Biomedical subjects

R Heun

Publications and source records attributed to R Heun.

119 records · Page 7Linked to original sources

PubMedDate not supplied

24S-hydroxycholesterol in cerebrospinal fluid is elevated in early stages of dementia.

The brain is the most cholesterol-rich organ in the human body. Accumulation of excess cholesterol in hippocampal neurons promotes the cleavage of the amyloid precursor protein (APP) into amyloidogenic components with the consequence of the acceleration of neuronal degeneration. Conversion of cholesterol to 24S-hydroxycholesterol mediated by cholesterol 24S-hydroxylase (CYP46) is the major pathway for the elimination of brain cholesterol and the maintenance of brain cholesterol homeostasis. We examined whether cerebrospinal fluid (CSF) 24S-hydroxycholesterol levels differ between patients with dementia, patients with mild cognitive impairment (MCI), and cognitively intact control subjects. Plasma and CSF concentrations of 24S-hydroxycholesterol and cholesterol in 32 patients with Alzheimer's disease (AD), 11 patients with vascular dementia, seven patients with MCI, and seven cognitively intact control subjects were measured by combined gas-chromatography/mass spectrometry. We show elevated concentrations of 24S-hydroxycholesterol in the CSF of AD patients and we interpret this finding as a consequence of increased cholesterol turnover in the central nervous system during neurodegeneration. The observed influence of the apolipoprotein E epsilon4 (APOE4) allele on CSF 24S-hydroxycholesterol concentrations with a gene-dosage effect suggests the existence of a link between the AD risk factor APOE4 and CNS cholesterol metabolism. The elevation of CSF 24S-hydroxycholesterol appears to occur early in the disease process, since patients with mild cognitive impairment had also increased CSF concentrations of this compound. We believe that the CSF concentration of 24S-hydroxycholesterol is altered in AD-related neurodegeneration and thus, CSF 24S-hydroxycholesterol may be a marker for monitoring the onset and progression of the disease.

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PubMedDate not supplied

CYP2D6 polymorphism and tardive dyskinesia in schizophrenic patients.

Antipsychotic drug-induced tardive dyskinesia (TD) is a serious problem during psychopharmacologic treatment of schizophrenic patients. In search of genetic factors contributing to TD, there is a lack of consensus regarding the role of the polymorphic isozyme cytochrome P450 CYP2D6, which is involved in the oxidative metabolism of antipsychotic drugs. In the present case-control study, we tested the putative influence of the CYP2D6 genotype on the development of TD. Out of 157 patients, 109 were retrospectively selected meeting DSM IV criteria for schizophrenia or schizoaffective disorder, and 50 of them persistently presenting with TD. Genotyping detected the functional allele CYP2D6 *1, the known major defective alleles CYP2D6 *3, *4, *5, *6, and gene duplication. According to their number of functional CYP2D6 alleles, subjects were divided into carriers of none, one, or at least two functional CYP2D6 alleles. The proportions of these categories did not differ between patients and an ethnically homogenous control population (n = 195, p = 0.99) or between patients with and without TD (p = 0.818). Schizophrenic patients were carriers of gene duplication more often than healthy probands, without revealing statistical significance (p = 0.10). Out of seven patients with gene duplication, three developed persistent TD. Furthermore, patients with and without TD were comparable according to age, age of onset, gender, and duration of illness, but subjects with TD had taken more lifetime chlorpromazine equivalents (CPZ) than had patients without TD (chi 2-test, Student's t-test). Forward as well as backward logistic regression analyses confirmed that the presence of TD was influenced by lifetime CPZ but not by age, age of onset, gender, duration of illness, or CYP2D6 genotype. In contrast to the relevance of lifetime CPZ, the lifetime dose of antipsychotic drugs known to be metabolized by CYP2D6 did not significantly influence the presence of TD. In conclusion, our results provide no evidence for the contribution of CYP2D6 genotype to the development of TD in schizophrenic patients receiving long-term antipsychotic medication.

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PubMedDate not supplied

Serial position effects in dementia of the Alzheimer type.

