Ph Scheltens
Research interests
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Interestsnoncognitive neurological signs, Dementia, Biomarkers, MRI, PET imaging, White Matter
Publications
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8.17Impact points
Incidence of cerebral microbleeds: a longitudinal study in a memory clinic population.
Neurology. 06/2010; 74(24):1954-60.
Cerebral microbleeds (MBs) are commonly observed in memory clinic patients. Little is known about occurrence of and risk factors for developing new MBs in this population. To investigate incidence of lobar and nonlobar MBs in a memory clinic population. Furthermore, to assess risk factors for the de... [more] Cerebral microbleeds (MBs) are commonly observed in memory clinic patients. Little is known about occurrence of and risk factors for developing new MBs in this population. To investigate incidence of lobar and nonlobar MBs in a memory clinic population. Furthermore, to assess risk factors for the development of new MBs and their associations with other MRI changes. A total of 254 patients visiting our memory clinic, with repeat gradient-recalled echo T2*-weighted MRI, were included (scan interval 1.9 +/- 0.9 years). Baseline and incident MBs were regionally counted. White matter hyperintensities (WMH) and progression of WMH were assessed using visual rating scales. Baseline brain volume and whole-brain atrophy rate were estimated automatically. In a subset, APOE was determined. Thirty-one (12%) patients developed new MBs (range 1-19). Both multiple strictly lobar and nonlobar MBs at baseline predicted incident MBs (odds ratio [OR] 8.4; 95% confidence interval [CI] 2.2-33.2, and OR 33.8; 95% CI 8.1-140.8). Furthermore, baseline WMH grade (OR 1.2; 1.1-1.3), lacunar infarcts (OR 2.8; 1.3-6.0), and APOE epsilon2 carriership (OR 4.2; 1.4-12.5) predicted MB incidence. Incident MB patients had more progression of WMH (p < 0.01) and incident lacunar infarcts (p < 0.05). These relations were most prominent for incident nonlobar MBs. Incident strictly lobar MBs were associated with smoking. In addition to APOE genotype, presence and progression of small-vessel disease and vascular risk factors were predictors of new MBs. The latter are potentially modifiable, suggesting the possibility of preventing incident MBs, hopefully resulting in slower clinical decline.
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6.98Impact points
Reduced resting-state brain activity in the "default network" in normal aging.
Cerebral cortex (New York, N.Y. : 1991). 09/2008; 18(8):1856-64.
Normal aging is associated with cognitive decline. Functions such as attention, information processing, and working memory are compromised. It has been hypothesized that not only regional changes, but also alterations in the integration of regional brain activity (functional brain connectivity) unde... [more] Normal aging is associated with cognitive decline. Functions such as attention, information processing, and working memory are compromised. It has been hypothesized that not only regional changes, but also alterations in the integration of regional brain activity (functional brain connectivity) underlie the observed age-related deficits. Here, we examined the functional properties of brain networks based on spontaneous fluctuations within brain systems using functional magnetic resonance imaging. We hypothesized that functional connectivity of intrinsic brain activity in the "default-mode" network (DMN) is affected by normal aging and that this relates to cognitive function. Ten younger and 22 older subjects were scanned at "rest," that is, lying awake with eyes closed. Our results show decreased activity in older versus younger subjects in 2 resting-state networks (RSNs) resembling the previously described DMN, containing the superior and middle frontal gyrus, posterior cingulate, middle temporal gyrus, and the superior parietal region. These results remain significant after correction for RSN-specific gray matter volume. The relevance of these findings is illustrated by the correlation between reduced activity of one of these RSNs and less effective executive functioning/processing speed in the older group.
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2.90Impact points
The renin-angiotensin-aldosterone system in cerebral small vessel disease.
