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H Hampel

Publications and source records attributed to H Hampel.

At least 19 recordsLinked to original sources
PubMed2006

Functional connectivity of the fusiform gyrus during a face-matching task in subjects with mild cognitive impairment.

Cognitive function requires a high level of functional interaction between regions of a network supporting cognition. Assuming that brain activation changes denote an advanced state of disease progression, changes in functional connectivity may precede changes in brain activation. The objective of this study was to investigate changes in functional connectivity of the right middle fusiform gyrus (FG) in subjects with mild cognitive impairment (MCI) during performance of a face-matching task. The right middle FG is a key area for processing face stimuli. Brain activity was measured using functional MRI. There were 16 MCI subjects and 19 age-matched healthy controls. The linear correlation coefficient was utilized as a measure of functional connectivity between the right middle FG and all other voxels in the brain. There were no statistical differences found in task performance or activation between groups. The right middle FG of the healthy control and MCI groups showed strong bilateral positive linear correlation with the visual cortex, inferior and superior parietal lobules, dorsolateral prefrontal cortex (DLPFC) and anterior cingulate. The healthy controls showed higher positive linear correlation of the right middle FG to the visual cortex, parietal lobes and right DLPFC than the MCI group, whereas the latter had higher positive linear correlation in the left cuneus. In the healthy controls, the right middle FG had negative linear correlation with right medial frontal gyrus and superior temporal gyrus and with left inferior parietal lobule (IPL), angular gyrus, superior frontal gyrus and anterior cingulate gyrus, but the MCI group had negative linear correlation with the left IPL, angular gyrus, precuneus, anterior cingulate, and to right middle temporal gyrus and posterior cingulate gyrus. In the negatively linearly correlated regions, the MCI group had reduced functional connectivity to the frontal areas, right superior temporal gyrus and left IPL. Different regions of the cuneus and IPL had increased functional connectivity in either group. The putative presence of Alzheimer's disease neuropathology in MCI affects functional connectivity from the right middle FG to the visual areas and medial frontal areas. In addition, higher linear correlation in the MCI group in the parietal lobe may indicate the initial appearance of compensatory processes. The results demonstrate that functional connectivity can be an effective marker for the detection of changes in brain function in MCI subjects.

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PubMed2006

[Reliability of multicenter magnetic resonance imaging. Results of a phantom test and in vivo measurements by the German Dementia Competence Network].

BACKGROUND: Whereas a large body of evidence suggests the usefulness of volumetric measurement of cerebral atrophy for diagnosing Alzheimer's disease (AD), the clinical applicability of cerebral volumetry for early detection of AD across multiple clinical sites is not well known. In the current study, we assessed the precision of volumetric measurement of the brain based on magnetic resonance imaging (MRI) in a multicenter setting. METHODS: The reliability of MRI was assessed by a phantom test of the American College of Radiology and voxel-based morphometry applied to the images obtained from a single subject tested at 11 centers of the German Dementia Competence Network. RESULT: Nine of the 11 centers tested met the reliability criteria of the phantom test. Across all centers, a bias was found in the measurements of slice thickness and length. For voxel-based morphometry, the coefficient of variation yielded 5.02% for gray matter volume and 12.81% (SD 9.06%) for gray matter signal intensity in voxels. Power analysis showed that a sample size of 150 subjects is sufficient for statistically valid detection of reduced gray matter volume in patients with mild cognitive impairment. CONCLUSION: The reliability of measurements from multiple centers is sufficient to allow statistically valid analysis of MRI data.

Adult↗
PubMed2006

[Presenile dementia in memory clinics--incidence rates and clinical features].

This study describes the clinical features of presenile dementia diagnosed in memory clinics. It further gives an estimate of the declared incidence for the German city of Munich and surrounding counties. Twelve memory clinics in Switzerland and Germany were considered, among them all of the four in Munich. A total of 267 patients with onset of illness under the age of 65 were included. Only 16 patients (6%) were younger than 50. Men and women were affected about equally often. The most common cause of dementia was Alzheimer's disease (67%), followed by frontotemporal degeneration (13.5%) and vascular (5.6%) dementia. The declared incidence was estimated at 8.3 new cases of dementia per year among 100,000 persons in the 50-64 age range, with an incidence rate of Alzheimer's disease at 6.3/100,000. It can be concluded that memory clinics fulfill an important function in the care of patients with presenile dementia, since they are highly utilized by younger patients in early stages of the illness.

Adult↗
PubMed2006

Resting state glucose utilization and the CERAD cognitive battery in patients with Alzheimer's disease.

The present study examined the cortical functional representation of neuropsychological domains in Alzheimer's disease (AD) using positron emission tomography (PET) and the neuropsychological assessment battery of the Consortium to Establish a Registry of Alzheimer's Disease (CERAD). Thirty patients with clinical probable AD and 10 elderly healthy controls underwent (18)FDG brain PET imaging during a resting state. Correlations between metabolic values and cognitive measures were determined using a region of interest analysis with NEUROSTAT (University of Michigan, USA) and a voxel-based analysis with SPM96 (Wellcome Department, London, UK). Specific correlations were seen between measures of episodic memory, verbal fluency and naming and left hemispheric temporal and prefrontal metabolism. Drawing was correlated with metabolism in left prefrontal and left inferior parietal regions. The presented data support the use of metabolic-cognitive correlations to demonstrate the neuronal substrates of cognitive impairment in AD. Subtests of the CERAD battery give a good representation of left, but not of right hemisphere function in AD.