BACKGROUND: The aim of the present study was to analyse serial position effects for immediate and delayed free recall in patients with dementia of the Alzheimer type and controls. EXPERIMENT 1: 44 patients with dementia of the Alzheimer-type and 24 non-demented controls were asked for immediate and delayed free recall of 12 schematic drawings of common objects presented at the rate of 10 s/picture. Steep primacy effects were obtained at all delays in controls. By contrast, primacy effects were significantly impaired in patients with dementia at all delays of recall. Small immediate and delayed recall recency effects were found in both, patients and controls. EXPERIMENT 2: 19 patients with dementia of the Alzheimer type and 21 controls were asked for immediate and delayed free picture recall with presentation rates of 10, 5 and 1 s/picture. Again, primacy effects were significantly impaired in demented patients versus controls. With shorter presentation times, immediate recall recency effects were more pronounced than with longer presentation times, and no delayed recall recency effects were found. CONCLUSIONS: Primacy effect is impaired for immediate and delayed recall in dementia of the Alzheimer type. By contrast, immediate recall recency effect and possibly also long-term recency effect are preserved. The loss of the primacy effect contributes to the impairment of episodic memory in dementia of the Alzheimer type. Therefore further research is warranted into pharmacological and psychological interventions that might re-establish the primacy effect. Possibly, the orientation of demented patients might be improved by psychological techniques that rely on long-term recency effect.

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PubMedDate not supplied

Effect of presentation rate on word list learning in patients with dementia of the Alzheimer type.

The efficacy of simple interventions for the improvement of memory performance in patients with dementia of Alzheimer type (DAT) has rarely been evaluated. Therefore, we examined the effects of presentation duration and task practice on word list learning in this sample: 19 patients with DAT and 21 control subjects (with remitted major depression) repeatedly performed modifications of a word list learning task using five different presentation durations (i.e. 1, 2, 5, 10 or 20 s/word). In agreement with previous observations, prolonged visual presentation of words significantly improved recall and recognition in demented subjects, whereas task practice did not improve memory performance. The performance in the demented sample after long presentation times (20 s/item) does not reach the level of performance of the comparison group after short presentation times (1 s/item). Consequently, it seems unlikely that memory dysfunction is caused by increased item processing times in patients with dementia. To reach comparable performance of demented and controls for intervention or activation studies, presentation times must be shortened below 1 s/item in the control sample.

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PubMedDate not supplied

Early-onset and late-onset depression are independent of the genetic polymorphism of apolipoprotein E.

The recently shown association between apolipoprotein E (APOE) genotype and depressive illness has been challenged by subsequent studies. However, controversial results may derive from the different diagnostic criteria used for depression and from the small numbers of depressed patients included in the studies. We examined the association between depression and the genetic polymorphism of APOE in a large sample of depressed patients, Alzheimer's disease (AD) patients, and healthy controls following clear definitions for late-life depression. The cumulative incidence of depression depending on the age at onset of the first episode was examined by survival analysis. Our data do not disconfirm the hypothesis of depression sharing some common pathophysiologic features with AD, however, it seems very unlikely that the APOE genotype will elucidate the assumed common mechanisms.

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PubMedDate not supplied

Alpha-1-antichymotrypsin gene polymorphism and risk for sporadic Alzheimer's disease in a German population.

The A allele of a common A-T polymorphism in the signal peptide of alpha(1)-antichymotrypsin gene (ACT) has been reported to contribute a two- to threefold increased risk to Alzheimer's disease (AD) patients who carry the apolipoprotein E epsilon4 (APOE epsilon4) genotype. Since the ACT expression in AD brains is enhanced in particular in areas that develop amyloid plaques, the ACT polymorphism is considered to be a good candidate gene. We have analyzed this polymorphism in 102 AD patients and 191 matched controls, all originating from Western Germany. No statistically significant differences in allele frequencies and in genotype distribution of ACT could be shown between AD patients and controls. When we analyzed the polymorphism in APOE epsilon4 carriers, no overrepresentation in our AD group could be shown for the ACT*AA genotype carriers. Copyrightz1999S.KargerAG,Basel

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PubMedDate not supplied

Psychometric analysis of the selective reminding procedure in a sample from the general elderly population.

The selective reminding procedure (SRP) has been proposed for the assessment of distinct aspects of episodic memory, i.e. storage to and retrieval from short-term and long-term memory, item learning and list learning, and as dementia screening tool. In the present study SRP results were analysed in 256 probands from the general elderly population. SRP scores were highly intercorrelated, and principal component analysis yielded only one single factor. The SRP scores were moderately and not differentially correlated with immediate and delayed free recall and recognition and with verbal fluency. All SRP scores discriminated nondemented probands with episodic long-term memory impairment from those without. The MMSE performed significantly better than any SRP score in detecting dementia. The theory-based assumption that the SRP allows assessment of different, independent aspects of memory could not be validated. It is suggested that the SRP is a mixed measure of semantic memory, episodic long-term and short-term memory, and working memory, and that the different SRP scores do not allow to assess different memory functions. Thus, the SRP may neither be recommended for assessment of different subfunctions of memory nor for dementia screening.

