Search PubMed⌕ Search

Biomedical subjects

P Scheltens

Publications and source records attributed to P Scheltens.

At least 55 records · Page 3Linked to original sources
PubMed2003

Visual rating of age-related white matter changes on magnetic resonance imaging: scale comparison, interrater agreement, and correlations with quantitative measurements.

BACKGROUND AND PURPOSE: To provide further insight into the MRI assessment of age-related white matter changes (ARWMCs) with visual rating scales, 3 raters with different levels of experience tested the interrater agreement and comparability of 3 widely used rating scales in a cross-sectional and follow-up setting. Furthermore, the correlation between visual ratings and quantitative volumetric measurement was assessed. METHODS: Three raters from different sites using 3 established rating scales (Manolio, Fazekas and Schmidt, Scheltens) evaluated 74 baseline and follow-up scans from 5 European centers. One investigator also rated baseline scans in a set of 255 participants of the Austrian Stroke Prevention Study (ASPS) and measured the volume of ARWMCs. RESULTS: The interrater agreement for the baseline investigation was fair to good for all scales (kappa values, 0.59 to 0.78). On the follow-up scans, all 3 raters depicted significant ARWMC progression; however, the direct interrater agreement for this task was poor (kappa, 0.19 to 0.39). Comparison of the interrater reliability between the 3 scales revealed a statistical significant difference between the scale of Manolio and that of Fazekas and Schmidt for the baseline investigation (z value, -2.9676; P=0.003), demonstrating better interrater agreement for the Fazekas and Schmidt scale. The rating results obtained with all 3 scales were highly correlated with each other (Spearman rank correlation, 0.712 to 0.806; P< or =0.01), and there was significant agreement between all 3 visual rating scales and the quantitative volumetric measurement of ARWMC (Kendall W, 0.37, 0.48, and 0.57; P<0.001). CONCLUSIONS: Our data demonstrate that the 3 rating scales studied reflect the actual volume of ARWMCs well. The 2 scales that provide more detailed information on ARWMCs seemed preferential compared with the 1 that yields more global information. The visual assessment of ARWMC progression remains problematic and may require modifications or extensions of existing rating scales.

Adult↗
PubMed2002

Radiotherapy-induced cerebral abnormalities in patients with low-grade glioma.

Abnormalities on CT or MRI and neuropsychological performance in patients with low-grade glioma, with (n = 23) or without (n = 16) prior cerebral radiotherapy, were evaluated. Cerebral atrophy was observed in 14 of 23 patients (61%) treated with prior radiotherapy, and in 1 of 16 patients (6%) without prior radiotherapy. White matter abnormalities were observed in six patients, all of whom were treated with prior radiotherapy. These radiologic cerebral abnormalities correlated with cognitive performance.

Adult↗
PubMed2002

A new rapid landmark-based regional MRI segmentation method of the brain.

BACKGROUND: Neurodegenerative and cerebrovascular diseases show a distinct distribution of regional atrophy and subcortical lesions. OBJECTIVE: To develop an easily applicable landmark-based method for segmentation of the brain into the four cerebral lobes from MRI images. METHOD: The segmentation method relies on a combination of anatomical landmarks and geometrical definitions. It is applied on the surface reconstruction of the MRI volume. The internal borders between the lobes are defined on the axial slices of the brain. The reliability of this method was determined from MRI scans of 10 subjects. To illustrate the use of the method, it was applied to MRI scans of an independent group of 10 healthy elderly subjects and 10 patients with vascular dementia to determine the regional distribution of white matter hyperintensities (WMH). RESULTS: The intra-rater relative error (and intra-class correlation coefficient) of the lobe segmentation ranged from 1.6% to 6.9% (from 0.91 to 0.99). The inter-rater relative error (and intra-class correlation coefficient) ranged from 1.4% to 5.2% (from 0.96 to 0.99). Density of WMH was significantly higher in all four lobes in VD patients compared to controls (p<0.05). Within each group, WMH density was significantly higher in frontal and parietal than in temporal and occipital lobes (p<0.05). CONCLUSION: This landmark based method can accommodate age and disease-related changes in brain morphology. It may be particularly useful for the study of neurodegenerative and cerebrovascular disease and for the validation of template-based automated techniques.

