Search PubMed⌕ Search

Biomedical subjects

F Müller-Spahn

Publications and source records attributed to F Müller-Spahn.

At least 19 recordsLinked to original sources
PubMed2000

Alzheimer's disease, depression and normal ageing: merit of simple psychomotor and visuospatial tasks.

INTRODUCTION: A brief psychometric test battery was used to differentiate Alzheimer's disease (AD) patients from patients with depression and healthy age-matched control subjects. The purpose was to investigate the discriminative value of simple psychomotor and visuospatial tasks that were implemented in a computer-assisted test battery. METHODS: Manumotoric coordination, discrimination reaction time and performance on a visuospatial pattern-matching task were assessed. Subjects were 30 patients with the diagnosis of probable AD (mild to moderate), 22 patients with a major depression and 15 healthy normal control subjects. RESULTS: Discrimination reaction time separated the three groups most distinctly, but general level of cognitive functioning was a significantly confounding variable. There were no differences between the AD and the depressed patients when the MMSE was used as a covariate. Substantial deficiencies in manumotoric coordination were found in both demented and depressed patients. The visual pattern-matching task yielded longer reaction times in both patient groups than in the control group. CONCLUSION: Translated into neuropsychological terms, these data suggest deficiencies in basic central operations, a slowing of central information processing and attentional deficits in AD and depressed patients. Psychomotor tasks were able to distinguish effectively healthy elderly persons from AD and depressed patients. This test battery, however, appears to be limited in differentiating AD from depression.

Aged↗
PubMed2000

Mercury induces cell cytotoxicity and oxidative stress and increases beta-amyloid secretion and tau phosphorylation in SHSY5Y neuroblastoma cells.

Concentrations of heavy metals, including mercury, have been shown to be altered in the brain and body fluids of Alzheimer's disease (AD) patients. To explore potential pathophysiological mechanisms we used an in vitro model system (SHSY5Y neuroblastoma cells) and investigated the effects of inorganic mercury (HgCl2) on oxidative stress, cell cytotoxicity, beta-amyloid production, and tau phosphorylation. We demonstrated that exposure of cells to 50 microg/L (180 nM) HgCl2 for 30 min induces a 30% reduction in cellular glutathione (GSH) levels (n = 13, p<0.001). Preincubation of cells for 30 min with 1 microM melatonin or premixing melatonin and HgCl2 appeared to protect cells from the mercury-induced GSH loss. Similarly, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assays revealed that 50 microg/L HgCl2 for 24 h produced a 50% inhibition of MTT reduction (n = 9, p<0.001). Again, melatonin preincubation protected cells from the deleterious effects of mercury, resulting in MTT reduction equaling control levels. The release of beta-amyloid peptide (Abeta) 1-40 and 1-42 into cell culture supernatants after exposure to HgCl2 was shown to be different: Abeta 1-40 showed maximal (15.3 ng/ml) release after 4 h, whereas Abeta 1-42 showed maximal (9.3 ng/ml) release after 6 h of exposure to mercury compared with untreated controls (n = 9, p<0.001). Preincubation of cells with melatonin resulted in an attenuation of Abeta 1-40 and Abeta 1-42 release. Tau phosphorylation was significantly increased in the presence of mercury (n = 9, p<0.001), whereas melatonin preincubation reduced the phosphorylation to control values. These results indicate that mercury may play a role in pathophysiological mechanisms of AD.

Amyloid beta-Peptides↗
PubMed1999

[Psychotropic drugs].

With the introduction of the antipsychotic compound Chlorpromazine in the early 1950s began the era of psychotropic drugs. These include a large number of different classes of compounds. They have been clearly demonstrated to be more effective than placebo in the treatment of psychiatric disorders. Anxiolytic and hypnotic drugs are the most commonly prescribed agents. In the past decade many new antidepressants and antipsychotics with a more favorable side-effect profile have been introduced onto the market, and have dramatically widened our possibilities to improve the course of the various psychiatric disorders. The administration of psychotropic drugs is primarily syndrome-related. So far, specific causal therapy is not available.

Antidepressive Agents↗
PubMed1999

ELISA-quantitation of phosphorylated tau protein in the Alzheimer's disease brain.

A reliable, sensitive and specific sandwich ELISA for the quantitation of paired helical filament (PHF) tau in human brain was developed using well-defined monoclonal antibodies. We examined rapid-autopsy-derived brain tissue from 21 neuropathologically confirmed Alzheimer's disease (AD) patients and 14 nondemented controls, matched for age, sex and postmortem delay times. We demonstrated significant elevations of phosphorylated tau levels in the frontal and parietal cortex as well as in the hippocampus of AD patients as compared to the nondemented controls. No difference was observed in the cerebellum. Phosphorylated tau levels measured by ELISA were significantly correlated with the presence or absence of neurofibrillary tangles.

