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R Heun

Publications and source records attributed to R Heun.

At least 19 recordsLinked to original sources

Decrease of N-acetylaspartate in the MTL correlates with cognitive decline of AD patients.

In this (1)H-MRS follow-up study of the medial temporal lobe (MTL) in patients with AD, the authors report a correlation of N-acetylaspartate (NAA)/creatine (Cr) with cognitive decline. Severely progressed patients showed a reduction, whereas stable or mildly progressed subjects showed a slight increase of NAA/Cr. The reduction of NAA/Cr in the MTL represents a correlate of cognitive deterioration in AD, whereas it is of limited use to detect subtle changes over time in clinically stable patients.

Aged↗

Amplitude reduction of the mismatch negativity in first-degree relatives of patients with schizophrenia.

First-degree relatives of schizophrenic patients display alterations in various cognitive domains and their electrophysiological counterparts similar to schizophrenic subjects. The mismatch negativity (MMN) is an event-related potential that reflects sensory memory in the pre-attentive stage of auditory processing. An amplitude reduction of the MMN has been reported in schizophrenia. The present study investigated the MMN in patients with schizophrenia, first-degree relatives and control subjects. The MMN amplitude was reduced in relatives compared to controls. The MMN amplitude reduction in schizophrenic patients compared to controls, however, did not reach significance in the present study. These results provide first evidence for disturbed sensory memory in relatives of patients with schizophrenia.

Adult↗

A family study of Alzheimer disease and early- and late-onset depression in elderly patients.

BACKGROUND: The substantial symptomatic overlap between depression and dementia in old age may be explained by common genetic vulnerability factors. METHODS: We investigated this idea by comparing the occurrence of both disorders in first-degree relatives of 78 patients with Alzheimer disease (AD), of 74 with late-onset depression (onset age of > or = 60 years), of 78 with early-onset depression, of 53 with comorbid lifetime diagnoses of AD/depression, and of 162 population control subjects. Diagnostic information on their 3002 relatives was obtained from structured direct assessments and from family history interviews. RESULTS: The 90-year lifetime incidence of primary progressive dementia was significantly higher in relatives of patients with AD (30%) and comorbid AD/depression (27%) than in relatives of patients with early-onset (21%) or late-onset (26%) depression, or of controls (22%) (P =.01). Lifetime incidence of depression was significantly higher in relatives of patients with early-onset depression (13%) than in relatives of patients with AD (10%) or controls (9.0%) (P =.006). Lifetime incidence of depression was similar in control relatives and in relatives of those patients with comorbid AD/depression (8.6%). Relatives of patients with late-onset depression also showed similar occurrence of depression until the age of 80 years, but the figure increased sharply thereafter to 19.1% by the age of 90 years. CONCLUSIONS: Primary progressive dementia and early-onset depression represent clinical entities with distinct inheritance. Late-onset depression does not share substantial inheritance in common with dementia or with early-onset depression, but does show modest familial clustering.

Age Factors↗

Seasonal distribution of births in patients with Alzheimer's disease and elderly depressive patients.

Winter births have been associated with a higher risk of Alzheimer's disease (AD) and other psychiatric disorders. In the present investigation, this putative association was examined in a sample of gerontopsychiatric patients. An analysis of the quarterly birth rates of 83 patients with AD, 78 elderly depressive patients with an early onset and 74 patients with a late onset of the depressive disorder, 48 patients with both AD and depression (co-morbid patients) and 107 healthy control subjects, revealed no particular seasonal distribution for any of the diagnostic groups. In AD and co-morbid patients, controlling for the ApoE genotype did not change this finding. Logistic regression analysis revealed the expected findings that increasing age and the presence of the ApoE4 allele were associated with a higher risk of dementia. Younger age and female gender were identified as risk factors for a depressive disorder. A winter birth (birth in the first three months of the year) was not associated with any of the diagnostic subgroups. We concluded that in our sample a seasonal distribution of births was not found to increase the risk for AD or geriatric depression.

Age Distribution↗

Encoding and retrieval related cerebral activation in continuous verbal recognition.