Aged↗
PubMed2002

Alzheimer's disease is not associated with altered concentrations of the nitric oxide synthase inhibitor asymmetric dimethylarginine in cerebrospinal fluid.

Nitric oxide (NO) may play a role in the pathophysiology of Alzheimer's disease (AD). Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, is involved in regulation of NO production. Recently it has been reported that dimethylarginine dimethylaminohydrolase, an enzyme that hydrolyses ADMA into citrulline and dimethylamine, is specifically elevated in neurons displaying cytoskeletal abnormalities and oxidative stress in AD. We hypothesized that this could lead to altered CSF concentrations of ADMA in AD. Measurement of ADMA and dimethylamine in CSF revealed no significant differences between AD patients (n = 20) and age-matched control subjects (n = 20). Our results suggest that in early stages of AD overall regulation of NO production by ADMA is not aberrant.

Aged↗
PubMed2002

Medial temporal lobe atrophy predicts Alzheimer's disease in patients with minor cognitive impairment.

OBJECTIVES: To investigate whether medial temporal lobe atrophy predicted outcome in patients with minor cognitive impairment and whether assessment of the medial temporal lobe could increase the predictive accuracy of age and delayed recall for outcome. Quantitative and qualitative methods of assessing the medial temporal lobe were also compared. METHODS: Patients with minor cognitive impairment older than 50 years (n=31) were selected from a memory clinic and were followed up for on average 1.9 years. The medial temporal lobe was assessed in three different ways: volumetry of the hippocampus, volumetry of the parahippocampal gyrus, and qualitative rating of medial temporal lobe atrophy (MTA). Outcome measures were Alzheimer type dementia or cognitive decline at follow up. Delayed recall was tested with a verbal learning test. RESULTS: Ten patients had experienced cognitive decline at follow up, of whom seven had probable Alzheimer type dementia. All medial temporal lobe measurements were associated with cognitive decline at follow up (p trend analysis between 0.001 (hippocampus) and 0.05 (parahippocampal gyrus)). Only the hippocampal volume and MTA score were associated with Alzheimer type dementia at follow up (p trend analysis respectively 0.003 and 0.01). All medial temporal lobe measurements increased the predictive accuracy of age and the delayed recall score for cognitive decline (p increase in predictive accuracy varied between <0.001 (hippocampus) and 0.02 (parahippocampal gyrus and MTA score)) and the hippocampal volume and the MTA score increased the predictive accuracy of age and the delayed recall score for Alzheimer type dementia (p= 0.02). CONCLUSIONS: The ability to detect patients at high risk for Alzheimer type dementia among those with minor cognitive impairment increases when data on age and memory function are combined with measures of medial temporal lobe atrophy. Volumetry of the hippocampus is preferred, but qualitative rating of medial temporal lobe atrophy is a good alternative.

Aged↗
PubMed2002

Alterations in brain activation during cholinergic enhancement with rivastigmine in Alzheimer's disease.

BACKGROUND: Rivastigmine enhances cholinergic activity and has been shown in clinical trials to decrease the rate of deterioration in Alzheimer's disease. It remains unclear where in the brain it exerts its effect. Functional magnetic resonance imaging (fMRI) can be used to measure changes in brain function and relate these to cognition. OBJECTIVES: To use fMRI to study brain activation with rivastigmine treatment. METHODS: The effect on brain activation of a single dose of rivastigmine was tested in seven patients with mild Alzheimer's disease using fMRI during face encoding, and in five patients during a parametric working memory task. RESULTS: During face encoding, rivastigmine increased bilateral activation in the fusiform gyrus. Brain activation was also enhanced in the prefrontal cortex in a simple working memory task. When working memory load was further increased, not only was increased activation seen, but in certain areas there was also decreased activation. CONCLUSIONS: These findings link the previously observed increase in cognitive performance in Alzheimer's disease after treatment with a cholinesterase inhibitor to altered brain activation. Although the results cannot be generalised to the Alzheimer's disease population at large, they provide evidence that in mild Alzheimer's disease, rivastigmine enhances brain activation in the fusiform and frontal cortices. This is compatible with the concept of cholinergic circuitry.

Aged↗
PubMed2002

CT and MRI rating of white matter lesions.

