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R Heun

Publications and source records attributed to R Heun.

At least 37 records · Page 2Linked to original sources
PubMed2002

The insulin gene VNTR polymorphism in Alzheimer's disease: results of a pilot study.

Insulin (INS) and insulin-like growth factors include different polypeptides involved in growth and development. Possibly they play a role in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). A variable number of tandem repeats (VNTR) polymorphism at the human INS 5'-flanking region consisting of three distinct allele classes has been shown to influence the tissue-specific expression of INS and the insulin-like growth factor 2 (IGF-2). Since alterations in the expression of INS or IGF-2 might be relevant in AD, we investigated the association between the INS VNTR polymorphism and the risk for AD. We found no association between the INS VNTR genotype and the risk for AD (p = 0.873). However, survival analysis revealed that class III homozygotes of the INS VNTR polymorphism had an earlier initial onset in patients suffering from early AD (p = 0.002). Our preliminary results suggest, that genetically determined alterations of the INS/IGF-2 metabolism might modify the course of AD. Further studies are warranted to confirm these data in larger study samples.

Age of Onset↗
PubMed2002

Fertility and number of children in patients with Alzheimer's disease.

Oestrogen therapy has been suggested to have protective effects against Alzheimer's disease. The effects of natural exposure to oestrogen in cognitive disorders have rarely been studied. Assuming that nulliparous women have a higher exposure to natural oestrogen, it could be hypothesised that these women might have a lower risk of Alzheimer's disease than women who have had children. The fertility and number of children in 106 women with a diagnosis of Alzheimer's disease was examined and compared with that of 189 female subjects from two control groups with subjects without dementia. As additional control, the same comparisons were carried out for 40 male patients with Alzheimer's disease and 105 male control subjects. In female subjects, having had children was found to be associated with a diagnosis of Alzheimer's disease. This was not the case in male subjects. The number of children did not seem to affect the risk of Alzheimer's disease, neither in female nor in male subjects. Natural exposure to oestrogen seems to reduce the risk of Alzheimer's disease in women.

Aged↗
PubMed2002

Possible influence of selection bias on gender differences in the risk of Alzheimer's disease.

For the observation of a higher risk of Alzheimer's disease (AD) in women, causes like a general longer life expectancy of women, a longer lifespan of women with AD, a later age at onset and a lower level of education compared with men have been discussed. However, methodological artefacts could also contribute to the observed gender difference. Data from a comprehensive family study was re-evaluated, in which a gender difference in the risk of AD had been observed. Available relatives had been directly interviewed, information on unavailable ones was provided by thirds. A differential, gender specific participation led to the under-representation of older and demented men, creating a selection bias, that may be the cause for the observed gender difference in the risk of AD. Study methods must be taken into account when interpreting information on gender differences in the risk of AD.

Aged↗
PubMed2002

Risk factors for new depressive episodes in primary health care: an international prospective 12-month follow-up study.

BACKGROUND: Studies that examined community samples have reported several risk factors for the development of depressive episodes. The few studies that have been performed on primary care samples were mostly cross-sectional. Most samples had originated from highly developed industrial countries. This is the first study that prospectively investigates the risk factors of depressive episodes in an international primary care sample. METHODS: A stratified primary care sample of initially non-depressed subjects (N = 2,445) from 15 centres from all over the world was examined for the presence or absence of a depressive episode (ICD-10) at the 12 month follow-up assessment. The initial measures addressed sociodemographic variables, psychological/psychiatric problems and social disability. Logistic regression analysis was carried out to determine their relationship with the development of new depressive episodes. RESULTS: At the 12-month follow-up, 44% of primary care patients met ICD-10 criteria for a depressive episode. Logistic regression analysis revealed that the recognition by the general practitioner as a psychiatric case, repeated suicidal thoughts, previous depressive episodes, the number of chronic organic diseases, poor general health, and a full or subthreshold ICD-10 disorder were related to the development of new depressive episodes. CONCLUSIONS: Psychological/psychiatric problems were found to play the most important role in the prediction of depressive episodes while sociodemographic variables were of lower importance. Differences compared with other studies might be due to our prospective design and possibly also to our culturally different sample. Applied stratification procedures, which resulted in a sample at high risk of developing depression, might be a limitation of our study.

Adolescent↗
PubMed2002

Polymorphism in the cholesterol 24S-hydroxylase gene is associated with Alzheimer's disease.

