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Reinhard Heun

Publications and source records attributed to Reinhard Heun.

At least 19 recordsLinked to original sources
PubMed2005

A comparative study of the different N-acetylaspartate measures of the medial temporal lobe in Alzheimer's disease.

OBJECTIVE: To investigate group differences and correlations and to determine the sensitivity and specificity of different measures of the neuronal marker N-acetylaspartate (NAA) in the medial temporal lobe of Alzheimer's Disease (AD) patients. METHODS: The metabolic ratio NAA/creatine (Cr), the absolute concentration of NAA referenced against brain tissue (BT) water and NAA multiplied with the amount of BT in the proton magnetic resonance spectroscopy (1H-MRS) voxel were assessed in patients and healthy controls with a single-voxel 1H-MRS protocol. RESULTS: All measures were significantly lower in AD patients compared with controls. NAA/Cr and NAA correlated weakly, and there was no correlation of NAA with the amount of BT in the voxel. The highest specificity (87%) at a sensitivity of 80% was observed for NAA multiplied with the amount of BT in the voxel. There was no correlation of the MMSE with any of the NAA parameters. CONCLUSIONS: NAA/Cr does not reflect NAA concentration very well. NAA is not correlated with brain atrophy. The BT volume in the 1H-MRS voxel in combination with the concentration of NAA discriminates AD from healthy controls sufficiently.

Aged↗
PubMed2005

Risk factors and early signs of Alzheimer's disease in a family study sample. Risk of AD.

OBJECTIVE: Several predictors of Alzheimer's disease (AD) have been identified. However, the relevance and independent contribution of risk factors and of possible early signs such as mild cognitive impairment and subjective memory impairment on the development of AD has not been investigated prospectively in a cohort of non-demented elderly including first-degree relatives of AD subjects. METHOD: The development of AD was investigated in 757 non-demented elderly. Initial diagnoses were made from personal interviews. Information on 633 subjects after 4.7 +/- 1.2 years (mean +/- SD) was obtained either from personal or family history interviews. Using forward logistic regression analysis, predictors were identified by comparing their presence in 38 subjects who developed AD and 577 subjects who remained non-demented. RESULTS: The most important predictors of later Alzheimer's disease were increased age (Odds ratio OR = 1.086/additional year, p < 0.001), initial subjective memory complaints (OR = 2.68, p = 0.019), initial mild cognitive impairment (OR = 2.51, p = 0.032) and female gender (OR = 2.84, p = 0.069). Exploratory analysis revealed that previous depression after the age of 60 years (OR = 2.37, p = 0.033) and the presence of the apolipoprotein E4 allele (OR = 2.49, p = 0.043) individually predicted new AD during follow-up. A positive family history of AD (i. e. being a first degree relative of a subject suffering from AD) did not significantly influence the development of AD (p > 0.2). CONCLUSIONS: Increased age, the presence of mild cognitive impairment, subjective memory impairment and gender are the most relevant independent predictors of later Alzheimer's disease that may be used in combination for clinical prediction of AD.

Age Factors↗
PubMed2005

The power of sample size and homogenous sampling: association between the 5-HTTLPR serotonin transporter polymorphism and major depressive disorder.

BACKGROUND: Several lines of evidence indicate that abnormalities in the functioning of the central serotonergic system are involved in the pathogenesis of affective illness. A 44-base-pair insertion/deletion polymorphism in the 5' regulatory region of the serotonin transporter gene (5-HTTLPR), which influences expression of the serotonin transporter, has been the focus of intensive research since an initial report on an association between 5-HTTLPR and depression-related personality traits. Consistently replicated evidence for an involvement of this polymorphism in the etiology of mood disorders, particularly in major depressive disorder (MDD), remains scant. METHODS: We assessed a potential association between 5-HTTLPR and MDD, using the largest reported sample to date (466 patients, 836 control subjects). Individuals were all of German descent. Patients were systematically recruited from consecutive inpatient admissions. Control subjects were drawn from random lists of the local Census Bureau and screened for psychiatric disorders. RESULTS: The short allele of 5-HTTLPR was significantly more frequent in patients than in control subjects (45.5% vs. 39.9%; p = .006; odds ratio = 1.26). CONCLUSIONS: These results support an involvement of 5-HTTLPR in the etiology of MDD. They also demonstrate that the detection of small genetic effects requires very large and homogenous samples.

Adult↗
PubMed2005

Suicide attempts in schizophrenia and affective disorders with relation to some specific demographical and clinical characteristics.

