Search PubMed⌕ Search

Biomedical subjects

P Scheltens

Publications and source records attributed to P Scheltens.

At least 37 records · Page 2Linked to original sources
PubMed2005

Multicenter assessment of reliability of cranial MRI.

Clinical utility of magnetic resonance imaging (MRI) for the diagnosis and assessment of neurodegenerative diseases may depend upon the reliability of MRI measurements, especially when applied within a multicenter context. In the present study, we assessed the reliability of MRI through a phantom test at a total of eleven clinics. Performance and entry criteria were defined liberally in order to support generalizability of the results. For manual hippocampal volumetry, automatic segmentation of brain compartments and voxel-based morphometry, multicenter variability was assessed on the basis of MRIs of a single subject scanned at ten of the eleven sites. In addition, cranial MRI scans obtained from 73 patients with Alzheimer's disease (AD) and 76 patients with mild cognitive impairment were collected at subset of six centers to assess differences in grey matter volume. Results show that nine out of eleven centers tested met the reliability criteria of the phantom test, where two centers showed aberrations in spatial resolution, slice thickness and slice position. The coefficient of variation was 3.55% for hippocampus volumetry, 5.02% for grey matter, 4.87% for white matter and 4.66% for cerebrospinal fluid (CSF). The coefficient of variation was 12.81% (S.D.=9.06) for the voxel intensities within grey matter and 8.19% (S.D.=6.9) within white matter. Power analysis for the detection of a difference in the volumes of grey matter between AD and MCI patients across centers (d=0.42) showed that the total sample size needed is N=180. In conclusion, despite minimal inclusion criteria, the reliability of MRI across centers was relatively good.

Adult↗
PubMed2005

Consensus paper of the WFSBP Task Force on Biological Markers of Dementia: the role of CSF and blood analysis in the early and differential diagnosis of dementia.

Aging of population, and increasing life expectancy result in an increasing number of patients with dementia. This symptom can be a part of a completely curable disease of the central nervous system (e.g, neuroinflammation), or a disease currently considered irreversible (e.g, Alzheimer's disease, AD). In the latter case, several potentially successful treatment approaches are being tested now, demanding reasonable standards of pre-mortem diagnosis. Cerebrospinal fluid and serum analysis (CSF/serum analysis), whereas routinely performed in neuroinflammatory diseases, still requires standardization to be used as an aid to the clinically based diagnosis of AD. Several AD-related CSF parameters (total tau, phosphorylated forms of tau, Abeta peptides, ApoE genotype, p97, etc.) tested separately or in a combination provide sensitivity and specificity in the range of 85%, the figure commonly expected from a good diagnostic tool. In this review, recently published reports regarding progress in neurochemical pre-mortem diagnosis of dementias are discussed with a focus on an early and differential diagnosis of AD. Novel perspectives offered by recently introduced technologies, e.g, fluorescence correlation spectroscopy (FCS) and surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) are briefly discussed.

Aged↗
PubMed2005

Do MCI criteria in drug trials accurately identify subjects with predementia Alzheimer's disease?

BACKGROUND: Drugs effective in Alzheimer-type dementia have been tested in subjects with mild cognitive impairment (MCI) because these are supposed to have Alzheimer's disease in the predementia stage. OBJECTIVES: To investigate whether MCI criteria used in these drug trials can accurately diagnose subjects with predementia Alzheimer's disease. METHODS: MCI criteria of the Gal-Int 11 study, InDDEx study, ADCS memory impairment study, ampakine CX 516 study, piracetam study, and Merck rofecoxib study were applied retrospectively in a cohort of 150 non-demented subjects from a memory clinic. Forty two had progressed to Alzheimer type dementia during a five year follow up period and were considered to have predementia Alzheimer's disease at baseline. Outcome measures were the odds ratio, sensitivity, specificity, and positive and negative predictive value. RESULTS: The odds ratio of the MCI criteria for predementia Alzheimer's disease varied between 0.84 and 11. Sensitivity varied between 0.46 and 0.83 and positive predictive value between 0.43 and 0.76. None of the criteria combined a high sensitivity with a high positive predictive value. Exclusion criteria for depression led to an increase in positive predictive value and specificity at the cost of sensitivity. In subjects older than 65 years the positive predictive value was higher than in younger subjects. CONCLUSIONS: The diagnostic accuracy of MCI criteria used in trials for predementia Alzheimer's disease is low to moderate. Their use may lead to inclusion of many patients who do not have predementia Alzheimer's disease or to exclusion of many who do. Subjects with moderately severe depression should not be excluded from trials in order not to reduce the sensitivity.

