (CIVIC) is a Canadian, multi-centre, clinic-based prospective cohort study of patients with Vascular Cognitive Impairment (VCI). We report its organization and the impact of diagnostic criteria on the study of VCI. METHODS Nine memory disability clinics enrolled patients and recorded their usual investigations and care. A case report form included all vascular dementia (VaD) individual criteria for each of four sets (National Institute of Neurological Disorders and Stroke (NINDS-AIREN), Alzheimers Disease Diagnostic Treatment Centers (ADDTC), the ICD-10 Classification of Mental and Behavioural Disorders (ICD-10), and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV)) of consensus-based diagnostic criteria and for the Hachinski Ischemia Score (HIS). Investigators, having completed the case report form, were asked to make a clinical judgement about the cognitive diagnosis based on the best available information, including neuroimaging. RESULTS Of 1,347 patients (mean age 72 years; 56% women), 846 (63%) were diagnosed with dementia and 324 (24%) were diagnosed with VCI. The proportion of patients diagnosed with VaD by the diagnostic criteria was: 23.9% (n = 322) by DSM-IV, 10.2% (n = 137) by HIS, 4.3% (n = 58) by ICD-10, 3.8% (n = 51) by ADTCC, and 3.6% (n = 48) by NINDS-AIREN. Judged against a clinical diagnosis of VaD, the sensitivity/specificity of each was: DSM-IV (0.77/0.80); HIS (0.41/0.92); ICD-10 (0.29/0.98); ADTCC (0.24/0.98); NINDS-AIREN (0.42/0.995). Compared with a clinical diagnosis of VCI, sensitivities were lower for the diagnostic criteria, reflecting the exclusion of patients who did not have dementia. CONCLUSIONS Consensus-based criteria for VaD omit patients who do not meet dementia criteria that are modeled on Alzheimers disease. Even for patients who do, the proportion identified with VaD varies widely. Criteria based on empirical analyses need to be developed and validated.

Gradients of detection in neglect: comparison of peripersonal and extrapersonal space☆

Previous studies of target-cancellation performance in visuospatial neglect patients have reported lateral (left-right) and radial (near-far) gradients of attentional ability. The purpose of the present study was to replicate the reported attentional gradients in peripersonal space (within arms reach) and to examine whether lateral gradients of detection also appear in extrapersonal space (beyond arms reach), using equivalent tasks with no manual requirement. The relationship between radial gradients in peripersonal space and neglect severity (degree of lateral gradient) in extrapersonal space was also of interest. Right-hemisphere stroke subjects, with and without neglect, and healthy control subjects named visual targets on scanning sheets placed in peripersonal and extrapersonal space. The neglect group showed lateral gradients of increasing target detection from left to right in both peripersonal and extrapersonal space, which were not evident in the performance of either of the control groups. Double dissociations of neglect severity in peripersonal and extrapersonal space were also found in analyses of individual performance. Lesion analyses showed that peripersonal neglect was related to dorsal stream damage and extrapersonal neglect was related to ventral stream damage. Group analyses showed no significant radial gradients in peripersonal space in the three groups. In addition, while analyses of some individuals found significant near-far and far-near radial gradients, there was no correlation between radial gradients in peripersonal space and neglect severity in extrapersonal space. These results are discussed in terms of theorised hemispheric mechanisms of spatial attention and the relationship of neglect in the two co-ordinate spaces to the extent and location of damaged neurons in the right hemisphere.

Reduced anterior internal capsule and thalamic volumes in first-episode psychosis.

BACKGROUND The thalamus is the gateway for sensory and motor information en route to the cortex. Information is processed via thalamocortical and corticothalamic pathways coursing through the internal capsules. In this study, we investigated the relationship between the anterior limb of the internal capsule, posterior limb of the internal capsule, and thalamus in first-episode psychosis (FEP). METHODS Twenty-nine FEP subjects (26 DSM-IV schizophrenia, 2 schizoaffective disorder, 1 psychosis not otherwise specified) and 22 healthy volunteers participated in this study. Anterior limb of the internal capsule (AIC), posterior limb of the internal capsule (PIC), and the thalamus volumes were manually determined from MRI scans. RESULTS FEP subjects had reduced AIC volumes (F(1,45)=6.18, p=0.017) and thalamic volumes (F(1,45)=8.00, p=0.007) compared to healthy volunteers. PIC volumes did not differ. Significant correlations between AIC volumes and thalamic volumes were observed in subjects with FEP, but not in healthy volunteers. Negative relationships between thalamic volumes and symptom severity were also observed. CONCLUSIONS The AIC and thalamic volumes were reduced in subjects with FEP compared to healthy volunteers. Abnormalities in thalamocortical and orticothalamic pathways may contribute to functional disruption of neural circuits in psychosis.

