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Biomedical subjects

C Hock

Publications and source records attributed to C Hock.

At least 55 records · Page 3Linked to original sources
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

Assessment of local brain activation. A simultaneous PET and near-infrared spectroscopy study.

In five healthy human subjects, near-infrared spectroscopy (NIRS) and positron emission tomography (PET) examinations were performed simultaneously. Changes in [oxy-Hb], [deoxy-Hb] and [total-Hb] as measured by NIRS over the left forehead were compared to measurements of cerebral blood flow by PET during rest and during performance of a calculation task and a Stroop task. When a penetration depth of near-infrared light 0.9 cm into the brain cortex was assumed, a statistically significant correlation between changes in CBF and changes in [total-Hb] was found. These data confirm the validity of NIRS measurements in human adults.

Aged↗
PubMed1996

Near infrared spectroscopy in the diagnosis of Alzheimer's disease.

Near infrared spectroscopy (NIRS) is a new technique that permits noninvasive monitoring of cerebral blood and tissue oxygenation. Recently, we and others have shown that NIRS measurements are sensitive enough to follow changes in cerebral hemoglobin oxygenation due to activation of brain function. Based on these findings we have assessed the influence of aging as well as the influence of neurodegeneration on cerebral hemoglobin oxygenation during mental work. The typical NIRS pattern in young healthy subjects while performing calculation tasks measured in the frontal cortex were increases in oxygenated hemoglobin [HbO2] and total hemoglobin [HbT] while reduced hemoglobin [HbR] decreased. Elderly healthy subjects showed a significant lower mean increase in [HbO2] and [HbT] levels. Regression analysis revealed an age-dependent decline in activation-induced local increase of [HbO2] as well as [HbT]. Furthermore, we monitored changes in cerebral hemoglobin oxygenation in the frontal cortex while patients with probable Alzheimer's disease (AD) performed cognitive tasks. Whereas elderly healthy subjects (as well as patients with major depression, age-associated memory impairments or vascular dementia) again showed clear increases in the local concentrations of [HbO2] and [HbT] during brain activation, AD patients showed significant decreases compared to the baseline levels in both variables that were most pronounced in the parietal cortex. To clarify whether the different patterns in cerebral hemoglobin oxygenation during cognitive activation were due to an altered functional brain organization in AD or to alterations in the cerebrovascular response to neuronal activation, we are currently performing simultaneous NIRS and (015-H20-)PET measurements during performance of a cognitive task (Stroop test). Our finding of a regional reduced oxygen supply during activation of brain function may be of relevance to the development and the time course of neurodegeneration.

Aging↗
PubMed1996

Computer-based cognitive training in Alzheimer's disease patients.

Memory training programs for cognitively impaired patients have often been criticized for their lack of relevance to everyday activities. We therefore report our experience with four patients suffering from probable Alzheimer's disease, who were trained with a new computer-based program recently developed by our research group. An everyday task of personal relevance to the patient is simulated and trained on a PC-touch-screen using personal photographs of the patient's surroundings and biography. According to the degree of cognitive impairment, training has three major aspects 1) social competence in patients with beginning deficiencies, 2) orientation in patients with moderate disease, and 3) emotional aspects in patients with advanced deficiencies. The patient's training performance improved substantially. While psychopathometric tests showed no significant effects with regard to general cognitive performance, levels of motivation were high and there was a positive acceptance of the training and signs of emotional activation.

Aged↗
PubMed1996

The psychobiology of the acute schizophrenic episode.

Despite intensive worldwide attempts to clarify the pathogenesis of schizophrenia many questions are still open. Evidence is accumulating to suggest that structural abnormalities in various cortical and limbic areas result at least partly from neurodevelopmental disturbances. Prenatal and/or perinatal factors are supposed to play an important role. There is a growing belief that acute schizophrenic symptomatology might be a result of deficits in the sensory filtering process at the level of the thalamus. Several neurotransmitter systems have been implicated in the pathophysiology of schizophrenia, supporting a neurotransmitter imbalance model. Dysfunctions of the dopaminergic and glutamatergic systems may be predominantly involved.