Journal of neurology. 06/2008;
INTRODUCTION : Cerebral small vessel disease (SVD) appears on magnetic resonance imaging (MRI) as leukoaraiosis (LA), état criblé (EC), and multiple lacunar infarctions (MLI). Although the pathophysiology of SVD is poorly understood, there is evidence of a genetic contribution. We sought to analyze ... [more] INTRODUCTION : Cerebral small vessel disease (SVD) appears on magnetic resonance imaging (MRI) as leukoaraiosis (LA), état criblé (EC), and multiple lacunar infarctions (MLI). Although the pathophysiology of SVD is poorly understood, there is evidence of a genetic contribution. We sought to analyze the influence of the reninangiotensin- aldosterone system (RAAS) on SVD in symptomatic patients from the Génétique de l'Infarctus Cérébral (GENIC) study, including RAAS polymorphisms and circulating angiotensin converting enzyme (ACE). METHODS : Caucasian patients (n = 510) with acute brain infarction (BI) were recruited and MRIs were evaluated for SVD, including LA, EC, and MLI. We considered ACE levels and several polymorphisms, including ACE, angiotensinogen, aldosterone synthase CYP11B2, and angiotensin II receptor type I. RESULTS : Among the polymorphisms, there were marginal negative associations between aldosterone synthase CYP11B2 -344C against severe EC (adjusted OR, 0.57; 95 % CI, 0.31- 1.05) and severe LA (adjusted OR, 0.54; 95 % CI, 0.30-0.95), both considering -344C dominant. In addition, the frequency of -344C decreased with the number of SVD abnormalities (p = 0.016). Mean plasma ACE was elevated in patients with MLI, but not with LA or EC. The risk of MLI increased gradually with increasing plasma ACE (adjusted OR, 1.25; 95 % CI, 1.02-1.53). CONCLUSIONS : This exploratory study found no strong evidence for RAAS involvement in severe SVD in this population. The whole spectrum of SVD, including EC, MLI, and LA, can be considered as phenotypes for genetic studies.
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3.12Impact points
Global dynamical analysis of the EEG in Alzheimer's disease: frequency-specific changes of functional interactions.
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology. 05/2008; 119(4):837-41.
OBJECTIVE: EEG coherence is decreased in Alzheimer's disease (AD), suggesting decreased interaction between brain areas. Nonlinear EEG analysis in AD points to decreased complexity of brain dynamics, implicating increased interaction. To clarify these apparently paradoxical findings from linear ... [more] OBJECTIVE: EEG coherence is decreased in Alzheimer's disease (AD), suggesting decreased interaction between brain areas. Nonlinear EEG analysis in AD points to decreased complexity of brain dynamics, implicating increased interaction. To clarify these apparently paradoxical findings from linear and nonlinear analysis, we calculated global coherence and global correlation dimension (D2), a nonlinear measure, in the EEG of patients with probable AD and controls. Our hypothesis is that these measures are related to each other when calculated in a comparable way. METHODS: From 15 patients with probable AD (mean age 63.1 years; SD 6.3) and 21 age-matched controls with subjective memory complaints (mean age 62.8; SD 12.0), band filtered EEG data were analysed in six frequency bands. For each frequency band average coherence and multichannel D2 were determined. RESULTS: ANOVA for repeated measures showed for D2 an interaction between band and group, but not for coherence. In the beta band and upper alpha band, D2 was higher in patients with probable AD compared to controls, while global coherence tended to be lower in these frequency bands in patients with probable AD. In the frequency range from theta to beta, coherence and D2 were inversely correlated without group differences. CONCLUSIONS: When calculated in comparable ways, global correlation dimension and coherence are related measures. In AD, these measures change especially in the higher frequency ranges, both pointing to decreased functional cortical connectivity. SIGNIFICANCE: Both global coherence and global correlation dimension seem to measure global connectivity, but nonlinear measures may be more sensitive. In AD, connectivity measures are not equally impaired in all frequency ranges, possibly reflecting differentiated affection of the dynamical processes responsible for the different frequency bands.
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[Atypical pain in the mandible caused by trigeminal neuralgia]
Nederlands tijdschrift voor tandheelkunde. 02/2008; 115(1):41-3.
