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G Stoppe

Publications and source records attributed to G Stoppe.

At least 19 recordsLinked to original sources
PubMed2003

Association of late-onset Alzheimer disease with a genotype of PLAU, the gene encoding urokinase-type plasminogen activator on chromosome 10q22.2.

Urokinase-type plasminogen activator (uPA) converts plasminogen to plasmin. Plasmin is involved in processing of amyloid precursor protein and degrades secreted and aggregated amyloid-beta, a hallmark of Alzheimer disease (AD). PLAU, the gene encoding uPA, maps to chromosome 10q22.2 between two regions showing linkage to late-onset AD (LOAD). We genotyped a frequent C/T single nucleotide polymorphism in codon 141 of PLAU (P141L) in 347 patients with LOAD and 291 control subjects. LOAD was associated with homozygous C/C PLAU genotype in the whole sample (chi2=15.7, P=0.00039, df 2), as well as in all sub-samples stratified by gender or APOE epsilon4 carrier status (chi2> or = 6.84, P< or =0.033, df 2). Odds ratio for LOAD due to homozygosity C/C was 1.89 (95% confidence interval 1.37-2.61). PLAU is a promising new candidate gene for LOAD, with allele C (P141) being a recessive risk allele or allele T (L141) conferring protection.

Age of Onset↗
PubMed2003

[German-speaking memory clinics: state of the art and practical recommendations].

The 7th annual meeting of the memory clinics of Germany, Switzerland and Austria in March 2002 in Göttingen, Germany was an optimal opportunity to make an inventory about the state of the art in diagnostic and therapy of dementia and mild cognitive impairment in German-speaking memory clinics. Several problems were discussed including difficulties in 1) diagnosis of patients with aphasia or foreign patients, 2) handling of demented patients without a caregiver, 3) psychological support for patients, who have been diagnosed in a very early stage, 4) misunderstandings between general practitioners, neurologists and psychiatrists in private practice on the one hand and the memory clinics on the other hand, 5) recommendations for prevention of dementia, 6) recommendations concerning dementia and car driving and 7) questions of genetic counselling. The following paper is a summary of the results of a workshop in Göttingen and gives practical recommendations based on the experiences of the memory clinics.

Aged↗
PubMed2002

Critical appraisal of effects of estrogen replacement therapy on symptoms of depressed mood.

That estrogen plays a role in the regulation of mood has been postulated since extracts of animal ovarian tissue were administered to oophorectomized women at the end of the last century to alleviate psychological symptoms thought to be related to the removal of the ovaries. The occurrence of depressive symptoms in the perimenopause is associated with a variety of factors. A previous history of either depression and/or premenstrual syndrome as well as cognitive factors explain most of the variance. There are no consistent findings of a correlation between any serum hormone level and severity or presence of mood symptoms. Neurobiological studies show, with regard to an antidepressant effect, promising effects of estradiol on serotonergic, noradrenergic, cholinergic, dopaminergic and GABAergic functions. Progestogens seem to oppose some of these effects. The role of adrenergic hormones and DHEA(S) is less clear. Most clinical trials showed a modest effect on symptoms of depression. However, the predominantly poor methodological quality does not allow generalisation and recommendations. A "tonic" effect on well-being in non- or mild depressed women should not be regarded as true antidepressant effect. Results yielded in studies of surgically menopausal women may not be applicable to women with natural menopause. There is a great potential for exploring various types, doses, and routes of administration of both antidepressants and sex hormones. With regard to the domino theory, future studies should also focus on the mediation of treatment effects through alleviation of vasomotor symptoms or sleep quality.

Adult↗
PubMed2001

Non-replication of association between cathepsin D genotype and late onset Alzheimer disease.

In two recent studies from Germany, a strong association was found between the allelic variant T of the amino acid substitution encoding polymorphism 224 C/T (A38V) in exon 2 of the cathepsin D gene (CTSD) and late onset Alzheimer disease (AD). Other studies from Europe and the USA revealed ambiguous results. Therefore, we performed an independent association study on CTSD and AD in a sample of 324 Caucasian patients from Germany, Switzerland, and Italy with late onset AD, and 302 non-demented controls. We could not confirm an association between CTSD genotype and AD, although there was a slight but not significant increase in frequency of the T allele and T carrier status in AD. Post hoc data analyses suggested that there might be a stronger effect of CTSD genotype on AD risk in males, and an interaction between CTSD and APOE genotypes in males but not females.