Aged↗
PubMed2005

Progression of cerebral white matter lesions in Alzheimer's disease: a new window for therapy?

BACKGROUND: White matter lesions (WML) are a risk factor for Alzheimer's disease. Progression of WML is associated with vascular factors and cognitive decline in population based studies but the course of WML is unknown in Alzheimer's disease. OBJECTIVE: To investigate the prevalence and risk factors for progression of WML in Alzheimer's disease. SUBJECTS: 38 patients with Alzheimer's disease for whom blood pressure measurements and sequential brain MRIs were available. METHODS: The proportion of patients with progression of WML was calculated, stratified on baseline absence or presence of WML by analysis of variance. Odds ratios (OR) were calculated by age and sex adjusted logistic regression to quantify the relation between blood pressure and progression of WML. RESULTS: About 25% of the patients showed progression of WML. Patients with WML at baseline had significantly more progression than those without WML at baseline (adjusted mean difference = 1.2; 95% confidence interval (CI), 0.6 to 1.8). Diastolic blood pressure (DBP) was particularly related to progression of WML (OR = 5.9 (95% CI, 1.0 to 37.6) per 10 mm Hg DBP, p = 0.05). CONCLUSIONS: Alzheimer's disease patients with WML at baseline are at risk for rapid progression of WML. WML may offer a potential treatment target in this disease to ameliorate the rate of cognitive decline.

Aged↗
PubMed2005

Medial temporal lobe atrophy and white matter hyperintensities are associated with mild cognitive deficits in non-disabled elderly people: the LADIS study.

OBJECTIVE: To assess the associations of medial temporal lobe atrophy (MTA) and white matter hyperintensities (WMH) with cognitive function in a large group of independently functioning elderly people. METHODS: Data were drawn from the multicentre, multinational leukoaraiosis and disability (LADIS) project which is studying prospectively the role of WMH as an independent predictor of the transition to disability in non-disabled elderly people. In all, 639 participants were enrolled in the LADIS study. For the present analysis, data on 581 subjects were available. Cognitive function was assessed by the mini-mental state examination (MMSE). Visual ratings of WMH and MTA were undertaken on magnetic resonance images (MRI). RESULTS: The presence of either severe WMH or MTA was associated with a modest but non-significant increase in frequency of mild cognitive deficits (severe WMH: odds ratio (OR) = 1.9 (95% confidence interval (CI), 1.0 to 3.7); MTA present: OR = 1.5 (95% CI, 0.8 to 2.8)). However, subjects with the combination of MTA and severe WMH had a more than fourfold increase in frequency of mild cognitive deficits (OR = 4.1 (95% CI, 2.3 to 7.4)). Analysis of variance with post hoc Bonferroni t tests showed that subjects with both MTA and severe WMH performed worse on MMSE than those with either no MRI abnormality or a single MRI abnormality (p<0.05). CONCLUSIONS: These results provide further evidence for the combined involvement of both Alzheimer type pathology and vascular pathology in the earliest stages of cognitive decline and suggest an additive effect of WMH and MTA.

Aged↗
PubMed2004

Regional distribution of white matter hyperintensities in vascular dementia, Alzheimer's disease and healthy aging.

BACKGROUND: White matter hyperintensities (WMH) on MRI scans indicate lesions of the subcortical fiber system. The regional distribution of WMH may be related to their pathophysiology and clinical effect in vascular dementia (VaD), Alzheimer's disease (AD) and healthy aging. METHODS: Regional WMH volumes were measured in MRI scans of 20 VaD patients, 25 AD patients and 22 healthy elderly subjects using FLAIR sequences and surface reconstructions from a three-dimensional MRI sequence. RESULTS: The intraclass correlation coefficient for interrater reliability of WMH volume measurements ranged between 0.99 in the frontal and 0.72 in the occipital lobe. For each cerebral lobe, the WMH index, i.e. WMH volume divided by lobar volume, was highest in VaD and lowest in healthy controls. Within each group, the WMH index was higher in frontal and parietal lobes than in occipital and temporal lobes. Total WMH index and WMH indices in the frontal lobe correlated significantly with the MMSE score in VaD. Category fluency correlated with the frontal lobe WMH index in AD, while drawing performance correlated with parietal and temporal lobe WMH indices in VaD. CONCLUSIONS: A similar regional distribution of WMH between the three groups suggests a common (vascular) pathogenic factor leading to WMH in patients and controls. Our findings underscore the potential of regional WMH volumetry to determine correlations between subcortical pathology and cognitive impairment.

