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P Scheltens

Publications and source records attributed to P Scheltens.

At least 91 records · Page 5Linked to original sources
PubMed1999

Early diagnosis of dementia: neuroimaging.

The use of neuroimaging is reviewed in the diagnosis of dementia, especially Alzheimer's disease (AD). Computed tomography (CT) may be used to exclude other causes of dementia than AD. The finding of cortical or subcortical atrophy on CT or magnetic resonance imaging (MRI) itself does not indicate AD. Hippocampal atrophy on CT/MRI provides a useful early marker, although further longitudinal and neuropathological study is required. CT- and MRI-based measurements of hippocampal atrophy show promise in providing useful diagnostic information for discriminating patients with probable AD from normal elderly individuals. Using a standardized imaging protocol, including some assessment of hippocampal atrophy, can save costs since patients with suspected AD must undergo a cross-sectional imaging study to exclude other (treatable) causes of dementia. Combining an assessment of hippocampal atrophy with cerebral blood flow measurements by single photon emission computed tomography is not warranted either from a clinical or from an economic point of view.

Aged↗
PubMed1999

Medial temporal lobe atrophy and memory dysfunction as predictors for dementia in subjects with mild cognitive impairment.

To determine whether the medial temporal lobe is atrophic in subjects with mild cognitive impairment, and whether atrophy of this structure is a better predictor of dementia than memory dysfunction. Forty-five noninstitutionalized subjects aged 65-85 years were randomly selected from a population based study to obtain a sample with Alzheimer's disease (AD; n = 7), and a clinically nondemented sample (n = 38). Twenty of the latter subjects displayed some cognitive impairment and fulfilled CAMDEX criteria for "minimal dementia." Coronal T1-weighted magnetic resonance imaging was used to visualize the medial temporal lobe. The volume of the parahippocampal gyrus and hippocampus was measured, and medial temporal lobe atrophy was assessed qualitatively. The memory subscore from the CAMCOG was used as a measure of memory functioning. The follow-up period was 3 years. Nine subjects who were diagnosed as being minimally demented at baseline met the criteria for AD during follow-up. At baseline the volume of the parahippocampal gyrus of these subjects was smaller than that of the other subjects with minimal dementia. The memory score was the best predictor of clinical outcome. All medial temporal lobe measures increased the accuracy of prediction compared with only the memory score, by reducing the number of false-negative classifications of dementia. Severe medial temporal lobe atrophy is present even in some subjects with mild cognitive impairment and is an indicator of subsequent AD. The absence of medial temporal lobe atrophy, however, does not exclude the development of dementia. In the majority of subjects memory impairment was a better predictor of dementia than atrophy of the medial temporal lobe. The combination of the two increased predictive accuracy. Nondemented subjects with severe atrophy of the medial temporal lobe could be enrolled in drug trials aimed at slowing the progression of AD.

Aged↗
PubMed1999

The diagnostic value of electroencephalography in mild senile Alzheimer's disease.

OBJECTIVE: We investigated the diagnostic value of the visually assessed electroencephalogram (EEG) in patients with mild Alzheimer's disease (AD), using the grand total of EEG (GTE) score. METHODS: Forty-nine non-demented control subjects with and without minimal cognitive impairment from the general population and 86 probable AD patients (NINCDS-ADRDA criteria), consecutively referred to a memory clinic, participated in this study. RESULTS: Frequency of rhythmic background activity (P<0.05), diffuse slow activity (P<0.001), and reactivity of the rhythmic background activity (P<0.001) were statistically significant related to the diagnosis control subject or AD patient, using logistic regression analysis with adjustment for age and sex. When these subscores were used to confirm the diagnosis of AD, thus at high specificity of 89.1% (GTE cut-off point of 3), the sensitivity was 44.6% and positive predictive value was 88.1%. Incremental ruling-in and ruling-out curves showed a maximum diagnostic gain of 38% for a positive test result at a prior probability ranging from 30 to 40%. At high pretest probability levels of 80-90%, the diagnostic gain for a positive test result was low, varying from 7 to 14%. CONCLUSION: In conclusion, the visually assessed EEG may give a clinically meaningful contribution to the diagnostic evaluation of AD when there is diagnostic doubt.

Aged↗
PubMed1999

Magnetic resonance imaging differences between dementia with Lewy bodies and Alzheimer's disease: a pilot study.