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PubMed2005

Task difficulty in a simultaneous face matching task modulates activity in face fusiform area.

The level of difficulty of a task can alter the neural network that activates for performance of the task. Previous studies have shown increased activation with task difficulty in the frontal lobes while the effects in the extrastriate visual areas have been unclear. We hypothesized that the face fusiform area (FFA), an area specialized for face processing, would increase activation as task difficulty increased in a face matching task. The difficulty level was increased by degrading the quality of the images. The degradation levels were 10%, 20%, 40% and 60%. Based on the correct response rate, the data were divided into a baseline level (composed of non-degraded and 10% degraded images) and a difficult level (composed of the 20%, 40% and 60% degraded images). Brain activation was measured using functional magnetic resonance imaging. The baseline face matching task activated a wide network of regions that included bilaterally the occipital, temporal and parietal lobes and the right frontal lobe. A novel behavioral finding was that task difficulty did not linearly increase with image degradation. The novel brain imaging finding was that the FFA is modulated by task difficulty and performance in the task was linearly correlated to activation in FFA. In addition, we found that activation in the dorsolateral prefrontal cortex (DLPFC) had increased activation as task difficulty increased. When adding the response time as a covariate, the differences in the DLPFC did not remain statistically significant. Increased task difficulty also led to a decrease in activation of visual areas in the extrastriate cortex. Task difficulty increased activation in the FFA to enhance the face processing and suppressed activation in visual extrastriate areas that processed low level properties of the stimuli. Task difficulty led to enhanced response in the FFA and suppressed response in other visual areas.

Adult↗
PubMed2005

Association between cognitive performance and cortical glucose metabolism in patients with mild Alzheimer's disease.

BACKGROUND: Neuronal and synaptic function in Alzheimer's disease (AD) is measured in vivo by glucose metabolism using positron emission tomography (PET). OBJECTIVE: We hypothesized that neuronal activation as measured by PET is a more sensitive index of neuronal dysfunction than activity during rest. We investigated if the correlations between dementia severity as measured with the Mini Mental State Examination (MMSE) and glucose metabolism are an artifact of brain atrophy. METHOD: Glucose metabolism was measured using [18F]fluorodeoxyglucose PET during rest and activation due to audiovisual stimulation in 13 mild to moderate AD patients (MMSE score > or = 17). PET data were corrected for brain atrophy. RESULTS: In the rest condition, glucose metabolism was correlated with the MMSE score primarily within the posterior cingulate and parietal lobes. For the activation condition, additional correlations were within the primary and association audiovisual areas. Most local maxima remained significant after correcting for brain atrophy. CONCLUSION: PET activity measured during audiovisual stimulation was more sensitive to functional alterations in glucose metabolism in AD patients compared to the resting PET. The association between glucose metabolism and MMSE score was not dependent on brain atrophy.

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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

Longitudinal CSF and MRI biomarkers improve the diagnosis of mild cognitive impairment.

The diagnosis of Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI) is limited because it is based on non-specific behavioral and neuroimaging findings. The lesions of Alzheimer's disease: amyloid beta (Abeta) deposits, tau pathology and cellular oxidative damage, affect the hippocampus in the earlier stages causing memory impairment. In a 2-year longitudinal study of MCI patients and normal controls, we examined the hypothesis that cerebrospinal fluid (CSF) markers for these pathological features improve the diagnostic accuracy over memory and magnetic resonance imaging (MRI)-hippocampal volume evaluations. Relative to control, MCI patients showed decreased memory and hippocampal volumes and elevated CSF levels of hyperphosphorylated tau and isoprostane. These two CSF measures consistently improved the diagnostic accuracy over the memory measures and the isoprostane measure incremented the accuracy of the hippocampal volume achieving overall diagnostic accuracies of about 90%. Among MCI patients, over 2 years, longitudinal hippocampal volume losses were closely associated with increasing hyperphosphorylated tau and decreasing amyloid beta-42 levels. These results demonstrate that CSF biomarkers for AD contribute to the characterization of MCI.

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PubMed2005

[Diagnostics and therapy of depressive symptoms in schizophrenic patients].

The occurrence of depressive symptoms in schizophrenia is fairly common. In contrast to earlier assumptions, they usually have unfavorable consequences on the course of the disease. The response of depressive symptoms to therapy is well documented by empirical evidence and studies. In reality, however, the treatment of depressive symptoms in cases of schizophrenia occurs too rarely. This lack of medical treatment is partially explained by the clinicians' apprehension that antidepressive therapy could provoke a flare up of the psychosis. Nonetheless, this situation is often founded on the incorrect assessment of the depressive symptoms as negative symptoms that, in turn, are regarded by many clinicians as having limited treatability. In regards to this circumstance, a rethinking is desirable and, as a matter of principle, necessary.