A 58-year-old woman came to her dentist with atypical pain on the right side of the mandible. The pain diminished with the use of carbamazepine, paracetamol and diclofenac, and eventually disappeared completely. Magnetic resonance imaging, undertaken at the advice of a neurologist, showed no structu... [more] A 58-year-old woman came to her dentist with atypical pain on the right side of the mandible. The pain diminished with the use of carbamazepine, paracetamol and diclofenac, and eventually disappeared completely. Magnetic resonance imaging, undertaken at the advice of a neurologist, showed no structural lesions and confirmed the diagnosis of idiopathic trigeminal neuralgia. Trigeminal neuralgia is a condition which often can be diagnosed on the basis of the clinical history and the specific symptoms. The condition can be divided into idiopathic and symptomatic trigeminal neuralgia. It is important to consider a possible trigeminal neuralgia in case of atypical pain in the oral region in order to prevent unnecessary dental procedures.
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5.94Impact points
CSF biomarkers and medial temporal lobe atrophy predict dementia in mild cognitive impairment.
Neurobiology of aging. 08/2007; 28(7):1070-4.
OBJECTIVE: To study CSF biomarkers, beta-amyloid(1-42) (Abeta(1-42)) and tau, and medial temporal lobe atrophy (MTA) on MRI in their ability to predict dementia in patients with mild cognitive impairment (MCI). METHODS: Fifty-nine MCI patients (49% male, mean age 69+/-8), follow-up 19 months, were i... [more] OBJECTIVE: To study CSF biomarkers, beta-amyloid(1-42) (Abeta(1-42)) and tau, and medial temporal lobe atrophy (MTA) on MRI in their ability to predict dementia in patients with mild cognitive impairment (MCI). METHODS: Fifty-nine MCI patients (49% male, mean age 69+/-8), follow-up 19 months, were included. Baseline CSF levels of Abeta(1-42), tau and MTA-score were dichotomized. RESULTS: Thirty-three (56%) of the MCI patients progressed to dementia, 30 of which had Alzheimer's disease. Lower CSF Abeta(1-42) level, higher CSF-tau and higher MTA-scores at baseline were found in progressed patients. Cox proportional hazards models revealed that abnormal CSF Abeta(1-42), CSF tau and MTA were significantly associated with dementia at follow-up (hazard ratio (95% confidence interval): 4.0 (1.3-12.1), 5.9 (1.6-21.7) and 2.1 (1.0-4.6)). A fourfold higher risk was found for patients with both abnormal CSF biomarkers and MTA compared to patients with either test abnormal. Ninety-four percent of patients with both abnormalities converted to dementia. CONCLUSIONS: These findings suggest an added value of CSF to MRI in the diagnostic work up of patients presenting at a memory clinic.
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6.98Impact points
Small-world networks and functional connectivity in Alzheimer's disease.
Cerebral cortex (New York, N.Y. : 1991). 02/2007; 17(1):92-9.
We investigated whether functional brain networks are abnormally organized in Alzheimer's disease (AD). To this end, graph theoretical analysis was applied to matrices of functional connectivity of beta band-filtered electroencephalography (EEG) channels, in 15 Alzheimer patients and 13 control ... [more] We investigated whether functional brain networks are abnormally organized in Alzheimer's disease (AD). To this end, graph theoretical analysis was applied to matrices of functional connectivity of beta band-filtered electroencephalography (EEG) channels, in 15 Alzheimer patients and 13 control subjects. Correlations between all pairwise combinations of EEG channels were determined with the synchronization likelihood. The resulting synchronization matrices were converted to graphs by applying a threshold, and cluster coefficients and path lengths were computed as a function of threshold or as a function of degree K. For a wide range of thresholds, the characteristic path length L was significantly longer in the Alzheimer patients, whereas the cluster coefficient C showed no significant changes. This pattern was still present when L and C were computed as a function of K. A longer path length with a relatively preserved cluster coefficient suggests a loss of complexity and a less optimal organization. The present study provides further support for the presence of "small-world" features in functional brain networks and demonstrates that AD is characterized by a loss of small-world network characteristics. Graph theoretical analysis may be a useful approach to study the complexity of patterns of interrelations between EEG channels.
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6.72Impact points
Brain aging in very old men with type 2 diabetes: the Honolulu-Asia Aging Study.
Diabetes care. 11/2006; 29(10):2268-74.