The differential neuronal activation related to encoding of novel and recognition of previously studied items and the effect of retrieval effort on neuronal activation were assessed in a event-related functional magnetic resonance imaging experiment. A verbal continuous recognition task with two repetitions of the target items was used. The interpretation of the results was focused on brain areas that have been previously reported to be involved in explicit memory. Encoding of novel words in comparison with the first repetition was associated with a stronger activation in the left parahippocampal and inferior frontal gyrus. Encoding of novel words compared to the second repetition was related to a greater bifrontal activation. Recognition of studied items was associated with greater activation in the medial and bilateral inferior parietal lobe at first repetition and in the medial and left inferior parietal lobe at second repetition in comparison with encoding of the novel items. Recognition at first repetition compared to recognition at second repetition was associated with greater bilateral frontal activation. The results are discussed in relation to current concepts of spatial differentiation of memory function and findings from event-related potentials studies of continuous recognition.

Adult↗

The factor structure in the cognitive battery of the structured interview for the diagnosis of dementia of the Alzheimer type, multi-infarct dementia, and dementias of other aetiology.

The Structured Interview for the Diagnosis of Dementia of the Alzheimer Type, MultiInfarct Dementia, and Dementias of Other Aetiology (SIDAM) includes the Mini-Mental State Examination extended by a number of additional items and allows the diagnosis of dementia according to ICD-10 and DSM-III-R criteria. The authors proposed to summarize selected items to form syndrome scores. These syndrome scores are supposed to measure different aspects of cognition. However, these syndrome scores have not been empirically confirmed. The present article presents a principal component analysis performed on the SIDAM test performances of 456 elderly subjects. The subjects were recruited in the course of a family study on dementia of the Alzheimer's type and depression in the elderly. One hundred four of these subjects met the criteria of dementia according to the ICD-10 criteria. Thus, the sample represents the population in which the SIDAM is frequently used in routine clinical and epidemiological studies. We found a six-factor structure accounting for 57.1% of the variance with some similarities to the predefined structure of different syndrome scores proposed by the authors of the SIDAM. The first factor found in principal component analysis represented different higher cortical functions that all depend on language and comprehension. Three factors covered three different aspects of memory, i.e., orientation for time, orientation for place, and short-term memory. One factor represented visuoconstructive skills and, finally, there was a factor representing intellectual abilities and education. This empirically found factor structure characterizes the dimensions of cognitive deficits in demented subjects measured by the SIDAM. Syndrome scores should reflect these dimensions. Consequently, we propose to consider the empirically found factor structure in a new version of the SIDAM.

Aged↗

Sensory gating deficit expressed by a disturbed suppression of the P50 event-related potential in patients with Alzheimer's disease.

OBJECTIVE: Disturbed sensory gating has been related to attention deficit and greater distractibility in patients with schizophrenia, and dysfunction of the alpha-7 subunit of the cholinergic nicotinic receptor has been discussed as its biological basis. Alzheimer's disease is characterized by a cholinergic deficit, and postmortem studies have reported alpha-7 receptor loss in patients with Alzheimer's disease. In this study, the authors tested whether sensory gating is disturbed in patients with Alzheimer's disease. METHOD: Suppression of the P50 event-related potential following the second click of a double-click paradigm, a measure of sensory gating, was assessed in 17 Alzheimer's disease patients and 17 comparison subjects. RESULTS: Alzheimer's disease patients showed less P50 suppression following the second click relative to the comparison subjects. CONCLUSIONS: Disturbed sensory gating might result from cholinergic dysfunction and possibly from alpha-7 nicotinic receptor loss in patients with Alzheimer's disease. Prospective studies should investigate the relationship between sensory gating deficit and behavioral disturbances in Alzheimer's disease patients.

Acoustic Stimulation↗

Identical distribution of the alpha 2-macroglobulin pentanucleotide deletion in subjects with Alzheimer disease and controls in a German population.