Acute Disease↗
PubMed1995

Age dependency of changes in cerebral hemoglobin oxygenation during brain activation: a near-infrared spectroscopy study.

We used near-infrared spectroscopy (NIRS) to study noninvasively the influence of aging on changes in the local concentration of oxygenated hemoglobin ([HbO2]), reduced hemoglobin ([HbR]), and total hemoglobin ([HbT] = [HbR] + [HbO2]) during activation of brain function. Young subjects (n = 12; age, 28 +/- 4 years) performing calculation tasks showed an increase in [HbO2] [mean (arbitrary units) +/- SD, 2.36 +/- 1.07] and [HbT] (2.24 +/- 1.13) in the frontal cortex, while [HbR] (-0.11 +/- 0.48) decreased. Elderly subjects (n = 17; age, 52 +/- 10 years) showed a significantly lower mean increase (p < 0.05) in [HbO2] and [HbT] levels (1.21 +/- 1.38 and 0.72 +/- 1.41, respectively). Regression analysis supports the hypothesis of an age-dependent decline in the activation-induced local increase in [HbO2] (y = -0.241x + 20.062; r = -0.431, p < 0.05) as well as [HbT] (y = -0.346x + 22.496; r = -0.568, p < 0.05). We conclude that NIRS is a promising approach for studying changes in Hb oxygenation during brain activation in physiological aging.

Adult↗
PubMed1995

Reduced beta-amyloid response in lymphocytes of patients with Alzheimer's disease.

The beta-amyloid peptide (beta A4) is a principal constituent of senile plaques and is thought to play a major role in the pathophysiology of Alzheimer's disease (AD). Although the mechanism of beta-A4 neurotoxicity is still a matter of debate, one of its effects might be a destabilization of cellular calcium homeostasis, thus promoting neuronal damage. The influence of the toxic fragment beta A25-35 on the mitogen-induced rise in the intracellular calcium concentration ([Ca2+]i) in lymphocytes of AD (n = 13) and depressive patients (n = 14) as well as in healthy controls was therefore investigated (n = 16). The results showed a significant increase in the mitogen-induced calcium signal with lymphocytes of healthy controls and depressive patients. This beta A25-35-induced amplification was significantly lower in AD patients as compared to healthy controls but not as compared to depressive patients. The results thus confirm a postulated decreased beta-amyloid sensitivity in AD lymphocytes. However, this effect might not be as pronounced or as specific as recently described by Eckert et al., (1993b).

Aged↗
PubMed1995

[Computer-assisted individualized memory training in Alzheimer patients].

Memory training programs for cognitively impaired patients have often been criticized for their lack of relevance to everyday activities. We therefore report our experience with two patients suffering from probable Alzheimer's disease who were trained with a new computer-based program recently developed by our research group. An everyday task of personal relevance to the patient was simulated and trained on a PC touch screen using personal photographs of the patient's surroundings and biography. The patient's training performance (time, mistakes, number of advices) improved substantially. While psychopathometric tests showed no significant effects with regard to general cognitive performance, levels of motivation were high and there was a positive acceptance of the training, signs of emotional activation and of a transfer of the trained skills into real situations.

Activities of Daily Living↗
PubMed1994

Lateralization of the Bereitschaftspotential to the left hemisphere in patients with major depression.

Fourteen patients with major depression and 18 healthy subjects performed a Bereitschaftspotential (BP) paradigm, which required them to clench the right fist at self-paced intervals. The BP was calculated as the integrated negative amplitude from BP onset to movement onset. The latter was defined by recording the electromyogram (EMG) from the right forearm. To evaluate lateralization, the integrated BPs at C3, C4, P3, and P4 were analyzed. In depressives, a significant asymmetry of the BP to the left was found, whereas in normals the BP was nearly symmetrically distributed around the midline. Three patients were retested when clinically improved. At that time the asymmetry to the left hemisphere had nearly vanished. This asymmetry to the left hemisphere is interpreted as a cortical deactivation of the right cerebral hemisphere and seems to be a state marker of depression.