OBJECTIVE: Type 2 diabetes leads to cognitive impairment and dementia, which may reflect microvascular and macrovascular complications as well as neurodegenerative processes. There are few studies on the anatomical basis for loss of cognitive function in type 2 diabetes. The objective of this study ... [more] OBJECTIVE: Type 2 diabetes leads to cognitive impairment and dementia, which may reflect microvascular and macrovascular complications as well as neurodegenerative processes. There are few studies on the anatomical basis for loss of cognitive function in type 2 diabetes. The objective of this study was to investigate the association between type 2 diabetes and markers of brain aging on magnetic resonance images, including infarcts, lacunes, and white matter hyperintensities as markers of vascular damage and general and hippocampal atrophy as markers of neurodegeneration in Japanese-American men born between 1900 and 1919 and followed since 1965 in the Honolulu-Asia Aging Study. RESEARCH DESIGN AND METHODS: Prevalent and incident dementia was assessed. Associations between magnetic resonance imaging markers and diabetic status were estimated with logistic regression, controlling for sociodemographic and other vascular factors. RESULTS: The prevalence of type 2 diabetes in the cohort is 38%. Subjects with type 2 diabetes had a moderately elevated risk for lacunes (odds ratio [OR] 1.6 [95% CI 1.0-2.6]) and hippocampal atrophy (1.7 [0.9-2.9]). The risk for both hippocampal atrophy and lacunes/infarcts was twice as high in subjects with compared with those without type 2 diabetes. Among the group with type 2 diabetes, those with the longest duration of diabetes, those taking insulin, and those with complications had relatively more pathologic brain changes. CONCLUSIONS: There is evidence that older individuals with type 2 diabetes have an elevated risk for vascular brain damage and neurodegenerative changes. These pathological changes may be the anatomical basis for an increased risk of cognitive impairment or dementia in type 2 diabetes.
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2.90Impact points
Simple versus complex assessment of white matter hyperintensities in relation to physical performance and cognition: the LADIS study.
Journal of neurology. 10/2006; 253(9):1189-96.
BACKGROUND: White matter hyperintensities (WMH) on MRI are associated with disorders of gait and balance and with cognitive impairment. The most suitable method to assess WMH in relation to the clinical evaluation of disturbances in these areas has not yet been established. AIM: To compare a simple ... [more] BACKGROUND: White matter hyperintensities (WMH) on MRI are associated with disorders of gait and balance and with cognitive impairment. The most suitable method to assess WMH in relation to the clinical evaluation of disturbances in these areas has not yet been established. AIM: To compare a simple visual rating scale, a detailed visual rating scale and volumetric assessment of WMH with respect to their associations with clinical measures of physical performance and cognition. METHODS: Data were drawn from the multicentre, multinational LADIS study. Data of 574 subjects were available. MRI analysis included assessment of WMH using the simple Fazekas scale, the more complex Scheltens scale and a semi-automated volumetric method. Disturbances of gait and balance and general cognitive function were assessed using the Short Physical Performance Battery (SPPB) and the Mini Mental State Examination (MMSE), respectively. RESULTS: Irrespective of the method of measuring WMH, subjects with disturbances of gait and balance (SPPB < or = 10) had more WMH than subjects with normal physical performance. Subjects with mild cognitive deficits (MMSE < or = 25) had more WMH than subjects with normal cognition. Correlations between clinical measures and WMH were equal across methods of WMH measurement (SPPB: Spearman r = -0.22, -0.25, -0.26, all p < 0.001; MMSE: Spearman r = -0.11, -0.10, -0.09, all p < 0.05, for Fazekas scale, Scheltens scale and volumetry, respectively). These associations remained significant and comparable after correcting for age, gender and education in multivariate linear regression analyses. CONCLUSION: Simple and complex measures of WMH yield comparable associations with measures of physical performance and cognition. This suggests that a simple visual rating scale may be sufficient, when analyzing relationships between clinical parameters and WMH in a clinical setting.
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4.87Impact points
Mild cognitive impairment (MCI) in medical practice: a critical review of the concept and new diagnostic procedure. Report of the MCI Working Group of the European Consortium on Alzheimer's Disease.
Journal of neurology, neurosurgery, and psychiatry. 07/2006; 77(6):714-8.