BACKGROUND: Temporal lobe atrophy on magnetic resonance imaging (MRI) has been suggested as a specific diagnostic marker for Alzheimer's disease (AD). No previous comparison with dementia with Lewy bodies (DLB) has been reported. METHOD: T1-weighted MRI scans were performed on 11 subjects with AD (nine with NINCDS/ADRDA probable AD and two with neuropathologically proven AD) and nine subjects with DLB (four with probable DLB diagnosed by clinical criteria and five with neuropathologically proven DLB). Groups were matched for age, duration of illness and cognitive test score. Two raters, blind to diagnosis and neuropathological findings, measured the volumes of the frontal lobes, temporal lobes, hippocampi, parahippocampal gyri, amygdalae, and caudate nuclei using a computerized volumetric analysis system. Scans were also rated for medial temporal atrophy on a four-point scale by an experienced rater. RESULTS: AD subjects had significantly smaller left temporal lobes and parahippocampal gyri than those with DLB. Medial temporal atrophy was present in 9/11 AD cases (82%) and absent in 6/9 (67%) of DLB cases. Two neuropathologically confirmed cases of DLB had severe medial temporal atrophy; both had concurrent AD-type pathology in the temporal lobe (Braak stage 4). CONCLUSIONS: This pilot study supports the hypothesis that a greater burden of pathology centres on the temporal lobes in AD compared with DLB, except in DLB cases with concurrent Alzheimer pathology. A larger study is needed to confirm these findings and to determine whether MRI has a role in assisting with the clinical differentiation between DLB and AD.

Aged↗
PubMed1999

Neuropsychological correlates of a right unilateral lacunar thalamic infarction.

OBJECTIVES: To report on a patient with a lacunar infarction in the right intralaminar nuclei of the thalamus. The role of the thalamic intralaminar nuclei in cognitive function is as yet insufficiently known. The patient described has shown signs of apathy and loss of initiative, in combination with cognitive deficits, which have persisted essentially unaltered up to the present day since an abrupt onset 17 years ago. METHODS: High resolution MRI was performed to show the extent of the lesion; a combination of published and experimental neuropsychological techniques was administered to show the nature of the cognitive defects; Single photon emission computed tomography (SPECT) was employed to obtain a measure of cortical perfusion. RESULTS: Brain MRI disclosed an isolated lacunar infarction in the dorsal caudal intralaminar nuclei of the thalamus. Neuropsychological evaluation indicated problems with attention and concentration, executive disturbances, and memory deficits both in the visual and verbal domains. The memory deficits could not be attributed to problems in the early stages of information processing, and are hence regarded as resulting from a failure of retrieval rather than encoding or storage. Brain SPECT disclosed a hypoperfusion of the right frontal cortex. CONCLUSION: The data indicate that the cognitive profile is the result of a dysfunction of executive functions. This is corroborated by the finding of decreased blood flow in the right frontal cortex, and by evidence from the neuroanatomical literature. Thus the dysexecutive symptoms are thought to be caused by disconnection of the prefrontal cortex from the brainstem activating nuclei through the strategic localisation of the right thalamic infarction.

Adult↗
PubMed1999

White matter lesions on magnetic resonance imaging in dementia with Lewy bodies, Alzheimer's disease, vascular dementia, and normal aging.

OBJECTIVES: Alzheimer's disease and vascular dementia are associated with an increase in changes in white matter on MRI. The aims were to investigate whether white matter changes also occur in dementia with Lewy bodies and to examine the relation between white matter lesions and the cognitive and non-cognitive features of dementia with Lewy bodies, Alzheimer's disease, and vascular dementia. METHODS: Proton density and T2 weighted images were obtained on a 1.0 Tesla MRI scanner in patients with dementia with Lewy bodies (consensus criteria; n=27, mean age=75.9 years), Alzheimer's disease (NINCDS/ADRDA; n=28, mean age=77.4 years), vascular dementia (NINDS/AIREN; n=25, mean age=76.8 years), and normal controls (n=26, mean age=76.2 years). Cognitive function, depressive symptoms, and psychotic features were assessed using a standardised protocol. Periventricular hyperintensities (PVHs), white matter hyperintensities (WMHs) and basal ganglia hyperintensities (BGHs) were visually rated blind to diagnosis using a semiquantitative scale. RESULTS: Periventricular hyperintensities were positively correlated with age and were more severe in all dementia groups than controls. Total deep hyperintensities scores (WMHs plus BGHs) were significantly higher in all dementia groups than controls and higher in patients with vascular dementia than those with dementia with Lewy bodies or Alzheimer's disease. In all patients with dementia, frontal WMHs were associated with higher depression scores and occipital WMHs were associated with an absence of visual hallucinations and delusions. CONCLUSION: In common with Alzheimer's disease and vascular dementia, PVHs and WMHs were significantly more extensive in dementia with Lewy bodies than in controls. This overlap between different dementias may reflect shared pathological mechanisms. The link between frontal WMHs and depression and the absence of occipital WMHs and psychotic symptoms has important implications for understanding the neurobiological basis of these symptoms.