Demographical and clinical characteristics have been reported to modulate the risk for suicide. This study analysed demographical and clinical characteristics with respect to lifetime suicide attempts in 500 individuals affected with schizophrenic or affective disorders. Suicide attempts were associated with poor premorbid social adjustment, low age at onset, low scores on the "Global Assessment Scale" and childlessness in females.

Adult↗
PubMed2005

Risk factors of major depression in the elderly.

BACKGROUND: Several risk factors of depression have been identified in retrospective as well as some prospective studies in the elderly. Confirmation in independent samples is needed. The present follow-up study prospectively investigated risk factors of depression in an elderly German sample. METHODS: One thousand four hundred and thirty-one subjects from a family study were re-investigated after 4.7 +/- 2.5 years. Bivariate and multivariate forward logistic regression analyses were used to identify risk factors of the development of new depression in the elderly. RESULTS: Risk factors of a new depressive episode in 1408 elderly without current depression were age, female gender, a previous depression, subjective memory impairment, previous anxiety and somatoform disorders. The presence of dementia or mild cognitive impairment were significant risk factors in bivariate, but not multivariate analysis controlling for possible confounding. Risk factors of a first geriatric depressive episode were age, gender and subjective memory impairment; age remained the only significant risk factor in multivariate analysis. CONCLUSIONS: This investigation confirms previous studies from other countries concerning the relevance of risk factors for depression in the elderly. The knowledge of risk factors might help identify subjects at increased risk of depression for early intervention approaches. Elderly with a history of previous depression carry the highest risk.

Age Distribution↗
PubMed2004

Differences of cerebral activation between superior and inferior learners during motor sequence encoding and retrieval.

Cerebral activation during memory encoding and retrieval might depend on subjects' learning capacity, either by corresponding to better performance in superior learners or by reflecting increased effort in inferior learners. To investigate these alternative hypotheses, the study compared cerebral activation during encoding and retrieval of a motor sequence in groups of subjects with superior and inferior learning performances. Ten healthy subjects underwent functional magnetic resonance imaging (fMRI) while performing a motor sequence encoding paradigm (i.e. finger tapping sequence) and a retrieval paradigm (i.e. reproduction of the learned sequence). Subjects were divided into superior and inferior learners according to the correctness of sequence reproduction during retrieval. During encoding, there was strong bilateral activation in the middle frontal gyrus, the supplementary motor area (SMA), the lateral parietal lobe and the cerebellum. During retrieval, again strong activation was found in identical areas of the prefrontal cortex, the parietal lobe and the cerebellum. During encoding, inferior learners showed more left-sided activations in the left middle frontal and inferior parietal gyri. Superior learners showed increased activation in the corresponding right-sided brain areas during encoding as well as during retrieval. Differences of cerebral activations in the prefrontal and parietal cortex during encoding and retrieval were found to be related to retrieval performance, i.e. success and effort. Further intervention studies are needed to assess whether these interindividual differences are the cause or the consequence of differences in memory performance.

Achievement↗
PubMed2004

SREBP-1a polymorphism influences the risk of Alzheimer's disease in carriers of the ApoE4 allele.

Sterol regulatory element-binding proteins (SREBPs) are transcription factors involved in cholesterol and fatty acid synthesis. Recently, a polymorphism in the 5'-region of the SREBP-1a gene has been described to be correlated with alterations in the plasma levels of cholesterol. Consequently the relationship between this SREBP-1a gene polymorphism and Alzheimer's disease (AD) alone and in combination with the apolipoprotein E (ApoE) 4 allele was evaluated. No association between SREBP-1a polymorphism alone and AD could be seen. However, in the group of healthy ApoE4 allele carriers, the number of homozygote SREBP-1a DeltaG allele carriers was significantly higher than in AD patients. Cerebrospinal fluid levels of cholesterol were lower in AD patients who were carriers of the SREBP-1a DeltaG allele, and the ratio of 24S-hydroxycholesterol to cholesterol was increased in these probands. Our data suggest a reduced risk of AD in carriers of an ApoE4 allele who are additionally homozygous for the SREBP-1a DeltaG allele, which is possibly due to the influence of SREBP-1a polymorphism on brain cholesterol metabolism. This is the first report on a genetic factor which prevents the deleterious effect of the ApoE4 allele and thus reduces the risk of AD.

Aged↗
PubMed2004

Contribution of apolipoprotein E and cathepsin D genotypes to the familial aggregation of Alzheimer's disease.