Mild cognitive impairment (MCI) was proposed as a nosological entity referring to elderly people with mild cognitive deficit but no dementia. MCI is a heterogeneous clinical entity with multiple sources of heterogeneity. The concept of MCI was reviewed and a diagnostic procedure with three different... [more] Mild cognitive impairment (MCI) was proposed as a nosological entity referring to elderly people with mild cognitive deficit but no dementia. MCI is a heterogeneous clinical entity with multiple sources of heterogeneity. The concept of MCI was reviewed and a diagnostic procedure with three different stages was proposed by the European Consortium on Alzheimer's Disease Working Group on MCI. Firstly, MCI should correspond to cognitive complaints coming from the patients or their families; the reporting of a relative decline in cognitive functioning during the past year by a patient or informant; cognitive disorders as evidenced by clinical evaluation; absence of major repercussions on daily life; and absence of dementia. These criteria, similar to those defined during an international workshop in Stockholm, make it possible to identify an MCI syndrome, which is the first stage of the diagnostic procedure. Secondly, subtypes of MCI had to be recognised. Finally, the aetiopathogenic subtype could be identified. Identifying patients at a high risk for progression to dementia and establishing more specific and adapted therapeutic strategies at an early stage, together with more structured overall management, is made possible by the diagnostic procedure proposed.
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4.35Impact points
Corpus callosum size correlates with asymmetric performance on a dichotic listening task in healthy aging but not in Alzheimer's disease.
Neuropsychologia. 02/2006; 44(2):208-17.
Alzheimer's disease (AD) involves not only gray matter but also white matter pathology, as reflected by atrophy of the corpus callosum (CC). Since decreased CC size may indicate reduced functional interhemispheric connectivity, differences in callosal size may have cognitive consequences that ma... [more] Alzheimer's disease (AD) involves not only gray matter but also white matter pathology, as reflected by atrophy of the corpus callosum (CC). Since decreased CC size may indicate reduced functional interhemispheric connectivity, differences in callosal size may have cognitive consequences that may become specifically apparent in neuropsychological tasks that tap hemispheric laterality. In the present study, we examined callosal functioning with a dichotic listening task in 25 Alzheimer patients, 20 healthy elderly and 20 healthy elderly with subjective memory complaints. We found decreased performance, increased ear asymmetry, and decreased callosal size in the AD group compared to healthy elderly. As expected, in the healthy elderly, we found significant negative correlations between ear asymmetry and callosal size, specifically in the anterior and posterior callosal subareas. While the association with the posterior subareas (isthmus and splenium) points at involvement of temporal areas mediating language processing, the association with the anterior subarea (the rostrum and genu) points at involvement of frontal areas mediating attention and executive functions. Remarkably however, in contrast to the healthy elderly, callosal size was not related to ear asymmetry in the AD group. The absence of an association between callosal atrophy and ear asymmetry implies that other pathological processes, next to reduced callosal functioning, attribute to ear asymmetry in AD. Difficulties to attend specifically to the left ear during dichotic listening in some of the AD patients, points at decreased attention and executive functions and suggests that pathology of specifically the frontal areas is involved.
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[Cognitive disorders appearing before the age of 65 in patients of the Alzheimer Centre of the VU Medical Centre: diagnoses and clinical characteristics]
Nederlands tijdschrift voor geneeskunde. 01/2006; 149(51):2862-7.