Antidepressive Agents↗
PubMed2005

[Modern therapy for dementia].

The most frequently diagnosed dementia diseases include Alzheimer disease (AD), vascular dementia (VD) and dementia with Lewy bodies. Cholinesterase (ChE) inhibitors and the NMDA receptor antagonist memantine are currently recommended as first line drugs for the treatment of AD. These anti-dementia drugs have not yet been approved for the treatment of VD and DLB although the results of controlled clinical studies support the effectiveness of the ChE inhibitors for both diseases. The treatment of the primary disease and the secondary prevention of cerebrovascular accidents constitute the primary objectives of VD therapy. Although single or multiple domain cognitive deficits are the clinical key symptoms of dementia, noncognitive psychopathological symptoms (so-called behavioral disorders) are particularly common and may even dominate the clinical course in the moderate to severe stages. Therefore, it is important to recognize, diagnose and specifically treat these additional symptoms. During the last decade, the classic neuroleptics and benzodiazepine have been largely replaced by modern antidepressants, atypical antipsychotics and benzodiazepine analogues.

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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.

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PubMed2005

EEG coherence reflects regional corpus callosum area in Alzheimer's disease.

OBJECTIVE: Correlations between corpus callosum size and interhemispheric EEG coherence were investigated as measures of interhemispheric connectivity in patients with Alzheimer's disease. METHODS: 11 patients underwent both magnetic resonance imaging and quantitative electroencephalography to assess corpus callosum size and interhemispheric coherence. For comparison, corpus callosum size was measured in 24 healthy elderly control subjects. RESULTS: Corpus callosum cross sectional area was significantly reduced in Alzheimer patients relative to controls. Posterior interhemispheric coherence (alpha and beta frequencies) correlated significantly with the size of posterior corpus callosum area, and anterior coherence (delta, theta, and alpha frequencies) with the size of anterior corpus callosum area in the Alzheimer patients. CONCLUSION: Region specific correlations between corpus callosum size and EEG coherence suggest that the decline in interhemispheric connectivity in Alzheimer's disease results from a specific loss of cortical association neurones projecting through the corpus callosum.

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PubMed2004

MSH6 missense mutations are often associated with no or low cancer susceptibility.

Mismatch repair (MMR) deficiency in tumours from patients with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome is mainly caused by mutations in the MLH1, MSH2, and MSH6 genes. A major challenge in the clinical management of patients with suspected HNPCC is the frequent occurrence of missense mutations in MSH6. These can be considered neither deleterious nor clinically innocent a priori. To assess their significance we studied five novel MSH6 missense mutations in six patients derived from a series of consecutive endometrial and colorectal cancer patients selected for study after their tumours were determined to be microsatellite unstable. We tested each mutated protein for heterodimerisation with MSH2 and for in vitro MMR capability. Four mutations (R128L, P623L, K728T, G881K+S) showed no impairment of these functions while the fifth (E1193K) displayed marked impairment of both functions. These results, taken together with our previous similar findings concerning six other missense mutations in MSH6, allow us to conclude that many or most missense changes in MSH6 likely are clinically innocent, whereas some missense changes such as E1193K, which lead to impaired MMR, are likely to be clinically significant, but have low penetrance.

Base Pair Mismatch↗
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.

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PubMed2004

Value of CSF beta-amyloid1-42 and tau as predictors of Alzheimer's disease in patients with mild cognitive impairment.

Subjects with mild cognitive impairment (MCI) are at a high risk of developing clinical Alzheimer's disease (AD). We asked to what extent the core biomarker candidates cerebro-spinal fluid (CSF) beta-amyloid(1-42) (Abeta(1-42)) and CSF tau protein concentrations predict conversion from MCI to AD. We studied 52 patients with MCI, 93 AD patients, and 10 healthy controls (HC). The MCI group was composed of 29 patients who had converted to AD during follow-up, and of 23 patients who showed no cognitive decline. CSF Abeta(1-42) and tau protein levels were assessed at baseline in all subjects, using enzyme-linked immunosorbent assays. For assessment of sensitivity and specificity, we used independently established reference values for CSF Abeta(1-42) and CSF tau. The levels of CSF tau were increased, whereas levels of Abeta(1-42) were decreased in MCI subjects. Abeta(1-42) predicted AD in converted MCI with a sensitivity of 59% and a specificity of 100% compared to HC. Tau yielded a greater sensitivity of 83% and a specificity of 90%. In a multiple Cox regression analysis within the MCI group, low baseline levels of Abeta(1-42), but not other predictor variables (tau protein, gender, age, apolipoprotein E epsilon4 carrier status, Mini Mental Status Examination score, observation time, antidementia therapy), correlated with conversion status (P<0.05). Our findings support the notion that CSF tau and Abeta(1-42) may be useful biomarkers in the early identification of AD in MCI subjects.

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