Aged↗
PubMed1998

[Cholinesterase inhibitors for Alzheimer disease: preliminary recommendations for treatment. Dutch Society for Psychiatry, Section of Geriatric Psychiatry].

Several cholinesterase inhibitors have recently become available for Alzheimer's disease. To reach consensus about their relevance and use in daily practice, a meeting with clinical experts was organised by the section of Geriatric Psychiatry of the Dutch Society for Psychiatry. So far, available drugs have only very modest effects on cognitive functioning and clinical impression, compared with placebo. The question whether these effects are clinically relevant cannot be answered yet. Awaiting the results of further studies, it was decided not to use cholinesterase inhibitors on a routine basis but to limit prescription of these drugs to research setting or under well-controlled conditions with regard to diagnosis and evaluation. Furthermore, prescription must be limited to mild or moderately severe dementia caused by 'probable Alzheimer's disease'. Proper evaluation in the individual patient is still an unresolved problem. Therefore, n = I protocols are to be designed. These should include the use of appropriate and standardised instruments measuring cognitive functions, behavioural functions and activities of daily life. The skills and experience required will be available in specialised and multidisciplinary units for dementia. Pharmaceutical treatment for Alzheimer's disease must be integrated with all other available forms of patient care.

Aged↗
PubMed1998

The influence of coincidental vascular pathology on symptomatology and course of Alzheimer's disease.

The aim of this review is to determine the influence of coincidental cerebrovascular pathology on the symptomatology and course of Alzheimer's disease (AD). The link between stroke and AD is probably higher than expected by chance for the following reasons: (i) both pathologies share genetic risk factors such as the epsilon 4 allele of the apolipoprotein E gene; (ii) AD patients have changes in the brain vessels that may lead to either ischemic or hemorrhagic stroke or white matter changes or both; (iii) there is evidence of an increased risk of stroke in AD patients; (iv) there is evidence of a frequent association of AD and stroke at autopsy. Because of the summation of the various types of lesions, stroke lesions may lead to an increase progression of cognitive decline in AD patients. Recognition of a vascular component in a dementia syndrome is therefore useful for the management of AD patients. Whether an optimal management of risk factors for stroke may delay the clinical expression of dementia in patients with preclinical Alzheimer pathology should be evaluated.

Alzheimer Disease↗
PubMed1998

Within-subject reproducibility of visual activation patterns with functional magnetic resonance imaging using multislice echo planar imaging.

Within-subject reproducibility of visual brain activation using multislice echo planar functional magnetic resonance imaging (fMRI) was tested. Ten healthy subjects underwent fMRI with visual stimulation on three occasions: two studies in one scanning session (without repositioning); and a third study 1 h to 2 weeks later. Following a three-dimensional matching procedure, activation was measured and compared between sessions on a voxel-by-voxel basis. Data were filtered to full-width-at-half-maximum of 4.0 x 4.0 x 5.0 mm and a conservative Bonferroni-corrected significance threshold was applied to correlation maps. For reproducibility, change in centre of mass of the activated volume, a ratio of the number of pixels and a ratio of the number of overlapping pixels was calculated. Further, reproducibility was tested varying significance thresholds and at different filter widths. Average changes in centre of mass of the activated volume were 2.63 and 3.96 mm between Studies 1 and 2 and 1 and 3, respectively. The reproducibility of the number of activated voxels was 90% and 88% (Studies 1 and 2 and 1 and 3). The ratio of overlapping pixels was 74% between Studies 1 and 2 and 64% between Studies 1 and 3. Varying the significance threshold showed that at a certain range, the overlap reached a maximum, and increasing the filter widths increased reproducibility. It is concluded that fMRI with visual stimulation can be used to measure brain activity with reasonably good reproducibility on a routine clinical system equipped with echo planar imaging. Difficulties remain in separating the contribution of motion, repositioning errors, and true physiological changes.

Adolescent↗
PubMed1998

Brain and spinal cord abnormalities in multiple sclerosis. Correlation between MRI parameters, clinical subtypes and symptoms.