Clinical and radiographic subtypes of vascular cognitive impairment in a clinic-based cohort study

BACKGROUND AND PURPOSE There is a need for empirical studies to define criteria for vascular cognitive impairment (VCI) subtypes. In this paper, we report the predictive validity of a subtype classification scheme based on clinical and radiographic features. METHODS Nine Canadian memory clinics participated in the Consortium to Investigate Vascular Impairment of Cognition. This cohort consisted of 1347 patients, of whom 324 had VCI, and was followed for up to 30 months. RESULTS Clinical and neuroimaging features defined three subtypes: vascular cognitive impairment, no dementia, (n=97), vascular dementia (n=101) and mixed neurodegenerative/vascular dementia (n=126). Any ischemic lesion on neuroimaging increased the odds (odds ratio=9.31; 95% confidence interval 6.46, 13.39) of a VCI diagnosis. No VCI subtype, however, was associated with a specific neuroimaging abnormality. Compared to those with no cognitive impairment, patients with each VCI subtype had higher rates of death and institutionalization (hazard ratio for combined adverse events=6.08, p<0.001). CONCLUSIONS Both clinical features and radiographic features help establish a diagnosis of VCI. The outcomes of VCI subtypes, however, are more strongly associated with clinical features than with radiographic ones.

A longitudinal study on the effects of typical versus atypical antipsychotic drugs on hippocampal volume in schizophrenia

BACKGROUND Previous studies have reported that hippocampal volumes correlate with symptom severity in schizophrenia. This longitudinal study measured changes in symptoms and hippocampal volume in patients switched from typical antipsychotics to olanzapine. METHODS MRI scans were acquired from patients with chronic schizophrenia (n=10) and healthy volunteers (n=20). At baseline, patients were treated with typical antipsychotics for at least one year, then switched to olanzapine, and rescanned approximately one year later. RESULTS Olanzapine treatment resulted in no significant change in right or left hippocampal volume. Individual changes in right hippocampal volume correlated significantly with changes in symptoms. CONCLUSIONS Hippocampal volume change may serve as a marker of symptom change in patients on olanzapine.

Neuroanatomy of coprolalia in Tourette syndrome using functional magnetic resonance imaging

OBJECTIVE To determine the neural substrates of phonic tics in Tourette syndrome (TS) using functional magnetic resonance imaging (fMRI) and compare with a proposed tic-generating network (TGN). PATIENTS One with TS and one normal control. METHODS fMRI scans were obtained on the TS patient during which numerous unsuppressed phonic tics occurred and, along with the scanner noise, were recorded on audiotape. The control underwent the same functional MRI sequence but mimicked the tics within predetermined, on-off time blocks. Fuzzy clustering (FC) methods were used to generate the activation maps. RESULTS The TS patient and control showed fMRI activation in the left middle frontal gyrus and right precentral gyrus. The TS patient also had activity in the caudate nucleus, cingulate gyrus, cuneus, left angular gyrus, left inferior parietal gyrus, and occipital gyri. CONCLUSIONS fMRI, using an FC analysis, is a viable technique for studying TS patients with phonic tics. These results give further support to the hypothesis of a tic-generating circuit model. Further studies are required to confirm our data.

CT perfusion for confirmation of brain death.

SUMMARY: For pronouncing brain death, unlike CTP, the 2-phase CTA gives no functional information and is limited by inadvertent delay of the second acquisition, which may give false-negative results. The purpose of our study was to compare CTP and CTA derived from the CTP data with the Dupas and Frampas criteria for confirmation of brain death. A retrospective review of CTP in 11 consecutive patients for confirmation of brain death showed a sensitivity of 72.7% for 7- and 4-point scores, 81.8% for opacification of the ICV, and 100% for CTP scores in the brain stem. CTA obtained from the CTP data showed similar sensitivity in the diagnosis of brain death. This protocol also reduces the iodinated contrast dose and is less operator-dependent. The addition of the functional tools of CTP increased the sensitivity of CTA in the confirmation of brain death.

SILK flow diverter for treatment of intracranial aneurysms: initial experience and cost analysis

Background The flow diverting stent is a new and expansive tool in the endovascular therapy of complex intracranial aneurysms. We present our experience using SILK flow diverter (SFD) in patients with complex intracranial aneurysms, and a cost analysis. Methods Between September 2010 and May 2012, 19 consecutive patients with 29 complex intracranial aneurysms were treated with SFD without the adjunctive use of coils. We retrospectively evaluated the technical aspects, thromboembolic events, adjunctive therapies, and short term results in patients with complex intracranial aneurysms treated with SFD. A cost analysis of patients who were treated with SFD was performed and compared with similar sized aneurysms coiled with stent assisted coiling. Results The primary technical success rate was 100%. An adjunctive device was required in two of our patients. The technique related complication rate and the 30 day mortality and morbidity rates were 5% (1/20) and 10% (2/20), respectively. We had a total of 263 patient months of clinical and 166 patient months of imaging follow-up. Follow-up imaging revealed two asymptomatic occlusions of the parent artery. Complete occlusion of the aneurysm with fully patent parent artery was observed in 59% of patients where follow-up images were available. The cost analysis showed that the mean cost of treatment with SFD was significantly cheaper compared with the presumed cost of stent assisted coiling (p<0.001). Conclusions The SFD provides a very feasible, efficient, relatively safe, and cost effective method to treat complex intracranial aneurysms without the use of adjunct coiling.