Aged↗
PubMed2004

Measuring progression of cerebral white matter lesions on MRI: visual rating and volumetrics.

OBJECTIVE: To evaluate the concordance of a volumetric method for measuring white matter lesion (WML) change with visual rating scales. METHODS: The authors selected a stratified sample of 20 elderly people (mean age 72 years, range 61 to 88 years) with an MRI examination at baseline and at 3-year follow-up from the community-based Rotterdam Scan Study (RSS). Four raters assessed WML change with four different visual rating scales: the Fazekas scale, the Scheltens scale, the RSS scale, and a new visual rating scale that was designed to measure change in WML. The authors assessed concordance with a volumetric method with scatter plots and correlations, and interobserver agreement with intraclass correlation coefficients. RESULTS: For assessment of change in WML, the Fazekas, Scheltens, and periventricular part of the RSS scale showed little correlation with volumetrics, and low interobserver agreement. The authors' new WML change scale and the subcortical part of the RSS scale showed good correlation with volumetrics. After additional training, the new WML change scale showed good interobserver agreement for measuring WML change. CONCLUSIONS: Commonly used visual rating scales are not well suited for measuring change in white matter lesion severity. The authors' new white matter lesion change scale is more accurate and precise, and may be of use in studies focusing on progression of white matter lesions.

Aged↗
PubMed2004

Behavioral symptoms in mild cognitive impairment.

The authors investigated neuropsychiatric symptoms in mild cognitive impairment (MCI) from baseline data of the Investigation in the Delay to Diagnosis of AD with Exelon (InDDEx) study (n = 1,010). Neuropsychiatric symptoms were reported in 59% of subjects (Neuropsychiatric Inventory [NPI]). NPI+ subjects had significantly greater impairment on global, cognitive, and functional scores than NPI- subjects. The presence of neuropsychiatric symptoms appears to be a marker of MCI severity.

Aged↗
PubMed2004

Global and local gray matter loss in mild cognitive impairment and Alzheimer's disease.

PURPOSE: Mild cognitive impairment (MCI) is thought to be the prodromal phase to Alzheimer's disease (AD). We analyzed patterns of gray matter (GM) loss to examine what characterizes MCI and what determines the difference with AD. MATERIALS AND METHODS: Thirty-three subjects with AD, 14 normal elderly controls (NCLR), and 22 amnestic MCI subjects were included and underwent brain MR imaging. Global GM volume was assessed using segmentation and local GM volume was assessed using voxel-based morphometry (VBM); VBM was optimized for template mismatch and statistical mass. RESULTS: AD subjects had significantly (12.3%) lower mean global GM volume when compared to controls (517 +/- 58 vs. 590 +/- 52 ml; P < 0.001). Global GM volume in the MCI group (552 +/- 52) was intermediate between these two: 6.2% lower than AD and 6.5% higher than the controls but not significantly different from either group. VBM showed that subjects with MCI had significant local reductions in gray matter in the medial temporal lobe (MTL), the insula, and thalamus compared to NCLR subjects. By contrast, when compared to subjects with AD, MCI subjects had more GM in the parietal association areas and the anterior and the posterior cingulate. CONCLUSION: GM loss in the MTL characterizes MCI, while GM loss in the parietal and cingulate cortices might be a feature of AD.

Aged↗
PubMed2004

The seven minute screen: a neurocognitive screening test highly sensitive to various types of dementia.

BACKGROUND: The seven minute screen (7MS) is a compilation of the temporal orientation test, enhanced cued recall, clock drawing, and verbal fluency. It has been shown to be useful for detecting Alzheimer's disease in a population of patients with memory complaints. OBJECTIVE: To assess the predictive validity of the 7MS for various types of dementia, and the influence of depression and other psychiatric conditions on 7MS scores. SETTING: Multicentre: secondary referral sites across the Netherlands. SUBJECTS: 542 patients with various types of dementia or depression, together with 45 healthy controls. RESULTS: Alzheimer's disease was diagnosed in 177 patients, other types of dementia in 164. The sensitivity of the 7MS for Alzheimer's disease was 92.9% with a specificity of 93.5%. For other types of dementia the sensitivity was 89.4% and the specificity 93.5%. Cognitive abnormalities were found in 71% of the patients with depression (n = 31). The mean (SD) duration of administration of the 7MS was 12.4 (4.6) minutes, range 8 to 22, depending on dementia severity. CONCLUSIONS: The 7MS is a useful screening tool for discriminating patients with dementia from cognitively intact patients. This not only applies to Alzheimer's disease but also to other types of dementia. Specificity with respect to depression was lower for the 7MS than for the MMSE.