Age Factors↗
PubMed2001

[Evolution and function of sleep].

This paper presents a brief historical review of the beginning of scientific studies on sleep research and evaluation of the electrophysiological basics. Subsequently, hypotheses are presented and discussed on phylogenesis and function of NONREM- and REM-sleep as well as aspects of the regulation of energy conservation and temperature. Sleep may have first evolved out of rest/activity cycles. Later on, with the evolution of complex brains, sleep may also assume importance in development and maintenance of these structures. Hence, special emphasis is placed on the influence of NONREM and REM sleep on the reorganisation of neuronal networks.

Animals↗
PubMed2000

Genetic association of a cystatin C gene polymorphism with late-onset Alzheimer disease.

OBJECTIVE: To determine whether the cystatin C gene (CST3) is genetically associated with late-onset Alzheimer disease (AD). DESIGN: A case-control study with 2 independent study populations of patients with AD and age-matched, cognitively normal control subjects. SETTING: The Alzheimer's Disease Research Unit at the University Hospital Hamburg-Eppendorf, Hamburg, Germany, for the initial study (n = 260). For the independent multicenter study (n = 647), an international consortium that included the Massachusetts Alzheimer's Disease Research Center at the Massachusetts General Hospital, Boston; the Scientific Institute for Research and Patient Care, Brescia, Italy; and Alzheimer's research units at the Universities of Basel and Zurich, Switzerland, and Bonn, Goettingen, and Hamburg, Germany. PARTICIPANTS: Five hundred seventeen patients with AD and 390 control subjects. MEASURES: Molecular testing of the KspI polymorphisms in the 5' flanking region and exon 1 of CST3 and the apolipoprotein E (APOE) genotype. Mini-Mental State Examination scores for both patients with AD and control subjects. RESULTS: Homozygosity for haplotype B of CST3 was significantly associated with late-onset AD in both study populations, with an odds ratio of 3.8 (95% confidence interval, 1.56-9.25) in the combined data set; heterozygosity was not associated with an increased risk. The odds ratios for CST3 B/B increased from 2.6 in those younger than 75 years to 8.8 for those aged 75 years and older. The association of CST3 B/B with AD was independent of APOE epsilon4; both genotypes independently reduced disease-free survival. CONCLUSIONS: CST3 is a susceptibility gene for late-onset AD, especially in patients aged 75 years and older. To our knowledge, CST3 B is the first autosomal recessive risk allele in late-onset AD.

Age of Onset↗
PubMed2000

Can chronic neuroleptic treatment promote sleep disturbances in elderly schizophrenic patients?

It has been proposed that sleep disturbances, especially reduced delta sleep, are related to a poor outcome in schizophrenia. To determine whether long-term treatment with neuroleptics can promote sleep disturbances by increasing the risk of a nocturnal myoclonus syndrome (NMS) (=periodic movements in sleep) related insomnia, we performed all-night polysomnography in 10 chronically ill schizophrenic patients who had been under neuroleptic therapy for a mean of 27 years. NMS-related insomnia was detected in all 10 patients. Potential pathophysiological relationships between long-term neuroleptic therapy and NMS occurrence are discussed. Our findings suggest that long-term administration of neuroleptics favours the appearance of insomnia.

Aged↗
PubMed2000

[Dementia: risk and protective factors with special consideration of gender and hormone replacement therapy].

This article focuses on the special role of women and their problems regarding the epidemiology and pathogenesis of dementia, especially Alzheimer's disease (AD). Recent epidemiological studies reveal higher rates of women affected by the two major dementing conditions, AD and vascular dementia (VaD). However, it is under debate whether a pure gender effect accounts for this, because gender differences e.g. in education, life expectancy, psychosocial development and health behaviour must be included in the analysis. Therefore it seems to be reasonable to have a look on gender related variances in other risk and protective factors of dementia. Recently, the menopause attracted the interest of dementia researchers, because retrospective studies revealed a favourable effect of hormone replacement therapy (HRT) on the incidence of AD by about 50%. However, in spite of well known "positive effects" of estrogens on the central nervous system, there is still not enough evidence for a recommendation of HRT for the prevention of AD and other dementias.

Alzheimer Disease↗
PubMed1999

Gender differences in the recognition of depression in old age.