We investigated various magnetic resonance MRI parameters for both brain and spinal cord to see if any improved the clinicoradiological correlation in multiple sclerosis. Ninety-one multiple sclerosis patients (28 relapsing-remitting, 32 secondary progressive and 31 primary progressive) were imaged using conventional T1, proton density- and T2-weighted MRI of the brain and spinal cord. Focal brain and spinal cord lesion load was scored, as were diffuse signal abnormalities, brain ventricular volume and spinal cord cross-sectional area. Clinical measures included the expanded disability status scale (EDSS), the functional systems score and a dedicated urology complaint questionnaire. Secondary progressive patients differed from relapsing-remitting and primary progressive patients by a larger number of hypointense T1 lesions in the brain, ventricular enlargement and spinal cord atrophy. Primary progressive patients more often had diffuse abnormalities in the brain and/or spinal cord than did relapsing-remitting and secondary progressive patients. In the entire study population, EDSS correlated with both brain and spinal cord MRI parameters, which were independent. The urological complaint score correlated only with spinal cord MRI parameters. In relapsing-remitting and secondary progressive multiple sclerosis, the correlation between MRI and clinical parameters was better than in the entire population. In this subgroup EDSS variance could be explained best by T1 brain lesion load, ventricle volume and spinal cord cross-sectional area. In the primary progressive subgroup the clinicoradiological correlation was weak for brain parameters but was present between spinal cord symptoms and spinal cord MRI parameters. In conclusion, the different brain and spinal cord MRI parameters currently available revealed considerable heterogeneity between clinical subtypes of multiple sclerosis. In relapsing-remitting and secondary progressive multiple sclerosis both brain and spinal cord MRI may provide a tool for monitoring patients, while in primary progressive multiple sclerosis the clinicoradiological correlation is weak for brain imaging.

Adult↗
PubMed1998

White matter changes on CT and MRI: an overview of visual rating scales. European Task Force on Age-Related White Matter Changes.

Since the recognition of white matter changes on CT (leukoaraiosis), rating scales for the location and severity of white matter changes have been developed, mainly for research purposes, to investigate factors such as the relation with cognition, risk factors, and pathology. The main purpose of rating scales is to provide scores that can be used in statistical analyses. The development of the NINDS-AIREN criteria for vascular dementia have introduced a new application for these rating scales in investigating and delineating the amount of white matter changes on CT/MRI sufficient to fulfill the criteria. Furthermore, in Alzheimer's disease, recognition of white matter changes may serve to delineate homogeneous groups and help to identify patients with different symptomatology. We reviewed the existing rating scales for CT and MRI and judged their properties and reliability. The ideal rating scale does not yet exist, but different rating scales may serve different purposes, for which some recommendations are made.

Brain Ischemia↗
PubMed1998

Pathophysiologic mechanisms in the development of age-related white matter changes of the brain.

Magnetic resonance imaging (MRI) has dramatically enhanced our capability of detecting age-related changes of the brain even before they become clinically apparent. Among those are preferentially alterations of the white matter in periventricular, deep and subcortical locations which display high signal intensity on both proton density- and T2-weighted images. Correlative histopathologic findings show hyperintense periventricular capping of the frontal horns to reflect predominantly a specific anatomic situation characterized by loosely arranged fine-fiber tracts with low myelin and high extracellular fluid content. A smooth halo of periventricular hyperintensity has been linked to disruption of the ependymal lining with subependymal gliosis and concomitant loss of myelin. In contrast, punctate, early confluent and confluent hyperintensities in the deep and subcortical white matter as well as irregular periventricular hyperintensity appear to be of vascular origin. Punctate lesions tend to correspond to a perivascular reduction in myelin content with atrophy of the neuropil and seem to constitute a negligible extent of tissue damage from low permeability through thickened arteriolar walls. Early confluent and confluent hyperintensities, however, indicate more extensive ischemic damage consistent with advanced microangiopathy.

Aging↗
PubMed1998

Histopathologic correlate of hypointense lesions on T1-weighted spin-echo MRI in multiple sclerosis.