Aged↗
PubMed1998

Decreased trkA neurotrophin receptor expression in the parietal cortex of patients with Alzheimer's disease.

The cholinergic neurons of the basal forebrain system are sensitive to nerve growth factor (NGF), a member of the neurotrophin gene family. Since the cholinergic system is affected early in the course of Alzheimer's disease (AD), it was hypothesized that a deficit in NGF, e.g. reduced neurotrophin uptake by specific receptors, may play a role in neuronal cell death in AD. We quantitated mRNA levels of neurotrophins (NGF, BDNF, NT-3, NT-4/5) and their receptors (trkA, trkB, trkC, p75) in AD postmortem parietal cortex (n = 16) and cerebellum (n = 11). We applied highly sensitive reverse transcription-polymerase chain reaction (RT-PCR) in rapid autopsy derived brain tissue (mean postmortem delay 147+/-96 min., n = 53) to minimize postmortem mRNA variations. In the AD parietal cortex trkA mRNA levels were more than two times lower as compared to controls (n = 16, mean+/-SEM 0.26+/-0.07 units/S12, range, 0-1.78, and n = 11, 0.59+/-0.10 units/S12, range, 0.17-1.10, respectively, P = 0.015). TrkA mRNA levels did not appear to be altered in the AD cerebellum as compared to normal human cerebellum. NGF, BDNF, NT-3, NT-4/5, as well as trkB, trkC and p75 mRNA levels were unchanged in AD parietal cortex and cerebellum as compared to controls. This finding suggests that a reduced expression of the trkA receptor may contribute to impaired NGF-trkA signalling and a reduced transport of NGF in cholinergic neurons. These results reveal a central specific role of the high affinity NGF receptor during neurodegeneration in AD.

Aged↗
PubMed1998

Increased blood mercury levels in patients with Alzheimer's disease.

Alzheimer's disease (AD) is a common neurodegenerative disorder that leads to dementia and death. In addition to several genetic parameters, various environmental factors may influence the risk of getting AD. In order to test whether blood levels of the heavy metal mercury are increased in AD, we measured blood mercury concentrations in AD patients (n = 33), and compared them to age-matched control patients with major depression (MD) (n = 45), as well as to an additional control group of patients with various non-psychiatric disorders (n = 65). Blood mercury levels were more than two-fold higher in AD patients as compared to both control groups (p = 0.0005, and p = 0.0000, respectively). In early onset AD patients (n = 13), blood mercury levels were almost three-fold higher as compared to controls (p = 0.0002, and p = 0.0000, respectively). These increases were unrelated to the patients' dental status. Linear regression analysis of blood mercury concentrations and CSF levels of amyloid beta-peptide (A beta) revealed a significant correlation of these measures in AD patients (n = 15, r = 0.7440, p = 0.0015, Pearson type of correlation). These results demonstrate elevated blood levels of mercury in AD, and they suggest that this increase of mercury levels is associated with high CSF levels of A beta, whereas tau levels were unrelated. Possible explanations of increased blood mercury levels in AD include yet unidentified environmental sources or release from brain tissue with the advance in neuronal death.

Aged↗
PubMed1998

Predictors of relapse and rehospitalization in schizophrenia and schizoaffective disorder.

In a German multicenter treatment study, 354 patients with schizophrenia and schizoaffective disorder were followed for 2 years. The data collected were taken as a basis for the present predictor study. For the first time, the technique of classification and regression tree (CART) analysis has been employed for this purpose. CART yielded informative data and appeared to be a useful instrument in predictor research. On the outcome variables "relapse" and "rehospitalization," significant predictor variables were found in several areas: neuroleptic treatment, onset and previous course (precipitating factors, first manifestation, hospitalization in the preceding year, suicide attempts), psychopathology (residual type, schizoaffective disorder), social adjustment (marital status, employment, intensity of life, Phillips score), previous life experiences (traumatic experiences and psychiatric or developmental disturbances in childhood), and biology (gender, age). Our investigation confirmed the generally prevalent views regarding the value of neuroleptic treatment, the multifactorial etiology, and the vulnerability stress model of schizophrenia.

Adult↗
PubMed1998

Cerebrospinal fluid levels of amyloid precursor protein and amyloid beta-peptide in Alzheimer's disease and major depression - inverse correlation with dementia severity.

Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by progressive dementia that ultimately leads to death. Histopathological hallmarks of AD include brain amyloid deposits and neurofibrillary tangles. Major depression is a frequent diagnosis in every gerontopsychiatric clinic that sees patients with both cognitive and affective disorders. Many depressed patients, in fact, are clinically characterized by cognitive impairments. Thus, an assay that excludes - or confirms - probable AD in cognitively impaired patients is desirable. Such assays may use protein markers that are derived from such histopathologically relevant molecules as the amyloid precursor protein (APP) and its derivatives including the amyloid beta-peptides (Abeta). To evaluate the differential diagnostic properties of cerebrospinal fluid (CSF) Abeta and secreted soluble ectodomain (APPs), we quantitated CSF levels of these measures in AD patients and compared them to age-matched control patients with major depression. CSF levels of APPs and Abeta were similar in patients with AD or major depression, and the apolipoprotein E genotype had no influence on CSF levels of Abeta in AD patients. Measurement of Abeta peptide using a novel zinc/copper capture ELISA that detects aggregated Abeta peptides as well demonstrated similar levels in AD and major depression. In AD patients, CSF levels of total Abeta (Abeta1-40 plus Abeta1-42) were inversely correlated with a functional measure of dementia severity (NOSGER), suggesting that CSF levels of Abeta decrease with advancing severity of AD. Thus, CSF levels of Abeta are not useful for the differentiation of AD from major depression. However, CSF levels of Abeta reflect the severity of dementia and may be useful as biological markers of the stage of the disease.

Aged↗
PubMed1998

Histological markers in nasal mucosa of patients with Alzheimer's disease.

Neuropathological changes such as dystrophic neurites and the presence of abnormal tau protein in the olfactory system, including primary sensory cells and nerve fibres have previously been demonstrated in nasal mucosa tissue of patients with Alzheimer's disease (AD). These changes were detected in autopsy-derived material from histopathologically confirmed AD cases as well as in biopsy tissue from clinical severely ill AD patients. To investigate the potential usefulness for the early diagnosis of AD, we obtained biopsy tissue from olfactory mucosa from 5 clinically mild to moderate AD patients and stained for the presence of tau or beta-amyloid by immunocytochemistry using a panel of specific antibodies. No positive staining was found in any of the cases. For comparison, post-mortem olfactory tissue from AD patients with severe neuropathological changes (widespread neurofibrillary tangles and amyloid in the brain) was investigated. In these severe cases, tau immunoreactivity was found in fine nerve fibres in the lamina propria and in a few olfactory epithelial cells. These results are consistent with other reports showing that cytoskeletal changes and tau pathology in the olfactory epithelium are not primary (or specific) features of AD and may occur predominantly in late stages of the disease.

Aged↗
PubMed1998

[The social status of schizophrenic patients].

In the German multicenter ANI study comparing continuous prophylactic treatment with intermittent medication, the social situation of a large sample of 364 schizophrenic patients was investigated and followed up over a 2-year period of outpatient aftercare. Effective therapy and prophylaxis substantially reduced relapses and rehospitalization. On the other hand, the psychosocial situation still showed considerable disadvantages. Of the patients (35 years old on average), 60% were still unmarried. Almost one-half of the patients still lived alone or with their parents, and one-third lived a very solitary life. At the end of the 2-year aftercare period, one-third was able to earn their own living. Almost one-half retired early from their occupations. Predictors and intervening variables are presented in order to stimulate early rehabilitation approaches. Schizophrenics are particularly placed at a disadvantage by tighter competition in the employment market, even though the course of illness can be improve. Social psychiatry must to be involved in helping to improve social contacts, accommodation and employment in order to prevent major distress.

Adult↗
PubMed1997

Interleukin-6 (IL-6) and soluble forms of IL-6 receptors are not altered in cerebrospinal fluid of Alzheimer's disease patients.

We quantitated interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R) and soluble form of the IL-6 signal-transducing protein gp130 (sgp130) in cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD) (n = 17) and control subjects (n = 18) using sensitive enzyme-linked immunosorbent assays (ELISA). Our results show that none of the parameters examined was significantly different in CSF of AD patients as compared to control age-matched non-demented patients. We conclude that CSF levels of IL-6 and their soluble receptors do not necessarily reflect local changes of the IL-6 system that has been shown to be involved in neurodegenerative events occurring in AD. Levels of sgp130 are substantially high (approximately 100 ng/ml) in the CSF of all individuals probably representing a high antagonistic potential.

Aged↗
PubMed1997

Decrease in parietal cerebral hemoglobin oxygenation during performance of a verbal fluency task in patients with Alzheimer's disease monitored by means of near-infrared spectroscopy (NIRS)--correlation with simultaneous rCBF-PET measurements.