OBJECTIVE: To obtain a profile of the causes and clinical characteristics of cognitive disorders in patients referred to a memory clinic before the age of 65 years. DESIGN: Retrospective case-note study. METHOD: Data were collected from 127 subjects with objective cognitive disorders who visited the... [more] OBJECTIVE: To obtain a profile of the causes and clinical characteristics of cognitive disorders in patients referred to a memory clinic before the age of 65 years. DESIGN: Retrospective case-note study. METHOD: Data were collected from 127 subjects with objective cognitive disorders who visited the Alzheimer Centre of the VU Medical Centre in Amsterdam, the Netherlands, in the period from 1 January 2001 to 31 December 2003 with an onset of complaints before the age of 65. Besides the diagnoses, we investigated the clinical presentations, the occurrence of cardiovascular risk factors, the family history, and the presence of noncognitive neurological signs. RESULTS: The most common causes of cognitive decline under the age of 65 were Alzheimer's disease (46%) and frontotemporal dementia (23%). Vascular dementia was seen in 5% and dementia with Lewy bodies in 2%; 9% had mild cognitive impairment but no dementia. Hypertension and a positive family history for dementia were each present in 40% of the patients. Non-cognitive neurological abnormalities were found only in cases of non-Alzheimer dementia. During the period under investigation, the number of patients with objective cognitive disorders increased more than did the number without a cognitive disorder. CONCLUSION: Within the population of a memory clinic, Alzheimer's disease was the most frequent cause of cognitive decline under the age of 65, followed by frontotemporal dementia. The distribution differed from causes of dementia at an older age, where vascular dementia had the second place.
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[Alzheimer's disease and treatment of vascular risk factors]
Nederlands tijdschrift voor geneeskunde. 01/2006; 149(51):2844-9.
There is increasing evidence that vascular risk factors including hypertension, high cholesterol, hyperhomocysteinaemia and diabetes mellitus are connected to the risk of Alzheimer's disease (AD). The risk of AD may be reduced by the treatment of hypertension prior to onset of cognitive impairme... [more] There is increasing evidence that vascular risk factors including hypertension, high cholesterol, hyperhomocysteinaemia and diabetes mellitus are connected to the risk of Alzheimer's disease (AD). The risk of AD may be reduced by the treatment of hypertension prior to onset of cognitive impairment. One small randomised clinical trial has provided some evidence of beneficial effects on cognition of cholesterol-lowering drugs such as the statins in patients with AD. Treatment of hypertension, hyperhomocysteinaemia and diabetes mellitus with the aim of halting the progression of cognitive decline in AD is still under study and results are awaited. For the time being findings from the trials carried out thus far should be interpreted with care due to methodological shortcomings, both in study design and execution. In order to investigate the role of vascular risk factors both in the aetiology and treatment of AD, large prospective randomised trials with long-term follow-up of AD patients who have been diagnosed using revised uniform diagnostic criteria that take the heterogeneity of the disease into account, are necessary.
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3.28Impact points
Brain atrophy and lesion load as explaining parameters for cognitive impairment in multiple sclerosis.
Multiple sclerosis (Houndmills, Basingstoke, England). 11/2005; 11(5):524-31.
Multiple sclerosis (MS) is a multifocal demyelinating disease of the central nervous system, with lesions widespread through the brain and spinal cord. An important manifestation is cognitive impairment, which, though difficult to measure, may have a major social impact. To better understand the rel... [more] Multiple sclerosis (MS) is a multifocal demyelinating disease of the central nervous system, with lesions widespread through the brain and spinal cord. An important manifestation is cognitive impairment, which, though difficult to measure, may have a major social impact. To better understand the relationship between structural tissue damage and cognitive impairment, we examined the extent and spatial distribution of brain lesions, as measured by magnetic resonance imaging (MRI), in relation to abnormal cognitive performance as measured by the Brief Repeatable Battery (BRB) in 82 MS patients. Possible confounders, like fatigue, pain and depression were also assessed. Brain MR image analysis included hyperintense T2 and hypointense T1 lesion load in the whole brain and the four lobes separately, as well as whole brain volume measurements. Cognitive impairment (defined as more than two abnormal tests) was found in 67% of the patients. Moderately strong correlations were found between the subtests of the BRB and the lesion loads in the brain regions hypothesized to be associated with that cognitive test, although these correlations were in general not much stronger than those between the subtests and the overall lesion load (due to strong interrelationships). The Spatial Recall Test correlated best with parietal lesion load; the Symbol Digit Modalities Test, the Paced Auditory Serial Addition Task (PASAT) and the Word List Generation best with frontal, parietal and temporal lesion load; while the Verbal List Generation Test Index correlated only with atrophy. Atrophy and lesion load were the main factors determining the test scores, explaining 10-25% of the variance in the test results, and were more important than fatigue, pain and depression; only depression had a minor, but significant, additional effect on the PASAT. In conclusion, cognitive impairment in MS is moderately dependent on amount (and distribution) of structural brain damage, especially in the more physically impaired patients group.
