Biomedical subjects

Reinhard Heun

Publications and source records attributed to Reinhard Heun.

48 records · Page 3Linked to original sources

PubMed2003

Subjective memory complaints of family members of patients with Alzheimer's disease and depression.

BACKGROUND: First-degree relatives of patients with Alzheimer's disease (AD) and major depression (MD) carry an increased genetic risk for the same disorders. Subjective memory complaints of the family members of patients might be an early sign or an indicator of an increased risk of either dementia or depression. Alternatively, they might be the consequence of the increased subjective awareness of relatives and spouses of patients of their own age-associated memory failures. To investigate the relevance of the above-mentioned hypotheses, the prevalence rates of subjective memory complaints of first-degree relatives and spouses of patients with AD, of patients with MD and of control subjects were compared. METHODS: Personal interviews were conducted with 718 first-degree relatives and 196 spouses of 146 AD patients, 168 patients with MD and 136 control subjects from the general population. The prevalences of subjective memory complaints by relatives or spouses were compared using chi(2) tests. To control for differences of gender and age at onset, Cox proportional hazards analyses were performed. RESULTS: There were no differences in the prevalence of subjective memory complaints by first-degree relatives of subjects with AD, MD and controls after controlling for age differences. The same applies to the subjective memory complaints in their spouses. CONCLUSION: Subjective memory complaints were frequent in family members. However, they were neither associated with the genetic risk of AD or of MD nor could they be explained by an increased awareness by having a demented spouse or relative. Consequently, familial factors seem to have a limited influence on the presence of subjective memory complaints in the elderly.

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PubMed2003

Reduced hippocampal activation during encoding and recognition of words in schizophrenia patients.

OBJECTIVE: In patients with schizophrenia, impaired hippocampal activation either during encoding or recognition tasks has been observed in a few functional imaging experiments. In this fMRI study, the authors report results of word encoding and recognition in schizophrenia patients and healthy comparison subjects, with a special focus on correcting for behavioral recognition success in order to prevent a bias related to lower task performance in the schizophrenia patients. METHOD: The verbal encoding and recognition tasks were both first analyzed irrespective of recognition success. In a second analysis, recognition success was included in the block-designed encoding task as a covariate of no interest, and incorrectly classified items were rejected from the analysis of the event-related recognition task. RESULTS: Patients performed poorer on the recognition task than the comparison subjects. Bilateral hippocampal activation during encoding and recognition was observed in both groups. Right hippocampal activation in patients during recognition became significant only after exclusion of wrongly classified items. Group comparison revealed greater activation in the healthy comparison subjects in the left anterior hippocampus during encoding and bilaterally during recognition. Greater bilateral hippocampal activation in the healthy subjects and greater activation in the right anterior hippocampus in the schizophrenic patients were revealed after presentation of novel words, which were intermixed with previously encoded words in the recognition task. After exclusion of incorrectly classified items, the differences in the right hippocampus remained significant. CONCLUSIONS: This study provides evidence for disturbed hippocampal function during verbal encoding and recognition in patients with schizophrenia. It extends previous studies by correcting for the possible confound of differences in behavioral task performance. This approach further supports the concept of hippocampal dysfunction in schizophrenia.

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PubMed2003

Association of an interleukin-1beta gene polymorphism at position -511 with Alzheimer's disease.

Inflammation is thought to promote neuronal cell death in Alzheimer's disease (AD). The proinflammatory interleukin-1 is a main component in inflammatory pathways and is overexpressed in the brain of AD patients. Investigation of different polymorphisms in the interleukin-1 genes (IL-1alpha -889, IL-1beta -511, IL-1beta +3953) revealed associations between specific alleles and AD in that they increased the risk or modified the age at onset of AD. However, there are controversial findings from other studies which revealed no significant associations between these polymorphisms and AD; thus further evaluation of the association of IL-1 gene polymorphisms with AD and their role in pathogenesis is needed. In this study we examined the distribution of the IL-1beta -511 alleles in AD patients and a control sample of healthy individuals. An additional control population of non-demented depressive inpatients was recruited to exclude a confounding bias. The cerebrospinal fluid (CSF) levels of Abeta42 in AD patients were investigated to assess the influence of IL-1beta -511 genotypes. We found no significant association of the IL-1beta -511 polymorphism with AD, suggesting that the IL-1beta -511 polymorphism is no risk factor for AD. However, we found the Abeta42 CSF levels to be lower in carriers of the IL-1beta CC-genotype compared to carriers of the T-allele. Even though IL-1beta -511 polymorphism did not influence the risk of AD it might have a pathophysiological influence on the disease process.

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PubMed2002

Identification of a single nucleotide polymorphism in the choline acetyltransferase gene associated with Alzheimer's disease.