Aged↗
PubMed2004

Alzheimer's disease--one clinical syndrome, two radiological expressions: a study on blood pressure.

BACKGROUND: Vascular risk factors could play a role in the aetiology of Alzheimer's disease, but this has not been investigated in relation to neuroimaging findings OBJECTIVE: To evaluate the distribution of blood pressure and an indicator of atherosclerosis (pulse pressure) in patients with Alzheimer's disease with and without small vessel disease. METHODS: 152 Alzheimer patients underwent 1.0T MRI scanning. Blood pressure was measured with a sphygmomanometer. Small vessel disease was assessed by the presence of lacunar infarcts and white matter lesions. The distribution of blood pressure and pulse pressure, with or without small vessel disease, was assessed by linear regression analysis. RESULTS: Patients with small vessel disease had a higher blood pressure, a wider pulse pressure, and an increased prevalence of hypertension. These findings were strongly age dependent: for patients under 65, mean systolic blood pressure was higher in the subpopulation with small vessel disease than in those without (mean (SD): 149.9 (19.3) v 135.7 (20.5) mm Hg; p = 0.02). Hypertension was more common in patients with white matter lesions than in those without (75.6% v 45.1%; p = 0.03) and the pulse pressure was higher (61.9 (14.4) v 51.7 (11.5) mm Hg; p = 0.01). There was no relation between blood pressure and the degree of (sub)cortical and hippocampal atrophy in patients without small vessel disease. CONCLUSIONS: There was heterogeneity in Alzheimer's disease patients with respect to blood pressure and pulse pressure. Alzheimer's disease encompasses a heterogeneous group of disorders which share a common cognitive profile but with distinct radiological features with respect to white matter lesions.

Age Factors↗
PubMed2003

Loss of frontal fMRI activation in early frontotemporal dementia compared to early AD.

OBJECTIVE: To compare frontal cortex activation in patients with early frontotemporal dementia (FTD) with that in patients with early AD. METHODS: Seven patients with FTD and seven patients with AD were studied (Clinical Dementia Rating: four patients with FTD 0.5, three patients with FTD 1, all patients with AD 1; mean Mini-Mental State Examination score: FTD 28.0 +/- 2.1, AD 23.1 +/- 2.7). Cerebral atrophy on MRI was mild, with no differences between FTD and AD. A parametric working memory task was applied to assess frontal activation as a function of working memory load. RESULTS: The activated working memory network in FTD and AD included frontal and parietal lobe and thalamus. In frontal and parietal cortex, brain activation was significantly decreased in FTD. Frontal regions in patients with FTD showed less linear activation increase with working memory load than in AD. Possibly as a compensation mechanism, the cerebellum showed a stronger increasing response in FTD. CONCLUSIONS: These data on regional functional loss in the frontal cortex in early FTD suggest that fMRI can identify FTD when results on structural MRI are normal.

Aged↗
PubMed2003

Decreased lysophosphatidylcholine/phosphatidylcholine ratio in cerebrospinal fluid in Alzheimer's disease.

Choline containing phospholipids are essential for the integrity of the'cell'membrane. Minor changes in the lysophosphatidylcholine (lyso-PC)/phosphatidylcholine (PC) ratio may lead to neuronal damage and cell loss. Several studies have shown protein and lipid oxidation in Alzheimer's disease (AD) affected brain regions. Amyloid-beta peptides may induce free-radical oxidative stress which normally is counteracted by anti-oxidant defense mechanisms. We hypothesize that oxidation may lead to changed concentrations of choline containing phospholipids in cerebrospinal fluid (CSF) of AD patients, because of the susceptibility of the unsaturated acyl-chains of PC for oxidation. PC and lyso-PC were determined in CSF of AD patients (n=19) and subjects with subjective memory complaints without dementia (n=19) by tandem mass spectrometry. No differences in total PC concentrations were observed between both study groups. Furthermore, we could not demonstrate different concentrations of PC species containing linoleic acid and PC species containing arachidonic acid. Interestingly, lyso-PC concentrations tended to be lower while the lyso-PC/PC ratio was significantly decreased in CSF of AD patients compared to controls (0.36% versus 0.54%; P=0.017). A comparable decrease was found for the lyso-PC/PC ratio for PC containing linoleic acid (P=0.022) or arachidonic acid (P=0.010), respectively. The lower lyso-PC/PC ratio in CSF of patients with AD may reflect alterations in the metabolism of choline-containing phospholipids in the brain in AD, and suggests that PC species containing linoleic acid or arachidonic acid are equally involved.

Alzheimer Disease↗