Cholesterol and 24S-hydroxycholesterol are involved in the pathogenesis of Alzheimer's disease (AD). Increased serum cholesterol concentrations have been detected in patients with AD. 24S-Hydroxycholesterol is the primary cholesterol elimination product of the brain and possesses neurotoxic properties in vitro. The enzyme catalyzing the conversion of cholesterol to 24S-hydroxycholesterol, cholesterol 24S-hydroxylase (CYP46), is mainly expressed in neurons. Concentrations of 24S-hydroxycholesterol in cerebrospinal fluid (CSF) and serum differ significantly between AD patients and non-demented subjects. To test the hypothesis if polymorphisms in the CYP46 gene might influence the function of the respective enzyme and thus cholesterol metabolism in the human brain, we screened for polymorphisms in 114 AD patients and 144 healthy controls. Two intronic single nucleotide polymorphisms were observed and their allelic distribution was investigated. In our study sample, carriers of the C allele of the IVS3+43C --> T polymorphism were more prevalent in the group of AD patients than in healthy controls, while another IVS2-150A --> G polymorphism did not show a significant association with AD. The CC genotype of the IVS3+43C --> T polymorphism was associated with an increased 24S-hydroxycholesterol/cholesterol ratio in the CSF of AD patients. Our results indicate that the CYP46 gene locus may predispose to AD by increasing the 24S-hydroxycholesterol/cholesterol ratio in the brain.

Aged↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

Identification of items which predict later development of depression in primary health care.

To improve recognition and treatment of depression in primary care it would be advantageous to have criteria for identification of later depression. Only a few studies were performed on primary care samples to examine risk factors for new depressive episodes. These were mostly cross-sectional and did not include psychiatric symptoms as possible predictors. This is the first one-year-follow-up study investigating prospectively psychiatric symptomatology as risk factors for depressive episodes in a primary care sample. An international primary care sample of initially non-depressed subjects (n = 2,445) was examined for the presence of depression (ICD-10) at follow-up. Initial measures addressed presence of psychiatric symptoms according to the CIDI-Primary Health Care Version and sociodemographic variables. Logistic regression analysis was carried out to determine the relationship with the development of new depressive episodes. After one year, 4.4% of primary care patients met ICD-10 criteria for a depressive episode. Logistic regression analysis revealed that symptoms of depression and physical, mainly pain-related symptoms were associated with depression at follow-up. General practitioners therefore should be careful in the consideration of depressive symptoms but also of somatic complaints which might precede depression or mask depressive symptomatology. The present results might be helpful for future development of prediction scales.

Adolescent↗
PubMed2001

Validity of the five-item WHO Well-Being Index (WHO-5) in an elderly population.

BACKGROUND: Depression has a high prevalence in the elderly population; however it often remains undetected. The WHO 5-item Well-Being Index (WHO-5) is a short screening instrument for the detection of depression in the general population, which has not yet been evaluated. The goals of the present study were: 1) to assess the internal and external validity of WHO-5 and 2) to compare the two recent versions of WHO-5. STUDY POPULATION AND METHODS: 367 subjects above 50 years of age were examined with the WHO-5. ICD-10 diagnoses were made using a structured interview (CIDI). The internal validity of the well-being index was evaluated by calculating Loevinger's and Mokken's homogeneity coefficients. External validity for detection of depression was evaluated by ROC analysis. RESULTS: The scale was sufficiently homogeneous (Loevinger's coefficient: version 1 = 0.38, version 2 = 0.47; Mokken coefficient > 0.3 in nearly all items). ROC analysis showed that both versions adequately detected depression. Version 1 additionally detected anxiety disorders, version 2 being more specific for detection of depression. CONCLUSION: The WHO-5 showed a good internal and external validity. The second version is a stronger scale and was more specific for the detection of depression. The WHO-5 is an useful instrument for identifying elderly subjects with depression.

Aged↗
PubMed2001

Inter-rater reliability of family history information on psychiatric disorders in relatives.

The family history method in psychiatric family studies is an important and necessary way of obtaining information on family members who are not available for personal interview. Studies on the validity of this method have shown that family history information on psychiatric disorders in relatives is neither accurate nor sensitive but highly specific. However, its inter-rater reliability has rarely been assessed, even though this is a prerequisite for adequate validity. In the present investigation we examined the inter-rater reliability of family history information obtained with a semi-structured and symptom-oriented interview. Forty informants were interviewed twice by two different raters within 3 and 20 days. The inter-rater reliability was found to be good for dementia (kappa=0.82, 95% CI=0.61-1.00), alcohol related disorders (kappa=0.93, 95% CI=0.80-1.00), for depressive disorders (kappa=0.72, 95% CI=0.42-1.00), anxiety disorders (kappa=0.75, 95% CI=0.41-1.00) and any psychiatric disorder (kappa=0.79, 95% CI=0.66-0.91). We concluded that the family history interview is a useful family study instrument that can be applied reliably by different raters for frequent psychiatric disorders.

Adult↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