OBJECTIVE: The familial aggregation of late-onset Alzheimer's disease (AD) might be caused by the clustering of genetic risk factors in families. This study investigates the influence of variants of candidate genes on the familial aggregation of AD. METHODS: The occurrence of AD was examined in 1,420 first-degree relatives of 70 AD patients and 144 nondemented controls classified by the presence of AD and relevant candidate genes in index subjects. RESULTS: Relatives of nondemented controls with an apolipoprotein E4 or a cathepsin D T allele had a higher cumulative lifetime incidence of AD than relatives of subjects without the respective alleles. This effect was not detected in relatives of AD patients. Variants of the interleukin-6, bleomycin hydrolase and alpha(2)-macroglobulin genes did not significantly influence the (age-adjusted) risk of AD in relatives. CONCLUSIONS: Familial aggregation of late-onset AD is likely to be caused by several genetic risk factors. Variants of the apolipoprotein E and cathepsin D genes influenced the risk of AD in relatives of nondemented control subjects. The lack of an influence of these genotypes on the risk of AD in relatives of AD subjects may be the consequence of complementary reductions of other genetic risk factors such as various, yet unknown susceptibility genes in patients and, consequently, in their first-degree relatives.

Aged↗
PubMed2004

No evidence for a genetic relationship between Alzheimer's disease and longevity.

OBJECTIVE: Late onset Alzheimer's disease (AD) is frequent in subjects who have reached an age above the average life expectancy. AD and life expectancy are both influenced by genetic factors. Consequently, a possible genetic relationship between AD and longevity was investigated using family study data. METHODS: First-degree relatives of patients with AD (n = 645) and of non-demented controls (n = 1,106) were examined by direct interview or by family history in the case of already deceased or unavailable subjects. Survival of subjects with an assumed familial load for AD (i.e. first-degree relatives of AD patients) and of controls was compared using the Kaplan-Meier analysis and log-rank statistics. RESULTS: Relatives with AD reached higher ages than other family members. However, there was no significant co-aggregation of AD and longevity in first-degree relatives of AD patients in comparison with those of controls. This applied to all diseased as well as non-demented relatives. CONCLUSIONS: Longevity is an independent prerequisite for the development of the disease, but is not genetically related to AD. The apparent longevity in relatives with AD is likely to result from the selection of subjects fulfilling this prerequisite.

Age Factors↗
PubMed2004

Response-related fMRI of veridical and false recognition of words.

OBJECTIVES: Studies on the relation between local cerebral activation and retrieval success usually compared high and low performance conditions, and thus showed performance-related activation of different brain areas. Only a few studies directly compared signal intensities of different response categories during retrieval. During verbal recognition, we recently observed increased parieto-occipital activation related to false alarms. The present study intends to replicate and extend this observation by investigating common and differential activation by veridical and false recognition. METHODS: Fifteen healthy volunteers performed a verbal recognition paradigm using 160 learned target and 160 new distractor words. The subjects had to indicate whether they had learned the word before or not. Echo-planar MRI of blood-oxygen-level-dependent signal changes was performed during this recognition task. Words were classified post hoc according to the subjects' responses, i.e. hits, false alarms, correct rejections and misses. Response-related fMRI-analysis was used to compare activation associated with the subjects' recognition success, i.e. signal intensities related to the presentation of words were compared by the above-mentioned four response types. RESULTS: During recognition, all word categories showed increased bilateral activation of the inferior frontal gyrus, the inferior temporal gyrus, the occipital lobe and the brainstem in comparison with the control condition. Hits and false alarms activated several areas including the left medial and lateral parieto-occipital cortex in comparison with subjectively unknown items, i.e. correct rejections and misses. Hits showed more pronounced activation in the medial, false alarms in the lateral parts of the left parieto-occipital cortex. CONCLUSIONS: Veridical and false recognition show common as well as different areas of cerebral activation in the left parieto-occipital lobe: increased activation of the medial parietal cortex by hits may correspond to true recognition, increased activation of the parieto-occipital cortex by false alarms may correspond to familiarity decisions. Further studies are needed to investigate the reasons for false decisions in healthy subjects and patients with memory problems.

Adult↗
PubMed2004

Identification of somatic and anxiety symptoms which contribute to the detection of depression in primary health care.