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PubMedDate not supplied

Effect of repetition and inspection times on picture recall in patients with dementia of Alzheimer type.

The present study is part of a series of systematic studies intended to identify simple strategies of picture presentation to improve recall performance in demented subjects. The aims of this design were to examine the effects of elaboration by naming, 4-fold repetition and different inspection times on memory performance. 19 patients with senile dementia of Alzheimer type and 21 control subjects with remitted depression were included. Picture recall was examined using different presentation conditions on 5 consecutive days. The presentation conditions significantly influenced recall performance depending on the diagnosis and on the delay of recall. Naming of pictures did not improve later recall or recognition. In both groups repetition improved memory performance. Shorter presentation times deteriorated immediate and delayed memory performance in comparison with the control condition. Forgetting did not depend on picture inspection times in patients and control. This observation allows the use of different presentation times for further comparisons of interventions in patients and control. Even though we could provide evidence of some minor memory improvements after some interventions, i.e. prolonged inspection time and repetition, we suppose that the cognitive reserve capacity in demented subjects is limited and does not allow major memory improvements.

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PubMedDate not supplied

Amygdala-hippocampal atrophy and memory performance in dementia of Alzheimer type.

The aim of the present study was to examine the involvement of brain structures, especially the amygdala-hippocampal complex, in dementia of Alzheimer type (DAT), and to assess the relation of amygdala-hippocampal atrophy with memory dysfunction. 14 patients with DAT and 10 healthy age-matched controls were examined with different neuropsychologic tests including the UCLA-Auditory Verbal Learning Test. MRI was performed with a conventional 1.5-tesla scanner. Atrophy was found in many brain structures of demented subjects in comparison with healthy age-matched controls. The volumes of amygdala-hippocampal complexes and of the temporal lobes of demented subjects were more reduced than the total brain volume and other structures. Memory dysfunction was highly correlated with atrophy of the amygdala-hippocampal complexes and of the temporal lobes. Consequently, DAT seems to affect the amygdala-hippocampal complex and their related function (i.e. memory) more than other cerebral structures, but cerebral degeneration in DAT is not restricted to these structures.

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PubMedDate not supplied

Transcranial Doppler sonography in dementia of Alzheimer type.

The intention of this study was to examine the relation of clinical variables and cognitive dysfunction to cerebrovascular blood flow in a sample of patients with Alzheimer's disease without any sign or symptom of cardiovascular or cerebrovascular disease. The patients met DSM-III-R criteria for dementia of Alzheimer type. Blood flow velocities in the anterior, middle (MCA) and posterior cerebral arteries were recorded using transcranial Doppler sonography. Several psychometric tests including the Mini-Mental State Examination (MMSE) were performed. The patients' age correlated significantly with the systolic flow velocity in the left MCA (r = -0.57) explaining 24% of the total variance; there was a reduction of the mean flow velocity of 0.7 +/- 0.2 mm/s for every additional year. The MMSE correlated significantly with the systolic flow velocity in the left MCA (r = 0.62) explaining 29% of the total variance. The correlations of flow velocities with age indicate that even in very old patients there is a progressive reduction of cerebral blood flow velocities. The independent negative correlations of flow velocities with cognitive dysfunction indicate that there are progressive cerebrovascular flow reductions in the course of Alzheimer's disease. Both facts should be taken into account when Alzheimer patients are compared with other samples.

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PubMedDate not supplied

Visual memory in Alzheimer patients: effects of practice, retention interval and severity of cognitive decline.

The study was aimed at estimating the effect size of practice, retention interval and dementia severity on free recall performance in Alzheimer patients. Patients met DSM-III-R criteria for dementia of Alzheimer type. Different picture sets were presented on 4 days. The forgetting curves on different days were compared using ANOVA for repeated measurements. Practice had a minor, but significant negative effect on recall performance explaining 1% of the variance in recall performance. The retention interval varied between zero and 24 h explaining 23% of the total variance. Dementia severity explained 52% of the variance. For the development of memory improvement strategies in Alzheimer patients, the repeated measurement design using intraindividual comparisons seems more powerful than group comparisons.

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