OBJECTIVE: The study should answer the question of whether identical symptom presentations of depression in male and female patients leads to similar recognition rates in primary care. METHOD: We performed a survey in primary care. Two written case vignettes were presented to 170 family physicians in a face-to-face interview which took place in their practices. The case vignettes described either a mildly depressed otherwise healthy old patient (case 1) or a severely depressed patient with somatic comorbidity (case 2). For each case different versions with regard to patients' gender were used: in case 1 only the gender of the patient varied; in case 2 both the gender and the anamnesis (stroke/hypothyroidism) varied. Afterwards the interviewers asked standardised open questions. The physicians were not aware of the mental health focus and the gender focus of the study. RESULTS: The study is representative with a response rate of 77.6%. For primary diagnosis, the female versions were given the diagnosis of depression more often. There was a non-significant trend that female physicians considered depression more often. CONCLUSION: The results show that gender-related experience and stereotypes on the physicians' side influence the diagnosis of (old age) depression in primary care. Further studies should elucidate the influence of the physicians' gender on the management of psychiatric disorders.

Aged↗
PubMed1999

Effects of sedation, stimulation, and placebo on cerebral blood oxygenation: a magnetic resonance neuroimaging study of psychotropic drug action.

The effects of pharmacologic depression and stimulation of cerebral activity were investigated in seven healthy young volunteers using blood oxygenation-sensitive MRI at 2.0 T. Dynamic gradient-echo imaging (7 min) was performed before, during and after the intravenous application of 10 mg diazepam and 15 mg metamphetamine as well as of the corresponding drug placebos (isotonic saline) in a brain section covering frontotemporal gray matter, subcortical gray matter structures, and cerebellum. The MRI responses were significantly different for the two drugs applied (p = 0.01). Relative to signal strength during injection, metamphetamine elicited a signal increase of 0.97 +/- 0.03% (mean +/- SD, p = 0.02) within the whole section 4-5 min after injection. Similarly, both placebo conditions led to a small signal increase, i.e. 0.50 +/- 0. 03% (n.s.) for the metamphetamine placebo and 0.40 +/- 0.07% (p = 0. 03) for the diazepam placebo. Diazepam abolished this signal increase. A topographic analysis revealed the metamphetamine-induced signal increase to be more pronounced in subcortical gray matter structures (p = 0.01) and cerebellum (p = 0.02) than in frontotemporal cortical gray matter (p = 0.04). This finding is in agreement with the hypothesis that pertinent responses not only reflect global cerebral hemodynamic adjustments, but also localized perfusion changes coupled to alterations in synaptic activity. The occurrence of a placebo response is best explained by expectancy and may provide a confounding factor in the design of functional activation experiments.

Adult↗
PubMed1999

[Psychopharmacotherapy of behavioral disorders in patients with dementia].

Behavioral disorders in dementia are common and are the most important symptoms with regard to socio-economic burden. Up to now there is no common international agreement of how to define and measure these disorders. Antidementia trials focus mainly on cognition. Investigations of neurobiological corrolaries of disturbed behavior in the dementias are rare. The same holds true for studies on the longitudinal course of behavioral disorders and their interrelation. Many symptoms may be the expression of variable conditions, e.g., agitation may be related to anxiety or akathisia. In primary care, hospitals and nursing homes, antipsychotics are most often chosen for their treatment. The available data demonstrate at least a modest efficacy. New neuroleptics (risperidone, clozapine, olanzapine) offer some advantages with regard to the risk benefit ratio. Benzodiazepines are frequently prescribed, but seem to be superior to neuroleptics only for the treatment of sleep disorders. Antidepressants, carbamazepine or valproic acid offer some benefits, but do not provide immediate effects, which may the reason why they are used much less. For long-term treatment of many behavioral symptoms, they may however be superior. Drugs should also be chosen with regard to dementia etiology. For example, physicians should consider the high neuroleptic sensitivity in dementia of Lewy body type and the anticholinergic sensitivity in dementia of Alzheimer type. Empirical evidence indicates overtreatment of the demented population with sedating psychotropic drugs. With regard to the instability of behavioral disorders in the time course the necessity of drug treatment should always be (re)evaluated.

Aged↗
PubMed1999

Family physicians and the risk of suicide in the depressed elderly.