The dysfunction of the cholinergic system in Alzheimer's disease (AD) supports the hypothesis that a decline in choline acetyltransferase (ChAT) activity in memory as well as in cognitive functions in AD might be functionally linked. To assess the physiological relevance of an allelic variation in the ChAT gene we investigated the presence of a possible polymorphism in AD patients and in elderly non-demented subjects as controls. By using polymerase chain reaction, single stranded conformation polymorphism or the LightCycler analysis we detected a single nucleotide polymorphism in the first common coding exon of the ChAT gene. We found a G --> A transition which occurred at position +4 of the coding sequence. The association between AD and the AA genotype or A alleles were found to be significant (odds ratio 3.7 and 2.4, respectively). The frequency of the AA genotype was three times higher in AD patients than in age-matched controls. This G --> A change raises the possibility that it may influence ATG usage resulting in attenuation of translation efficacy of ChAT messenger RNA. We suggest that such a polymorphism might be one of the events conferring an increased risk for deterioration of memory and cognition functions in AD.

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PubMed2002

The dichotomy of schizophrenia and affective disorders in extended pedigrees.

The paper reports the first controlled family study investigating not only 1st but also 2nd and 3rd degree relatives of patients with schizophrenia by direct diagnostic interviews. Regardless of their degree of relationship, all biological relatives of the patients were found to be at an elevated risk of schizophrenia (5.0% in 1st, 3.1% in 2nd, 1.5% in 3rd degree relatives compared to 0.8% among controls). Schizoaffective and affective disorders have also been found to be more common in the three groups of relatives but without a monotone decline of prevalence rates across the groups. Other psychiatric disorders were not found to be at an elevated risk in relatives of patients compared to controls. Thus, our findings support the hypothesis that psychotic, as well as affective disorders, aggregate in families of individuals with schizophrenia.However, in our study, the risk of schizophrenia and the risk of affective disorders correlated. Particularly, the magnitude of the risk of schizophrenia among relatives of probands with schizophrenia varied with the occurrence of affective disorders in relatives. In relatives, the risk of schizophrenia was maximal in absence of a family history of affective disorder. This constellation holds true even if only families of index cases without any affective syndrome during lifetime are considered.

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PubMed2002

Cerebrospinal fluid levels of beta-amyloid(42) in patients with Alzheimer's disease are related to the exon 2 polymorphism of the cathepsin D gene.

The intracellular aspartyl protease cathepsin D (catD) is involved in such Alzheimer's disease (AD)-related processes as the activation of the endosomal/lysosomal system and the cleavage of the amyloid precursor protein into amyloidogenic components, which may initiate neurodegeneration. A non-synonymous polymorphism (exon 2, C to T exchange leading to ala-->val substitution) of the gene encoding catD (CTSD) was previously associated with AD, in that the T allele increased the risk for AD. To investigate whether the T allele is associated with disease-related traits, we measured the concentration of the amyloid beta-peptide 1-42 (Abeta(42)) and 1-40 (Abeta(40)) in patients and control subjects. The T allele of the CTSD genotype was associated with a 50% decrease in Abeta(42) levels in the cerebrospinal fluid. Thus, we demonstrate a significant impact of the CTSD genotype on Abeta(42) levels in the cerebrospinal fluid of AD patients and underpin the importance of the validation of susceptibility genes by examining their potential pathophysiological relevance.

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PubMed2002

Regional N-acetylaspartate reduction in the hippocampus detected with fast proton magnetic resonance spectroscopic imaging in patients with Alzheimer disease.

OBJECTIVE: To detect regional metabolic changes that resemble the expected spatial pattern of neuronal loss in patients with Alzheimer disease (AD). METHODS: Thirty-four patients with AD and 22 healthy control subjects were included in the study. Single-slice fast proton spectroscopic imaging was performed in parallel angulation to the temporal lobes. Proton spectra were selected from the hippocampus, the lateral temporal lobe, and the occipital lobe of both hemispheres to determine metabolite concentration of N-acetylaspartate (NAA), total creatine (tCr), including phosphocreatine and creatine, and choline-containing compounds (Cho). The metabolic ratios of NAA/tCr and Cho/tCr were calculated and compared between patients with AD and healthy volunteers. RESULTS: The NAA/tCr ratios were significantly reduced in the left (F(1,1) = 4.34, P =.04) and right hippocampus (F(1,1) = 9.96, P =.003) in patients with AD. The Cho/tCr ratios remained unchanged in both hippocampi. There was no significant change of either NAA/tCr or Cho/tCr in the lateral temporal and occipital lobes of patients with AD. CONCLUSION: This study provides evidence that fast proton spectroscopic imaging may detect the regional pattern of disturbed neuronal integrity in patients with AD with high spatial resolution in a short acquisition time.

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PubMed2002

Novelty detection and repetition suppression in a passive picture viewing task: a possible approach for the evaluation of neuropsychiatric disorders.