Somatic symptoms and anxiety symptoms are often disregarded in the detection of depression in primary care. The present investigation examined to what extent somatic and anxiety symptoms recorded with the Composite International Diagnostic Interview-Primary Health Care Version (CIDI-PHC) can improve the detection of depression as compared to the General Health Questionnaire-12-item version alone. Data from the World Health Organization study on Psychological Problems in General Health Care were used. The study sample consisted of primary care attenders from 15 centres from all over the world who underwent a psychiatric examination with the CIDI-PHC. Medically unexplained somatic symptoms (back pain, feelings of heaviness/lightness in parts of the body, periods of bodily weakness, seizures/convulsions, permanent tiredness, exhaustion after a minimum of effort) and-to a smaller extent-diverse anxiety symptoms (e.g. feelings of anxiousness/nervousness, feelings of tension, difficulties relaxing) significantly contributed to the detection of depression in a logistic regression analysis. The results confirm the observation that in primary care somatic symptoms play an important role in the manifestation of depressive disorders. The items investigated herein could prove beneficial for future depression screening instruments to improve the detection of depressive disorders in primary care.

Anxiety Disorders↗
PubMed2004

Mixed anxiety-depression in a 1 year follow-up study: shift to other diagnoses or remission?

BACKGROUND: In 1992, the ICD-10 introduced the concept of mixed anxiety-depression disorder (MAD). However, a study examining the stability of this ICD-10-diagnosis is lacking. Our objective was to examine the 12 month outcome of MAD in comparison to the outcome of depression, anxiety, and comorbid depression and anxiety. METHODS: 85 MAD patients, 496 patients with major depression, 296 patients with anxiety disorders, and 306 comorbid patients were reassessed after 12 months. Rates of depression, anxiety, and MAD were compared using chi(2)-tests. RESULTS: While depressive disorders and anxiety disorders showed relatively high stability, MAD Patients had no higher rates of MAD at follow-up than patients with depression, anxiety or both. LIMITATIONS: Detailed information regarding treatment and disorders during the follow-up interval was lacking. Prevalence rates of MAD in single centres were too small for contrasting centres. CONCLUSIONS: MAD cannot be seen as a stable diagnosis: Most of MAD patients remit; many of them shift to other diagnoses than depression or anxiety. The ICD-10 criteria have to be specified more exactly.

Adult↗
PubMed2004

Putative association of polymorphism in the mannose 6-phosphate receptor gene with major depression and Alzheimer's disease.

The endosomal lysosomal system might play a role in Alzheimer's disease, but its impact in major depression is unknown. The expression of the cation-dependent mannose 6-phosphate receptor (CD-MPR) is increased in Alzheimer's disease and the CD-MPR gene is located next to a region on chromosome 12 possibly linked to Alzheimer's disease. We investigated a C/T polymorphism in the CD-MPR gene in 188 Alzheimer's disease patients, in a control sample of 193 patients with major depression, as hospitalized controls, and in 259 healthy controls. We examined the interaction of the CD-MPR polymorphism with the putative risk factor for Alzheimer's disease, the cathepsin D T-allele. No significant association of the CD-MPR C-allele with Alzheimer's disease was observed. However, exploratory data analysis revealed an increased frequency of the CD-MPR C-allele in patients with major depression; thus, the C-allele may be a risk factor for depression. Gene location and function of the CD-MPR suggest an involvement in Alzheimer's disease; however, we could not find an association of the CD-MPR polymorphism with Alzheimer's disease. Since exploratory data suggest an involvement of the endosomal lysosomal system in major depression, further studies are warranted to investigate the biological role of the CD-MPR in major depression.

Aged↗
PubMed2004

The effects of gender and CYP46 and apo E polymorphism on 24S-hydroxycholesterol levels in Alzheimer's patients treated with statins.

To examine the effect of gender and polymorphisms of CYP46 and apo E on plasma levels of 24S-hydroxycholesterol in Alzheimer's disease (AD) patients and to determine whether these factors contribute to the variability in responses to statin treatment. Fifty-three AD patients had measurement of plasma levels of 24S-hydroxycholesterol, plasma and lipoprotein cholesterol and genotyping of CYP46 and apo E. Thirty-nine of the subjects subsequently participated in a statin trial for 6 weeks, and had a repetition of the baseline measurements. Baseline levels of 24S-hydroxycholesterol were higher in women than in men. There was a positive and significant correlation of plasma oxysterol levels with levels of total plasma cholesterol (women: r = .72, P < .0001; men: r = .47, P = .02) and non-HDL cholesterol (women: r = .68, P < .0001; men: r = 0.51, P = .01) (and LDL cholesterol) but not HDL cholesterol levels. There was no association of CYP46 or apo E polymorphisms with plasma levels of 24S-hydroxycholesterol. AD subjects treated with statins had a similar percent reduction in lathosterol, 24S-hydroxycholesterol, total cholesterol and non-HDL (and LDL) cholesterol regardless of gender and polymorphisms of CYP46. Subjects with the 4/4 polymorphism had less reduction in the ratios of 24S-hydroxycholesterol-LDL cholesterol. Women with AD had higher levels of plasma 24S-hydroxycholesterol levels than men. Women also showed a very strong correlation of plasma levels of 24S-hydroxycholesterol-to-total and non-HDL cholesterol. This may suggest that the oxysterol may be an important marker of AD risk instead of total cholesterol, as suggested by others. Polymorphisms of CYP46 or apo E do not explain levels of oxysterol or non-HDL cholesterol or the responsiveness to statin treatment in this study.