BACKGROUND: Depression is the most frequent psychiatric disorder in the elderly. It is the reason for most suicides in this age group. METHOD: We performed a representative survey in primary care. Two written case vignettes were presented to 170 family physicians in face-to-face interviews which took place in their practices. The case vignettes described either (Case 1) a mildly depressed otherwise healthy old patient or a severely depressed patient (Case 2) with somatic comorbidity. Afterwards the interviewers asked standardized open questions. The physicians were not let into the mental health focus of the study. RESULTS: The response rate was 77.6%. Depression was considered for primary or differential diagnosis by 91.2% of the physicians in Case 1 and by 70% in Case 2 (chi2-test; p < 0.01). For further anamnesis, only 2.4% of the physicians were interested in suicidal ideation of the patient. When directly asked at the end of the interview, 76.9% of the physicians said they would talk about suicide. Those who would not, thought that the patient would communicate suicidal intent himself/herself, or they feared to induce suicide by asking directly. CONCLUSION: Thinking of suicidality and its prevention is not uppermost in the physicians' mind. Therefore, and also with regard to the relatively high rate of depression recognition, we conclude that educational means should not only focus on the recognition and screening of depression, but also on the management--'how to talk about...'--of complex problems like suicide in the elderly, in order to change suicide rates.

Aged↗
PubMed1999

Behavioural problems associated with dementia: the role of newer antipsychotics.

Behavioural disorders are a common feature in dementia, especially in the later stages of the disease. The most frequent disorders are agitation, aggression, paranoid delusions, hallucinations, sleep disorders, including nocturnal wandering, incontinence and (stereotyped) vocalisations or screaming. Behavioural disorders, rather than cognitive disorders, are the main reason why caregivers place patients with dementia in a nursing home. However, although behavioural disorders are important, there is still no international agreement with respect to the description and definition of symptoms and syndromes. This also holds true for the wide variety of scales for quantification and measurement of behavioural disorders. Drug therapy should be considered after possible underlying causes such as physical illness, drug adverse effects and environmental stressors have been ruled out, or specifically addressed, and a behavioural approach has also failed. This article briefly reviews the evidence for non-antipsychotic drug therapies, which include a variety of substances. However, antipsychotics are the group of drugs which have been most frequently studied for the treatment of behavioural syndromes in dementia. Drug responsive symptoms include anxiety, verbal and physical agitation, hallucinations, delusions, uncooperativeness and hostility, whereas wandering, hoarding, unsociability, poor self-care, screaming and other stereotyped behaviour seem to be unresponsive to all drugs. Although the use of classical antipsychotics is limited by extrapyramidal symptoms, anticholinergic adverse effects, sedation and postural hypotension, the newer antipsychotics offer the chance of a better risk:benefit ratio. This article reviews the small amount of data published on the use of the newer antipsychotics, and concludes that risperidone at low dosages (0.5 to 2 mg/day) seems to be especially useful for the treatment of behavioural symptoms in dementia because of its negligible anticholinergic adverse effects. The use of clozapine is limited by its anticholinergic activity, at least in dementia of the Alzheimer and Lewy body types. However, in patients with psychosis arising from Parkinson's disease it seems to be the drug of choice, and similar activity is likely for olanzapine. There are no published data on other newer drugs, such as sertindole, quetiapine or ziprasidone. Future studies should also address questions of dementia heterogeneity and should compare different drug treatments and treatment combinations.

Antipsychotic Agents↗
PubMed1999

[Gerontopsychiatric treatment in comparison between integrated management at a university and separated management at a district hospital. 1: Patient characteristics].

OBJECTIVE: We wanted to study differences between geriatric psychiatric patients and their management in an integrated (with other adult age groups) care in the University Psychiatric Hospital (PUK) compared to those in a separated (only according to age) care in the Psychiatric State Hospital (LKH), which together treat all psychiatric inpatients in Goettingen, Germany. METHOD: We performed standardized chart reviews of randomly selected groups of patients, who had been treated in the PUK (n = 151) and the LKH (n = 145) in the years 1991 and 1992. RESULTS: The LKH patients were significantly older (74.8 +/- 8.7 y versus 70.3 +/- 8.3 y), more often living alone and/or without children. 31.9% of them were living in a nursing home compared to 6.5% of the PUK patients. Psychic disorders had not shown up before old age in 55.7% of all cases. 50.4% of the patients were in a psychiatric hospital for the first time. The majority of the patients (65.6%) had not been investigated by a psychiatrist before admission. CONCLUSIONS: More socially handicapped patients were treated in the LKH. For most cases, the hospital treatment had been the first psychiatric treatment at all.

Adult↗