Rating scales play an important role in the evaluation of computed tomography (CT) or magnetic resonance-detected white matter lesions (WML). Unfortunately, this type of visual semiquantitative assessment is not yet an optimal tool because commonly agreed concepts regarding its use are lacking. To generate a discussion platform for further improvement of CT and MRI rating, we will provide some basic definitions, summarize the advantages and disadvantages of scoring schemes and review current efforts towards the improvement of this tool. Future research will have to concentrate on deepening our understanding of the histopathologic substrates of WML and on strategies to document their progression.

Aged↗
PubMed2002

Patterns of cerebral atrophy in dementia with Lewy bodies using voxel-based morphometry.

Previous cross-sectional MRI studies based on region-of-interest analyses have shown that increased cerebral atrophy is a feature of both Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Relative preservation of the hippocampus and temporal lobe structures in DLB compared to AD has been reported in region-of-interest-based studies. Recently, image processing techniques such as voxel-based morphometry (VBM) have been developed to provide an unbiased, visually informative, and comprehensive means of studying patterns of cerebral atrophy. We report the first study to use the voxel-based approach to assess patterns of cerebral atrophy in DLB compared to control subjects and AD. Regional gray matter volume loss was observed bilaterally in the temporal and frontal lobes and insular cortex of patients with DLB compared to control subjects. Comparison of dementia groups showed preservation of the medial temporal lobe, hippocampus, and amygdala in DLB relative to AD. Significant gray matter loss was also observed in the thalamus of AD patients compared to DLB.

Aged↗
PubMed2001

Effect of hydroxychloroquine on progression of dementia in early Alzheimer's disease: an 18-month randomised, double-blind, placebo-controlled study.

BACKGROUND: Results of epidemiological studies, neuropathological observations, and in-vitro experiments all suggest that inflammatory mechanisms contribute to the destructive lesions in Alzheimer's disease. We aimed to establish the effect of the anti-inflammatory drug hydroxychloroquine on the progression of dementia. METHODS: We did a double-blind, parallel-group, multicentre trial in which we randomly assigned 168 patients with early Alzheimer's disease to hydroxychloroquine (200 or 400 mg dependent on bodyweight), or placebo for 18 months. Outcome measures were related to activities of daily living, cognitive function, and behavioural abnormalities. Analysis was by intention to treat. RESULTS: At 18 months, mean scores for the interview for deterioration in daily life in dementia in patients on hydroxychloroquine (22.6 [SD 11.4]) did not differ from those for patients on placebo (21.3 [10.5]). Also, mean scores on the cognitive subscale of the Alzheimer's disease assessment scale were closely similar in hydroxychloroquine (26.4 [14.9]) and placebo (25.7 [14.3]) treated patients, as were behavioural changes, measured by the revised memory and behavioural problems checklist (36.3 [12.0] and 34.2 [12.4], respectively). Explorative analyses did not suggest any specific subgroup that benefited from hydroxychloroquine. The frequency and nature of serious adverse events and side-effects were much the same in both groups. 155 (92%) patients completed all assessments over the entire study. INTERPRETATION: Anti-inflammatory treatment with hydroxychloroquine for 18 months does not slow the rate of decline in minimal or mild Alzheimer's disease.

Activities of Daily Living↗
PubMed2001

Anterior medial temporal lobe activation during attempted retrieval of encoded visuospatial scenes: an event-related fMRI study.

Various studies have shown that the medial temporal lobe (MTL), which consists of the hippocampus and parahippocampal gyrus, is important for episodic memory. Earlier fMRI studies substantiated this role by showing activation upon encoding of visuospatial scenes. In this study we used event-related fMRI to study whether the cognitive process of retrieval of visuospatial scenes, tested with the use of a recognition paradigm, also activates the MTL. Nine subjects (mean age 24 years) were presented previously studied color pictures (old) and pictures they had never seen before (new) in a mixed trial design. Data analysis allowed calculation of the fMRI response of correct judgments on new pictures, old pictures, and false judgments. Since we used previously encoded color pictures as old stimuli, we also included an encoding paradigm in the current set of experiments. This allowed us to compare encoding and recognition activation in the MTL of exactly the same pictures in the same subjects. Correct judgments on new pictures showed an increased activation in the anterior parahippocampus bilaterally and the right anterior hippocampus compared to judgments on old pictures in the recognition experiment. The former judgments took significantly longer, indicating that retrieval of successfully stored information is less demanding than the effort to retrieve nonencoded information. A comparison of the two experimental data sets showed evidence for a functional segregation of encoding and retrieving color pictures. We conclude that the left posterior parahippocampal gyrus responds during encoding, while on the other hand the left anterior parahippocampal gyrus and the right anterior hippocampus were more strongly involved in retrieval.