Evaluation of Common Structural Brain Changes in Aging and Alzheimer Disease with the Use of an MRI-Based Brain Atrophy and Lesion Index: A Comparison Between T1WI and T2WI at 1.5T and 3T

This study assesses the usefulness of a set of established structural findings in Alzheimer disease with various MRI sequences at 2 different field strengths in 127 subjects. Scores of atrophy and lesion burden were reliable across sequences and unit strength and were lowest in individuals with cognitive impairment, higher in those with Alzheimer disease, and also correlated with age, cognitive performance, and amyloid-β test. Although the results were slightly better at 3T, the authors concluded that even at 1.5T scores were reliable. BACKGROUND AND PURPOSE: The Brain Atrophy and Lesion Index combines several common, aging-related structural brain changes and has been validated for high-field MR imaging. In this study, we evaluated measurement properties of the Brain Atrophy and Lesion Index by use of T1WI and T2WI at 1.5T and 3T MR imaging to comprehensively assess the usefulness of the lower field-strength testing. MATERIALS AND METHODS: Data were obtained from the Alzheimers Disease Neuroimaging Initiative. Images of subjects (n = 127) who had T1WI and T2WI at both 3T and 1.5T on the same day were evaluated, applying the Brain Atrophy and Lesion Index rating. Criterion and construct validity and interrater agreement were tested for each field strength and image type. RESULTS: Regarding reliability, the intraclass correlation coefficients for the Brain Atrophy and Lesion Index score were consistently high (>0.81) across image type and field strength. Regarding construct validity, the Brain Atrophy and Lesion Index score differed among diagnostic groups, being lowest in people without cognitive impairment and highest in those with Alzheimer disease (F > 5.14; P < .007). Brain Atrophy and Lesion Index scores correlated with age (r > 0.37, P < .001) and cognitive performance (r > 0.38, P < .001) and were associated with positive amyloid-β test (F > 3.96, P < .050). The T1WI and T2WI Brain Atrophy and Lesion Index scores were correlated (r > 0.93, P < .001), with the T2WI scores slightly greater than the T1WI scores (F > 4.25, P < .041). Regarding criterion validation of the 1.5T images, the 1.5T scores were highly correlated with the 3T Brain Atrophy and Lesion Index scores (r > 0.93, P < .001). CONCLUSIONS: The higher field and T2WI more sensitively detect subtle changes in the deep white matter and perivascular spaces in particular. Even so, 1.5T Brain Atrophy and Lesion Index scores are similar to those obtained by use of 3T images. The Brain Atrophy and Lesion Index may have use in quantifying the impact of dementia on brain structures.

Anterior internal capsule volumes increase in patients with schizophrenia switched from typical antipsychotics to olanzapine

Abnormalities in connectivity are thought to contribute to the symptoms of schizophrenia. Accumulating evidence suggests that antipsychotic medication affects both subcortical and cortical grey and white matter volumes. The goal of this study was to investigate the effects of antipsychotic medication on two white matter tracts: a subcortical-cortical tract, the anterior and posterior limbs of the internal capsule; and a cortical-cortical tract, the corpus callosum. Magnetic resonance imaging was conducted on 10 chronic schizophrenia patients treated with typical antipsychotics and 20 healthy controls at baseline. Patients were switched to olanzapine and both groups were rescanned after 1 year. At baseline, the volume of the anterior limb of the internal capsule was 24% smaller in typical-treated patients than controls (p = 0.009). Patients treated with greater amounts of chlorpromazine-equivalent daily dosage had smaller anterior internal capsule volumes at baseline (r = −0.65, p = 0.04). At follow-up, after being switched to olanzapine, there were no significant differences between patients and controls. Patients with schizophrenia had a significant 25% increase in anterior internal capsule volume from baseline to follow-up compared with controls (p = 0.04). These effects were most prominent in the anterior limb of the internal capsule, which consists of fronto-thalamic pathways, and were not statistically significant in the posterior limb of the internal capsule or corpus callosum. Olanzapine may be effective in normalizing fronto-thalamic structural connectivity in schizophrenia.