Aged↗
PubMed2003

Association of the C766T polymorphism of the low-density lipoprotein receptor-related protein gene with Alzheimer's disease.

The low-density lipoprotein receptor-related protein (LRP) is one of the most important cholesterol receptors in the brain. Gene variation of its ligand, apolipoprotein E, is a major genetic risk-factor for Alzheimer's disease (AD). The C-allele of the silent C766T polymorphism in exon 3 of the LRP gene might be associated with AD, however, results are conflicting and thus discussed controversially. Consequently, we compared the prevalence of this polymorphism in a homogenous cohort of patients with AD and control subjects. We found that carriers of a C-allele were at lower risk of AD; in agreement with this observation, AD patients who were carriers of a C-allele presented with a later age at onset of the disease than carriers of the TT genotype. These data suggest that LRP polymorphism influences the risk as well as the age at onset of AD. Our results contrast with other studies which described the C-allele to be a risk-factor for AD, but are in line with a recent publication on the effect of LRP polymorphism on longevity and on the risk for coronary artery disease. Further research on LRP polymorphisms is needed to evaluate their effects on the risk of AD, on coronary artery disease and on longevity.

Alzheimer Disease↗
PubMed2003

Polymorphism in the BACE gene influences the risk for Alzheimer's disease.

Pathological characteristics of Alzheimer's disease (AD) are neurofibrillary tangles and amyloid-beta (Abeta) plaques. Abeta is generated by cleavage of the amyloid precursor protein by beta- and gamma-secretases. BACE (beta-site APP cleaving enzyme) was identified as the beta-secretase. Variations of the BACE gene might influence activity and function of the protein and, thus, might influence the pathogenesis of AD. Consequently, we investigated the association of different BACE polymorphisms with AD. BACE exon 5 polymorphism influenced the risk of AD. This effect was most pronounced in apolipoprotein E4 allele carriers. Furthermore, Abeta(42) CSF levels were influenced by BACE genotype. It appears that BACE polymorphism plays a more important role in the development of AD than previously assumed, possibly by influencing Abeta(42) levels.

Adult↗
PubMed2003

Lifetime depressive and somatic symptoms as preclinical markers of late-onset depression.

BACKGROUND: Several risk factors of depression, i. e., female gender and life-stress, have been identified. Few studies have focussed on symptoms as preclinical markers of depression. In these studies current symptoms like dysphoria, tiredness and increased appetite predicted later depression. Even though of possible interest for treatment, no study focussed on lifetime symptoms as preclinical markers of depression. Consequently, we examined lifetime depressive and somatic symptoms with respect to later development of late-onset depression. METHODS: 664 non-depressed elderly subjects without lifetime diagnoses of depression at the initial examination were selected for a prospective follow-up study (mean follow-up +/- SD: 5.02 +/- 2.44 years). 51 subjects (mean age +/- SD: 66.6 +/- 11.3) developing late-onset depression (defined as depression starting after age 60) were compared to those remaining non-depressed (mean age +/- SD: 59.1 +/- 16.0) during follow-up using the CIDI. To determine the influence of lifetime symptoms on the development of depression, chi-square statistics and multivariate logistic regression analyses were performed. RESULTS: The following symptoms being present over a period longer than two weeks were individual preclinical markers of late-onset depression: dysphoria, increased appetite, insomnia, lack of energy, morning depth, lack of joy and interest, inferiority feeling, lack of self-confidence, poor concentration, indecisiveness, thinking about death, wish to die and joint pain. The most important symptoms elevating the risk of late-onset depression in a multivariate model were lack of joy and interest, poor concentration, increased appetite, lack of energy and joint pain. CONCLUSIONS: Different symptoms can be used individually and in combination to predict later depression. This might allow early treatment.

Age of Onset↗