Adolescent↗
PubMed1994

[Prognosis of depression in the elderly].

Depressive syndromes are, with dementia, the most frequent psychiatric disorders in the elderly. The etiology of depressive syndromes can be reactive, endogenous, and neurotic as well as organic. Recent studies could show, that about 60% of the elderly patients clearly improve under treatment. Therefore the earlier opinion of a dramatically poorer outcome has to be revised. The presence of simultaneously occurring somatic illness, positive family history, certain personality traits and severity of disease could exert a bad influence on clinical outcome. Medical treatment should consider the special pharmacological features in higher age, and should be combined with psychotherapy as well as a close involvement of the relatives.

Aged↗
PubMed1994

Axonal transport of endogenous nerve growth factor (NGF) and NGF receptor in experimental diabetic neuropathy.

There is increasing evidence that deprivation of the retrogradely transported neurotrophic protein nerve growth factor (NGF) accounts for some functional deficits known to occur in experimental diabetic neuropathy. Here we have studied changes in the axonal transport of endogenous NGF, NGF receptor (NGFR), and NGFR saturation (NGF/NGFR ratio) in the rat sciatic nerve after 2 months of streptozotocin (STZ)-induced diabetes mellitus. Compared with vehicle-treated control rats (blood glucose: 6-12 mM), there was a very clear reduction in the retrograde transport of NGF by 50% (P < 0.001) in STZ-treated, diabetic animals (blood glucose: 33-62 mM). No significant reduction in NGF axonal transport was observed in a subpopulation of STZ-treated rats (poor responders) with nearly normal glucose levels (range: 9-12 mM). No change was observed in any group in the retrograde transport of NGFR. Compared with control rats, however, the apparent NGFR saturation was reduced by 45% (P < 0.002) in STZ diabetics, whereas no change in NGFR saturation was observed in the STZ-poor responders. Moreover, the NGFR saturation and amount of retrogradely transported NGF were negatively correlated to the individual glucose concentration in diabetics (r2 = 0.47 and 0.55, respectively; P < 0.0001). These findings indicate that, while NGFR expression is normal in the STZ-diabetic neuropathy model, the marked decrease in receptor saturation observed in diabetics may reflect low peripheral NGF levels, which in consequence leads to the apparent deprivation of neuronal NGF in diabetic rats.

Animals↗
PubMed1994

Cytosolic free [Ca2+] in mononuclear blood cells from demented patients and healthy controls.

There is increasing evidence that the neurodegenerative processes in Alzheimer's disease (AD) may be related to alterations in calcium homeostasis and that these metabolic changes are not necessarily restricted to the central nervous system. However, previous studies investigating [Ca2+]i in fibroblasts, lymphoblasts, platelets and lymphocytes of AD patients gave inconclusive results, since increase, decrease and no alteration in [Ca2+]i were found in AD patients compared with controls. With respect to the importance of establishing altered Ca2+ homeostasis in peripheral cells, we have investigated [Ca2+]i in circulating mononuclear cells of patients with AD, multi-infarct dementia, age-associated memory impairment and healthy controls. [Ca2+]i was evaluated using the fluorescent dye fura-2 before and during stimulation with phythaemagglutinin (PHA). In our study we failed to find major differences in resting [Ca2+]i and in response to stimulation with 25 micrograms/ml and 100 micrograms/ml PHA in cells of AD patients as compared with all other groups investigated. There was only a tendency towards a decrease in [Ca2+]i in AD after stimulation with PHA. Thus the present findings suggest that [Ca2+]i evaluation in mononuclear cells does not have diagnostic value in discriminating AD patients from other demented patients. However, there might be some difference in [Ca2+]i values between early- and late-onset AD, which could have pathophysiological importance.

Adult↗
PubMed1994

Clinical presentation of depression in the elderly.