Recently, an association between a deletion polymorphism in the alpha 2-macroglobulin gene (A2M) and Alzheimer disease (AD) has been reported. The aim of the present study was to corroborate this association in a German population of 102 AD patients and two control samples of 191 healthy subject and 160 depressed patients. The frequency of the A2M genotype in AD patients was almost identical to that in both control samples. Logistic regression analysis revealed an effect of age and the APOE genotype on AD risk, but no effect of the A2M genotype. Our findings do not support the fact that the previously reported positive association between A2M deletion polymorphism and AD modifies the disease risk in the studied population. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:775-777, 2000.

Aged↗

Association between a functional polymorphism in the monoamine oxidase A gene promoter and major depressive disorder.

Various polymorphisms of the X-chromosomal monoamine oxidase A (MAO-A) gene were investigated for association with affective disorders. However, none of the studied variants could consistently be associated with either major depressive or bipolar affective disorder. Recently, a positive association between panic disorder and a novel functional repeat polymorphism in the MAO-A gene promoter, with the longer alleles being more active, was reported. Since monoaminergic neurotransmission is supposed to play an important role in affective disorders, we investigated a potential association of this polymorphism with major depressive illness in a sample of 146 unrelated patients of German descent and a control group of 101 individuals with a negative life history for affective disorders. Similarly to the recent findings in panic disorder, we observed a significantly increased frequency of genotypes containing only long alleles in female patients with recurrent major depression in comparison with age- and sex-matched controls. Thus, our data suggest that an excess of high-activity MAO-A gene promoter alleles resulting in an elevated MAO-A activity is a risk factor for major depressive disorder in females. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:801-803, 2000.

Adult↗

No association of serum levels of interleukin-6 and its soluble receptor components with a genetic variation in the 3'flanking region of the interleukin-6 gene in patients with multiple sclerosis.

Interleukin-6 (IL-6) plays an important role in the regulation of the inflammatory response in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Previous reports indicated that a variable number tandem repeat (vntr) polymorphism in the 3'flanking region of the IL-6 gene (C allele) is associated with altered activity of IL-6 in vivo. Therefore, we analyzed the frequency distribution of IL-6 gene C allele vntr poymorphism in 96 MS patients and 106 ethnically matched healthy controls. Moreover, possible correlations between genotypic differences of IL-6 gene and serum levels of IL-6, soluble IL-6 receptor (sIL6-R), soluble gp130 (sgp130), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were investigated. There were no differences in the allelic distribution of the IL-6 gene C allele between MS patients and healthy controls, and no association of the IL-6 gene C allele with serum levels of IL-6, sIL-6R, spg130, sICAM and sVCAM-1 was found.

Adolescent↗

Response-related fMRI analysis during encoding and retrieval revealed differences in cerebral activation by retrieval success.

The aim of the study was to identify cerebral activation associated with sufficient or insufficient encoding, and with correct or false recognition. Fourteen volunteers performed two paradigms: explicit learning of words; and later retrieval of previously presented words. Items were classified according to the subjects' recognition performance. Echo-planar MRI of blood-oxygen-level-dependent signal changes was performed during encoding and retrieval. Response-related fMRI-analysis was used to compare activation associated with the subjects' retrieval success. During encoding, there was a trend towards increased activation of the left medial cingulate gyrus and of the right fusiform gyrus for later hits (correctly identified, learned target words) in comparison with misses (non-identified targets). During recognition, signal intensities associated with false alarms (falsely identified distractors) were significantly higher in left and right extrastriate cortex than those associated with hits, misses and correct rejections of distractors. Activation in the anterior cingulate gyrus during retrieval was related to reaction time and might be associated with the preparation or performance of motor response. Increased activation during false alarms might reflect a source-monitoring deficit or an increased subjective familiarity with distractors that have been most intensively processed in extrastriate visual cortex.

Adult↗

Proton MR spectroscopy detects a relative decrease of N-acetylaspartate in the medial temporal lobe of patients with AD.