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3.12Impact points
Disturbed fluctuations of resting state EEG synchronization in Alzheimer's disease.
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology. 04/2005; 116(3):708-15.
OBJECTIVE: We examined the hypothesis that cognitive dysfunction in Alzheimer's disease is associated with abnormal spontaneous fluctuations of EEG synchronization levels during an eyes-closed resting state. METHODS: EEGs were recorded during an eyes-closed resting state in Alzheimer patients (N... [more] OBJECTIVE: We examined the hypothesis that cognitive dysfunction in Alzheimer's disease is associated with abnormal spontaneous fluctuations of EEG synchronization levels during an eyes-closed resting state. METHODS: EEGs were recorded during an eyes-closed resting state in Alzheimer patients (N=24; 9 males; mean age 76.3 years; SD 7.8; range 59-86) and non-demented subjects with subjective memory complaints (N=19; 9 males; mean age 76.1 years; SD 6.7; range: 67-89). The mean level of synchronization was determined in different frequency bands with the synchronization likelihood and fluctuations of the synchronization level were analysed with detrended fluctuation analysis (DFA). RESULTS: The mean level of EEG synchronization was lower in Alzheimer patients in the upper alpha (10-13Hz) and beta (13-30Hz) band. Spontaneous fluctuations of synchronization were diminished in Alzheimer patients in the lower alpha (8-10Hz) and beta bands. In patients as well as controls the synchronization fluctuations showed a scale-free pattern. CONCLUSIONS: Alzheimer's disease is characterized both by a lower mean level of functional connectivity as well as by diminished fluctuations in the level of synchronization. The dynamics of these fluctuations in patients and controls was scale-free which might point to self-organized criticality of neural networks in the brain. SIGNIFICANCE: Impaired functional connectivity can manifest itself not only in decreased levels of synchronization but also in disturbed fluctuations of synchronization levels.
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5.74Impact points
Raloxifene exposure enhances brain activation during memory performance in healthy elderly males; its possible relevance to behavior.
NeuroImage. 04/2005; 25(1):63-75.
Raloxifene is a selective estrogen receptor modulator (SERM) that is prescribed in females only, but its use in male subjects is increasingly considered. With a growing number of patients having potential benefit from raloxifene, the need for an assessment of its effects on brain function is growing... [more] Raloxifene is a selective estrogen receptor modulator (SERM) that is prescribed in females only, but its use in male subjects is increasingly considered. With a growing number of patients having potential benefit from raloxifene, the need for an assessment of its effects on brain function is growing. Effects of estrogens on brain function are very subtle and difficult to detect by neuropsychological assessment. Functional imaging techniques, however, have been relatively successful in detecting such changes. This study used functional magnetic resonance imaging (fMRI) to examine effects of raloxifene treatment on memory function. Healthy elderly males (n = 28; mean age 63.6 years, SD 2.4) were scanned during performance on a face encoding paradigm. Scans were made at baseline and after 3 months of treatment with either raloxifene (n = 14) or placebo (n = 14). Treatment effects were analyzed using mixed-effects statistical analysis (FSL). Activation during task performance involved bilateral parietal and prefrontal areas, anterior cingulate gyrus, and inferior prefrontal, occipital, and mediotemporal areas bilaterally. When compared to placebo, raloxifene treatment significantly enhanced activation in these structures (Z > 3.1), except for mediotemporal areas. Task performance accuracy diminished in the placebo group (P = 0.02), but remained constant in the raloxifene group (P = 0.60). In conclusion, raloxifene treatment enhanced brain activation in areas spanning a number of different cognitive domains, suggesting an effect on cortical arousal. Such effects may translate into small effects on behavior, including effects on attention and working memory performance, executive functions, verbal skills, and episodic memory. Further neuropsychological assessment is necessary to test the validity of these predictions.
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0.97Impact points
Biomarker profiles and their relation to clinical variables in mild cognitive impairment.
Neurocase : case studies in neuropsychology, neuropsychiatry, and behavioural neurology. 03/2005; 11(1):8-13.