Adult↗
PubMed2001

Functional MRI of visual cortex in sedated 18 month-old infants with or without periventricular leukomalacia.

Functional MRI (fMRI) of the visual cortex was evaluated in 42 sedated 18-month-old infants (mean corrected age; 31 males, 11 females) with or without periventricular leukomalacia (PVL). Data from 14 infants could not be evaluated because of movement artefacts. Ten of the remaining 28 infants showed no significant fMRI response upon visual stimulation. In 18 infants, a significant signal change upon stimulation was found in the visual cortex: in 17 a signal decrease and in one a signal increase. Functional changes were located mainly in the anterior part of the visual cortex. Seven of the 28 infants had normal MRI and 21 showed variable occipital PVL. An fMRI response was equally frequent in infants without PVL (4 of 7 infants) and with PVL (14 of 21 infants). In conclusion, fMRI was shown to be feasible in sedated infants. No correlation was found between functional activation and the presence or absence of occipital PVL. Type of fMRI response (signal decrease) and localization (anterior part of the visual cortex) are different from those seen in adults, probably reflecting a combination of sedation effects and immaturity of the visual system. At present, fMRI is a highly promising research tool; its clinical relevance still has to be established.

Case-Control Studies↗
PubMed2001

Temporal lobe rating scale: application to Alzheimer's disease and frontotemporal dementia.

OBJECTIVES: Temporal lobe atrophy as assessed by MRI can be measured in several ways. Volumetric measurements are quantitative but very time consuming and require extensive training to perform, so are not easily transferable to clinical practice. Visual rating scales, by contrast, are quick and widely applicable. Although medial temporal lobe atrophy is well described in Alzheimer's disease (AD), it is uncertain how early these changes can be detected and whether they discriminate AD from other neurodegenerative diseases, most notably frontotemporal dementia (FTD). The objectives were (1) to develop a widely applicable temporal lobe rating scale, and (2) to characterise and quantify the patterns of temporal lobe atrophy in AD versus temporal and frontal variants of FTD. METHODS: The temporal lobe assessments were made using an established hippocampal rating scale extended to incorporate additional temporal regions. This was firstly validated with volumetric analysis and then applied to 30 probable AD, 30 FTD (consisting of 17 temporal variant (semantic dementia) and 13 frontal variant) and 18 control coronal MRI images. RESULTS: Bilateral hippocampal atrophy was found in 50% of the patients with AD. Contrary to expectations, patients with semantic dementia also had hippocampal atrophy, which for the left side exceeded that seen in AD; other regions (temporal pole, parahippocampal gyrus, and lateral temporal lobe), spared in AD, were severely atrophied in this group. The patients with frontal variant FTD occupied an intermediate position and were largely indistinguishable from AD. CONCLUSIONS: Hippocampal atrophy is, therefore, not specific for AD. Semantic dementia can be distinguished from AD, by the presence of severe bilateral atrophy of the temporal pole, parahippocampal and lateral regions. These findings have implications for the differential diagnosis of dementias.

Aged↗
PubMed2001

A new rating scale for age-related white matter changes applicable to MRI and CT.