BACKGROUND: The reduction of N-acetylaspartate (NAA) detected by proton MR spectroscopy (1H-MRS) represents a robust but unspecific marker for neuronal loss or dysfunction. OBJECTIVE: To apply 1H-MRS in two brain regions that reflect the characteristic spatial distribution of neuronal loss in AD. These regions are the medial temporal lobe (MTL), which is affected early in AD, and the primary motor and sensory cortex (central region), which is affected late in the disease and might serve as an intraindividual control region in mild to moderate disease stages. METHODS: Twenty patients and 18 volunteers underwent 1H-MRS in both brain areas. The metabolic ratios of NAA/creatine and choline/creatine were determined. Additionally, the metabolic ratios of the MTL were divided by the ratios of the central region to assess the relative change in the MTL in individual subjects. All ratios were correlated with psychometric test scores. RESULTS: A significant reduction of NAA/creatine and choline/creatine ratios was detected in the MTL of patients with AD. In the central region, no significant difference between the groups was found. NAA/creatine (MTL/central region) was reduced in patients with AD and showed a correlation with the Mini-Mental State Examination and the cognitive part of the Alzheimer Disease Assessment Scale scores. Choline/creatine (MTL/central region) did not show a significant difference between groups. CONCLUSION: Assessing the distribution of NAA/creatine reduction guided by the expected neuropathologic change can improve the role of 1H-MRS in the assessment of AD. The disease severity can be monitored by relative reduction of NAA/creatine in the MTL in comparison with an intraindividual unaffected control region.

Aged↗

Allelic association between the D10S1423 marker and Alzheimer's disease in a German population.

Recently a full genome survey detected an allelic association between Alzheimer's disease (AD) and the D10S1423 marker on chromosome 10p12-14 (40 cM from the telomere). In this study we examined the D10S1423 marker in an ethnically homogeneous German population of 80 AD patients and two groups of controls, 168 healthy subjects and 149 depressed patients. The 234-bp allele of the D10S1423 marker showed a significant association with AD (P = 0.033). In conclusion, our results support that the D10S1423 marker is associated with an increased AD risk and provides further evidence for an AD susceptibility locus on chromosome 10.

Aged↗

Plasma 24S-hydroxycholesterol: a peripheral indicator of neuronal degeneration and potential state marker for Alzheimer's disease.

The conversion of brain cholesterol into 24S-hydroxycholesterol and its subsequent release into the periphery is probably an important step for the maintenance of brain cholesterol homeostasis. Recent findings suggest that plasma 24S-hydroxycholesterol may be elevated in Alzheimer's disease (AD) and vascular dementia at least at some stage of the disease, suggesting increased brain cholesterol turnover during neurodegeneration. We investigated whether plasma 24S-hydroxycholesterol concentrations depend on the severity of AD and on the apolipoprotein E (apoE) genotype. Severity of AD and inheritance of the apoE4 allele were independently associated with reduced plasma 24S-hydroxycholesterol/cholesterol ratios. The results suggest that the decrease of plasma 24S-hydroxycholesterol/cholesterol in severely affected AD patients is a peripheral marker for loss of cholesterol 24S-hydroxylase in the CNS. Inheritance of the apoE4 allele may be associated with increased apoE-mediated transport of brain cholesterol to the periphery or with decreased activity of the 24S-hydroxylase. Longitudinal studies will assess the validity of the ratio plasma 24S-hydroxycholesterol/cholesterol as a state marker for AD.

Aged↗

Association between an interleukin-6 promoter and 3' flanking region haplotype and reduced Alzheimer's disease risk in a German population.

Several studies have demonstrated that interleukin-6 (IL-6) is involved in the pathogenesis of Alzheimer's disease (AD). We previously reported on an association between the C allele of a variable number of tandem repeat polymorphism in the 3' flanking region of IL-6 gene (IL-6vntr) and delayed initial onset and reduced AD risk. A novel G/C polymorphism at position -174 in the IL-6 gene promoter (IL-6prom) has recently been identified and appears to influence the regulation of IL-6 expression. We examined this functional polymorphism in 102 AD patients and two control groups of 191 healthy subjects and 160 depressed patients. There was no evidence for an allelic association between IL-6prom polymorphism and earlier age of onset or risk of AD. However, haplotype analysis showed a strong linkage disequilibrium between IL-6vntr and IL-6prom and demonstrated an interaction between IL-6vntr and IL-6prom which modifies AD risk.

Alleles↗