The aim of the study was to compare clinical variables between MCI patients at different risk for Alzheimer's disease (AD) according to their biomarker profile. Fifty-four percent out of 39 MCI patients had a low Abeta42 and high tau in cerebrospinal fluid (CSF) (high-risk), 26% either a low CSF... [more] The aim of the study was to compare clinical variables between MCI patients at different risk for Alzheimer's disease (AD) according to their biomarker profile. Fifty-four percent out of 39 MCI patients had a low Abeta42 and high tau in cerebrospinal fluid (CSF) (high-risk), 26% either a low CSF Abeta32 or high CSF tau (intermediate-risk) and 20% a normal CSF Abeta42 and tau (low-risk). Both high-and intermediate-risk subjects differed from the low-risk group in episodic memory, executive functions and the preclinical AD scale (PAS),which combines a set of clinical parameters. Subjects at high risk did not differ from subjects with an intermediate risk. Abeta42 levels correlated with the MTA and PAS scores, tau levels with episodic memory. These correlations suggest that the biomarkers are not independent when compared to the other AD markers. Longitudinal studies are necessary to interpret the correlations between biomarkers, imaging, and neuropsychological markers.
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2.32Impact points
MRI and CT in the diagnosis of vascular dementia.
Journal of the neurological sciences. 11/2004; 226(1-2):9-12.
Neuroimaging is necessary to demonstrate cerebrovascular disease (CVD) and is therefore an important examination in vascular dementia (VaD) and vascular cognitive impairment (VCI). MRI is preferred over CT because multiple planes and sequences are needed to assess various types of pathology in relev... [more] Neuroimaging is necessary to demonstrate cerebrovascular disease (CVD) and is therefore an important examination in vascular dementia (VaD) and vascular cognitive impairment (VCI). MRI is preferred over CT because multiple planes and sequences are needed to assess various types of pathology in relevant regions. These protocols allow differentiation of VaD from other forms of dementia and sometimes identify specific underlying disorders. Different diagnostic criteria for VaD exist but the NINDS-AIREN criteria are widely used in controlled clinical trials in VaD. These criteria have relatively low sensitivity but are highly specific and include radiological requirements. The radiological criteria have poor interobserver agreement. In general, the radiological portion of the diagnostic criteria for VaD needs revision and refinement to include bone fide cases of VaD not currently accepted by imaging rules, and for the early detection of patients with VCI.
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4.87Impact points
Intravenous immunoglobulins: a treatment for Alzheimer's disease?
Journal of neurology, neurosurgery, and psychiatry. 11/2004; 75(10):1374-5.
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8.17Impact points
White matter lesion progression: a surrogate endpoint for trials in cerebral small-vessel disease.
Neurology. 08/2004; 63(1):139-44.
There is neuropathologic evidence that confluent MRI white matter lesions in the elderly reflect ischemic brain damage due to microangiopathy. The authors hypothesize that measuring changes in the progression of white matter lesions as shown by MRI may provide a surrogate marker in clinical trials o... [more] There is neuropathologic evidence that confluent MRI white matter lesions in the elderly reflect ischemic brain damage due to microangiopathy. The authors hypothesize that measuring changes in the progression of white matter lesions as shown by MRI may provide a surrogate marker in clinical trials on cerebral small-vessel disease in which the currently used primary outcomes are cognitive impairment and dementia. This hypothesis is based on evidence that confluent white matter lesions progress rapidly as shown in a recent follow-up study in community-dwelling subjects. The mean increase in lesion volume was 5.2 cm(3) after 3 years. Based on these data in a clinical trial, 195 subjects with confluent lesions would be required per treatment arm to demonstrate a 20% reduction in the rate of disease progression over a 3-year period. Like any other MRI metric, the change in white matter lesion volume cannot be considered preferable to clinical outcomes unless it has been demonstrated that it matters to the patient in terms of function.
Following (6)
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Henry C Weinstein
VU medisch centrum -
Henk W Berendse
VU medisch centrum -
Jan Coen Netelenbos
VU medisch centrum -
Guido Nolte
Fraunhofer -
Hugo Vrenken
VU medisch centrum
Topics (5)