We used near-infrared spectroscopy (NIRS) to study non-invasively changes in cerebral hemoglobin oxygenation in the frontal and parietal cortex during performance of a verbal fluency task in patients with Alzheimer's disease (AD). Whereas healthy elderly subjects (n = 19, age 67 +/- 10 years) showed increases in concentrations of oxygenated hemoglobin [HbO2] (mean (arbitrary units) +/- S.E.M., 1.44 +/- 0.59) and total hemoglobin [HbT] (0.92 +/- 0.81) over the left superior parietal cortex, patients with AD (n = 19, age 71 +/- 10 years) showed significant decreases in [HbO2] (-3.26 +/- 1.30, P < 0.01) as well as [HbT] (-4.45 +/- 1.57, P < 0.01). [HbR] decreased slightly in both groups (-0.62 +/- 0.29 and - 1.18 +/- 0.40, respectively). Using two pairs of NIRS optodes placed on the left superior partietal cortex and on the left prefrontal cortex simultaneous increases in [HbO2] as well as [HbT] in both cortical regions in the healthy elderly subjects (n = 8, age 60 +/- 15) were demonstrated during performance of the task. AD patients (n = 10, age 65 +/- 13 years) showed decreases in [HbO2] and [HbT] in the parietal cortex and, at the same time, increases in [HbO2] and [HbT] in the frontal cortex. Simultaneous NIRS-[HbT] and PET-rCBF measurements showed a significant correlation both when calculated in a 'banana' shaped volume approximated by using cortical thresholds as well as when calculated in a semisphere volume of brain tissue beneath the optodes placed on the head surface (patients with AD, n = 10). The correlation was dependent on the assumed penetration depth of the near-infrared light and was best for all three NIRS variables ([HbO2], [HbR] and [HbT]) when calculated using a semisphere radius of 0.45 cm to 1.35 cm. In conclusion, in Alzheimer's disease a marked reduction of regional cerebral blood flow and cerebral hemoglobin oxygenation may occur during activation of brain function, probably mainly in degenerating brain areas, such as the parietal cortex.

Aged↗
PubMed1997

Dependence of cerebrospinal fluid Tau protein levels on apolipoprotein E4 allele frequency in patients with Alzheimer's disease.

Consistent pathological hallmarks of Alzheimer's disease (AD) are the formation of brain amyloid and neurofibrillary tangles (NFTs). Levels of the major protein component of NFTs, the microtubule associated protein Tau, were shown to be increased in cerebrospinal fluid (CSF) of AD patients as compared to age-matched controls. The presence of apolipoprotein E-epsilon 4 allele (APOE4) is a risk factor for sporadic and familial late-onset AD. ApoE may interact with the binding of Tau to microtubules and Tau phosphorylation in an isoform-specific manner. We investigated whether direct evidence of an isoform-specific interaction of apoE and Tau can be demonstrated in the CSF of live AD patients. We measured the apoE genotype and CSF levels of Tau in 19 patients with probable AD and 12 age-matched control subjects. We found that CSF levels of Tau increase with increasing APOE allele frequency (Spearman rank correlation, zeta = 2.71, P = 0.007). This finding may be in agreement with reports of a lesser binding of apoE4 to Tau, compared to apoE2 and apoE3, resulting in higher levels of unbound Tau in CSF.

Aged↗
PubMed1997

[Central to decentralized admission to the psychiatric hospital. Effects of changed admission circumstances on structure and process quality].

The study provides empirical data to compare different systems used for hospital admission procedures in a psychiatric clinic. The Psychiatric University Clinic Basel replaced its traditional central admission ward by direct admission to a number of different treatment settings. This change had consequences for both structural and procedural quality. More admissions occurred after prior notice had been given, and these admissions occurred more often at a time of day when more clinic staff were available. The rate of voluntary admissions increased, and the continuity of care, as measured by the number of transfers within the clinic during the first 5 days post-admission, was improved. These findings, which support an interpretation that the treatment conditions were improved, must be balanced against the drawback of delayed decision-making processes with, for example, longer waiting times for the patient. However, the continuity of therapeutic relationships can be increased through further changes in the procedural quality.

Adult↗
PubMed1997

[Structural magnetic resonance tomography in diagnosis and research of Alzheimer type dementia].

One of the most widely used neuroimaging procedures in Psychiatry and Neurology is magnetic resonance imaging (MRI). MRI has gained the position of a standard investigation in the differential diagnosis of dementia syndromes. In the clinical diagnosis of Alzheimer's disease (AD) MRI helps to improve the diagnostical accuracy. Recently new MRI-based techniques for performing volumetric measurement of cortical and subcortical structures have been developed. First reports indicate that MRI-based volumetric measurements can be accurate in differentiating AD patients from cognitively normal elderly individuals. These new techniques may be useful adjunct in assessing the clinical diagnosis of AD. Results could also yield insight in the fundamental pathology of the degenerative disease. It is the objective of this chapter to summarize and comment on the significance of MRI in the diagnosis and research of AD. Future directions are outlined, including the use of microscopic MRI, the differentiation of white matter signal hyperintensities and the combined evaluation of structural MRI and functional imaging techniques.

Adult↗