The applicability of functional magnetic resonance imaging (fMRI) in patients with Alzheimer's disease (AD) or schizophrenia is frequently limited by cognitive impairment, which prevents the adequate execution of complex tasks. An experimental design that puts only minor demands on the patients' cognitive ability but engages disease-relevant brain structures would be of benefit. Novelty detection and repetition suppression are two basic components of memory that might be used to investigate specific brain areas under these conditions. Novelty detection has been related to hippocampal activation increases. Stimulus repetition related activation decreases (suppression) have been observed in the extrastriate cortex and have been related to perceptual priming. Both processes have been examined primarily in neuroimaging studies with complex cognitive tasks. We used event-related fMRI to investigate novelty- and repetition-related effects in an attended but passive picture-viewing task in healthy subjects. The differential activation, detected in the novel vs. repeated contrast, was located in the bilateral anterior hippocampus and in bilateral occipital and inferior-temporal areas. The hippocampal activation is of interest because medial temporal lobe lesions are key features in AD and schizophrenia. The repetition-related activation decreases in the extrastriate areas are of potential value in investigating the conflicting results regarding perceptual priming impairment in both disorders. Our results indicate that activation of disease-relevant brain regions under passive task conditions is possible. This might increase the utility of functional imaging in cognitively impaired patients.

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PubMed2002

Psychiatric disorders in relatives of subjects with Alzheimer's disease. No evidence for common genetic risk factors.

INTRODUCTION: The clustering of two or more disorders in the same family might indicate the presence of common genetic risk factors. The prevalence of various psychiatric disorders in relatives of Alzheimer's disease (AD) patients has rarely been investigated. Consequently, family study data were reinvestigated to assess, if there are indications for an overlap of genetic risk factors of AD and other psychiatric disorders. METHOD: Family history information on 2964 living and deceased first-degree relatives of 146 AD patients, 168 patients with major depression (MD) and 136 control subjects were obtained by at least one informant. Of the living relatives, 49.2 % could also be interviewed. Best-estimate lifetime diagnoses were made on all available information. Lifetime prevalences of psychiatric disorders were compared in relatives of AD patients, of MD patients and of control subjects using chi(2) statistics. Cox proportional hazards regression analyses were additionally performed to control for the relative's age, gender and source of information (interview vs. family history information). RESULTS: Relatives of AD patients had no increased risk of other psychiatric disorder compared with relatives of the comparison groups. CONCLUSION: AD is genetically distinct from other psychiatric disorders, i. e., schizophrenia, anxiety, obsessive-compulsive, somatoform disorders, alcoholism, substance abuse or dependency.

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PubMed2002

Depression in Alzheimer's disease: is there a temporal relationship between the onset of depression and the onset of dementia?

Alzheimer's disease (AD) patients often present with concurrent major depression (MD). To investigate the reasons for this comorbidity, e.g. MD being a risk factor for AD, or both diagnoses having a common neurobiology, the temporal relationship between the first onset of AD and of MD during lifetime was investigated-57 out of 146 AD patients had a lifetime diagnosis of MD. The correlation between the ages at onset of MD and dementia was calculated. The incidence of MD in AD patients in several 5-year-intervals before and after the onset of AD was compared with the average incidence of MD in the present AD sample and with the expected incidence of MD in the general population. No significant correlation between the onset of AD and of MD could be found after controlling for age, gender and the Mini-Mental-State. However, the incidence of MD 5 years before and after the onset of AD significantly exceeded the expected incidences-MD is only partially related to AD. However, the increased incidence of MD within 5 years before and after the onset of dementia may indicate that a common neurobiological process causes cognitive decline and depression in a subsample of AD patients.

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PubMed2002

Test-retest reliability of self-reported age at onset of selected psychiatric diagnoses in general health care.

OBJECTIVE: To investigate reliability of self-reported age at onset of frequent mental disorders and its association with patient and disorder characteristics. METHOD: A total of 1031 primary care patients with at least one lifetime psychiatric diagnosis were asked to report age at onset of their disorders at baseline and after 1 year. Intraclass correlation coefficients (ICC) for age at onset information were calculated for individual disorders. RESULTS: ICC were high and lay between 0.6790 (generalized anxiety disorder) and 0.7977 (dysthymia). Factors associated with reliability are different for different disorders: gender for depressive episodes, gross national product per year per inhabitant for dysthymia, age for pain disorder, years of formal education for dysthymia, generalized anxiety disorder, and agoraphobia, and number of lifetime diagnoses for depression and agoraphobia. CONCLUSION: Self-reported age at onset is reliable. Further research on factors associated with reliability should focus on interview conditions and subject parameters during interview.

Agoraphobia↗

PubMed2002

Cathepsin D: screening for new polymorphisms using single-strand conformation polymorphism analysis.

Cathepsin D (CTSD) is a lysosomal protease involved in the pathogenesis of several diseases such as breast cancer and possibly Alzheimer's disease (AD). Previous findings revealed a significant association between the T allele of the 224 C/T (A58V) polymorphism in exon 2 of the CTSD gene and late onset AD. The exonic regions of the CTSD gene were screened for further polymorphic variations using polymerase chain reaction and single-strand conformation polymorphism analysis. In addition to the known 224 C/T polymorphism and two silent mutations in exons 3 and 4 we detected two new polymorphisms in introns 5 and 8. Combination of these sequence variations results in three different haplotypes; one of these haplotypes is due to the new polymorphism in intron 5. We detected no further missense mutations except for the known 224 C/T polymorphism in exon 2. Thus, if sequence variations within the CTSD gene influence the risk for various diseases, the pathogenic mechanism is likely to be linked to the amino acid substitution in the profragment of CTSD.

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