Depressive syndromes and dementia are the most frequent psychiatric disorders in the elderly. Reactive depressive syndromes can be associated with the restriction of social competence due to increasing multi-morbidity, loneliness, social isolation, the consequences of retirement, interpersonal conflicts, and the loss of partners or close relatives. Endogenous depressive syndromes in the elderly are frequently combined with diffuse and changing somatic complaints, psychomotor restlessness and agitation. Furthermore, depressive syndromes can be caused by somatic illness, degenerative disorders, other organic diseases or certain drugs. The presence of simultaneously occurring somatic illness, positive family history, certain personality traits, and severity of disease could exert an adverse influence on clinical outcome. Medical treatment should consider the special pharmacological features of old age, and should be combined with psychotherapy as well as a close involvement of the relatives.

Aged↗
PubMed1993

Near infrared spectroscopy (NIRS): a new tool to study hemodynamic changes during activation of brain function in human adults.

In healthy human adults, cerebral concentrations of oxygenated hemoglobin ([HbO2]) and deoxygenated hemoglobin ([HbR]) were assessed during brain activation using near infrared spectroscopy (NIRS). Measurements were made either in the frontal cortex (n = 10) during performance of cognitive tasks or in the occipital cortex (n = 6) during visual stimulation (flash-light exposure, picture observation). The typical findings during brain activation were an increase in [HbO2] and a decrease in [HbR]. We demonstrate that these findings are not due to alterations in skin blood flow. NIRS is a simple bedside technique for the assessment of hemodynamic alterations accompanying brain activation.

Adult↗
PubMed1992

Nerve growth factor and choline acetyltransferase activity levels in the rat brain following experimental impairment of cerebral glucose and energy metabolism.

Intracerebroventricular (ICV) injection of streptozotocin (STZ) has been reported to impair cerebral glucose utilization and energy metabolism (Nitsch and Hoyer: Neurosci Lett, 128:199-202, 1991) and also to prejudice passive avoidance learning in adult rats (Mayer et al.: Brain Res 532:95-100, 1990). It is well established that the forebrain cholinergic system, whose integrity is essential for learning and memory functions, depends on the target-derived retrograde messenger nerve growth factor (NGF). Therefore, we measured NGF and choline acetyltransferase (ChAT) activity levels in the forebrain cholinergic system in adult rats that had received a single injection of either STZ or artificial cerebrospinal fluid into the left ventricle 1 or 3 weeks prior to sacrifice. One week after ICV STZ treatment, NGF content was significantly decreased (-32%) in the septal region, where NGF-responsive cell bodies are located and NGF exerts its neurotrophic action after retrograde transport from NGF-producing targets. In contrast, NGF levels in the cortex and hippocampus, which are target regions for the basal forebrain cholinergic neurons, and in the brainstem and cerebellum were increased (+12% to +47%) within 3 weeks after ICV STZ treatment. The alterations in NGF levels were not related to changes in ChAT activity that decreased in the hippocampus by only 15%. This might be due to masking effects exerted by compensatory NGF-mediated stimulation of ChAT activity in remaining functional neurons. It is suggested that impaired behavior which has been observed after STZ-induced impairment of cerebral glucose and energy metabolism may be at least partially related to a diminished capacity of central NGF-responsive neurons to bind and/or transport NGF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Diabetes mellitus-associated decrease in nerve growth factor levels is reversed by allogeneic pancreatic islet transplantation.

After an untreated 5-month duration of streptozotocin (STZ)-induced diabetes mellitus (DM), nerve growth factor (NGF) levels in BDE rats were decreased to 45-65% of control in the sympathetically innervated target organs iris and submandibular gland, in the superior cervical ganglion (containing NGF-dependent sympathetic perikarya projecting to the cranial targets), and in the NGF-transporting sciatic nerve. Successful allogeneic pancreatic islet transplantation (providing a physiological glucose homeostasis without immunosuppression) after 3-4 weeks of DM reversed the DM-related decrease in NGF levels 4 months after transplantation as compared with untreated diabetic rats. By contrast, NGF levels in the treated vas deferens (innervated by short postganglionic sympathetic neurons) remained increased as in the untreated diabetic rats (175% of control). Thus, DM-associated changes in endogenous NGF levels seem to be reversible by institution of metabolic control, at least at an early stage of DM when NGF-responsive neurons have not been deprived of NGF for a long time.

Animals↗