Postmortem unfixed whole brains from five multiple sclerosis (MS) patients were examined by MRI using a T2- and T1-weighted spin-echo (SE) sequence and histology to investigate the histopathologic characteristics of hypointense lesions on T1-weighted SE MR images. The degree of hypointensity was scored semiquantitatively by two blinded observers in reference to normal-appearing white matter. Signal intensities of the lesions and the normal-appearing white matter were measured to obtain contrast ratios. Hematoxylin-eosin stain was used to assess degree of matrix destruction (decrease of density of the neuropil) and cellularity of a lesion, Klüver-Barrera stain for degree of demyelination, Bodian stain for axonal density, and immunostaining of glial fibrillary acid protein for reactive astrocytes and fibrillary gliosis. Nineteen lesions were selected for analysis. Nearly all lesions were compatible with the chronic MS plaque: hypocellularity, absence of myelinated axons, in the presence of reactive astrocytes. Contrast ratios of the lesions were highly correlated (R = -0.90; p < 0.01), with degree of hypointensity scored semiquantitatively. Degree of hypointensity on T1-weighted SE images did not correlate with degree of demyelination or number of reactive astrocytes, but was associated with axonal density (R = -0.71; p = 0.001). A trend was found with degree of matrix destruction (R = 0.45; p = 0.052). We conclude that, in our limited sample, hypointense lesions seen on T1-weighted SE MR images are associated histopathologically with severe tissue destruction, including axonal loss. Our results need to be substantiated in a larger study on more varied patient material to evaluate the use of hypointense lesions as a surrogate marker of persistent deficit in MS patients.

Adult↗
PubMed1998

Familial aggregation in frontotemporal dementia.

OBJECTIVE AND BACKGROUND: Frontotemporal dementia (FTD) is a common, non-Alzheimer's dementia. Its familial occurrence has been reported, but the frequency of positive family history is unknown. METHODS: We carried out a nationwide genetic-epidemiologic study of FTD in the Dutch population of 15 million people. The family history of dementia was analyzed in 74 FTD patients and 561 age- and gender-matched control subjects. RESULTS: We found one or more first-degree relatives with dementia before age 80 in 38% (28 of 74) of FTD patients, but only in 15% (84 of 561) of control subjects. Ten percent of FTD patients had two or more first-degree relatives with dementia compared with 0.9% of the control subjects. Seven percent of FTD patients showed the ApoE4E4 genotype versus 2.3% of the control subjects. The first-degree relatives of FTD had a risk of 22% for dementia before age 80 compared with 11% in relatives of control subjects. The age of onset of dementia in affected first-degree relatives of FTD patients (60.9+/-10.6 years) was significantly lower than among affected relatives of control subjects (72.3+/-8.5 years). The first-degree relatives of FTD patients were 3.5 times (95% CI, 2.4 to 5.2) more at risk for developing dementia before age 80 than relatives of control subjects. The hazard ratio in the subgroup with unknown linkage to chromosome 17 was 2.4 (95% CI, 1.5 to 3.7). CONCLUSION: This study documents the importance of genetic factors in a proportion of FTD patients with the age at onset of dementia in first-degree relatives being 11 years earlier than in the general population.

Adult↗
PubMed1998

Visual activation patterns in patients with optic neuritis: an fMRI pilot study.

We studied the use of functional MRI (fMRI) with visual stimulation in nine patients with unilateral optic neuritis. Eight healthy subjects served as controls. Patients showed reduced activation upon stimulation of the affected eye, on average 33% (range 0 to 156%) of the average monocular activation in the control group. Decreased activation was also seen for the unaffected eye (61% of control values, range 3 to 133%). We conclude that fMRI with visual stimulation is feasible in patients with optic neuritis and deserves future study.

Adult↗
PubMed1998

Early diagnostic indices for the prevention of Alzheimer's disease.

Recent progress in our understanding of the pathophysiology of Alzheimer's disease (AD) has made it clear that it is a heterogeneous disorder to which both genetic and environmental factors contribute. Therefore, it is unlikely that a single test for the diagnosis of this disease will be developed. Possible candidates for early diagnostic indices have been identified, in addition to biological markers, in the fields of neuropsychology, genetics and neuroimaging. Many studies have indicated that low scores in tests assessing delayed recall predict dementia already years before the actual criteria of dementia are fulfilled. Molecular genetic studies have confirmed that the epsilon4 allele of the apolipoprotein E (APOE) is also a definite risk factor for AD, and other susceptibility genes will probably be identified and confirmed in the near future. Evaluation of the hippocampal atrophy by magnetic resonance imaging (MRI) scans has been reported to be a sensitive and possible specific indicator of mild AD, while possibilities of using functional MRI are currently being explored. A combination of low scores in tests assessing delayed recall, small size of the hippocampus on MRI and APOE epsilon4 might point to a high risk of developing AD. We need extensive follow-up studies to identify which combination of molecular genetic factors and memory test scores supplemented with neuroimaging will prove to be most efficient in diagnosing AD in its preclinical phase, as this is the phase which offers the most promising therapeutic options.

Alzheimer Disease↗