BACKGROUND AND PURPOSE: MRI is more sensitive than CT for detection of age-related white matter changes (ARWMC). Most rating scales estimate the degree and distribution of ARWMC either on CT or on MRI, and they differ in many aspects. This makes it difficult to compare CT and MRI studies. To be able to study the evolution and possible effect of drug treatment on ARWMC in large patient samples, it is necessary to have a rating scale constructed for both MRI and CT. We have developed and evaluated a new scale and studied ARWMC in a large number of patients examined with both MRI and CT. METHODS: Seventy-seven patients with ARWMC on either CT or MRI were recruited and a complementary examination (MRI or CT) performed. The patients came from 4 centers in Europe, and the scans were rated by 4 raters on 1 occasion with the new ARWMC rating scale. The interrater reliability was evaluated by using kappa statistics. The degree and distribution of ARWMC in CT and MRI scans were compared in different brain areas. RESULTS: Interrater reliability was good for MRI (kappa=0.67) and moderate for CT (kappa=0.48). MRI was superior in detection of small ARWMC, whereas larger lesions were detected equally well with both CT and MRI. In the parieto-occipital and infratentorial areas, MRI detected significantly more ARWMC than did CT. In the frontal area and basal ganglia, no differences between modalities were found. When a fluid-attenuated inversion recovery sequence was used, MRI detected significantly more lesions than CT in frontal and parieto-occipital areas. No differences were found in basal ganglia and infratentorial areas. CONCLUSIONS: We present a new ARWMC scale applicable to both CT and MRI that has almost equal sensitivity, except for certain regions. The interrater reliability was slightly better for MRI, as was the detectability of small lesions.

Aging↗
PubMed2001

Raloxifene affects brain activation patterns in postmenopausal women during visual encoding.

Recent brain imaging studies have shown that estrogens alter brain activation patterns upon working memory tasks in postmenopausal women. Estrogens, however, have many systemic side effects. We investigated the effect of the Selective estrogen receptor modulator (SERM) raloxifene on brain activation patterns during a memory task in postmenopausal women with functional magnetic resonance imaging (fMRI). Twenty postmenopausal and right handed women (mean age 65.7 years; SD 3.0) were included in this double blind, placebo controlled and randomized study. Whole brain fMRI was performed before and after three months of daily treatment with raloxifene 60 mg or placebo. Each scanning session consisted of a visual encoding task, a recognition test and a simple photic simulation test. Data analyses was performed with SPM99b software. Specific regions of interest for the tasks were defined based in previous experiments. Visual encoding activated the ventral route, posterior medial temporal lobe and frontal cortex in both groups. Treatment interactions for raloxifene compared to placebo were a decrease in activation in the left parahippocampal gyrus and left lingual gyrus, an increase in activation in the right superior frontal gyrus. The mean recognition test and the simple photic stimulation test showed no treatment interactions. Our results show that raloxifene affects brain activation patterns upon visual encoding in postmenopausal women.

Aged↗
PubMed2000

Unbiased whole-brain analysis of gray matter loss in Alzheimer's disease.

In patients with Alzheimer's disease, substantial tissue loss occurs in the medial temporal lobe. In this study, we applied a voxel-based, unbiased whole-brain analysis method to compare magnetic resonance imaging scans of seven patients with Alzheimer's disease and seven healthy elderly controls. Images were transformed to standard coordinate space and tested for gray matter loss in patients. We found symmetrical decreases of gray matter in patients in the hippocampus, and, unexpectedly, also in the head of the caudate nucleus and the insula. The exact role of these two structures in the symptomatology of Alzheimer's disease deserves further attention.

Aged↗
PubMed2000

FMRI of visual encoding: reproducibility of activation.

fMRI, a noninvasive technique to measure brain activation, is gaining clinical interest, because its sensitivity enables individual assessments. However, more insight in the reproducibility of these measurements during higher cognitive tasks is necessary. We performed an fMRI study involving within- and between-subject reproducibility during encoding of complex visual pictures. Ten healthy subjects were studied on three occasions: twice in the same scanning session (study 1 and 2), and a third time, 3-24 days later (study 3). On all 30 occasions but one, activation was found in areas expected on the basis of previous studies, including the fusiform and lingual gyri, occipital and parietal areas, the (para)hippocampal area, and the frontal inferior sulcus. The reproducibility of the number of activated voxels in the whole brain was 72% and 63% (respectively, studies 1 and 2, and 1 and 3). The reproducibility of anatomical identical pixels that supplement these results was 49% and 36%. These reproducibility measures increase about 5-15% when only areas of expected activation are included. The quantitative measurements indicate that there is substantial variation in the volume of activation. The recognition of pictures as tested afterward explains part of this variation between subjects. Our findings indicate that whereas consistent patterns of activation exist, more insight is needed into what determines the volume of activation, especially to assess cognitive alterations in patients over time.

Adult↗