Erbliche Ursachen und Risikofaktoren der Alzheimer-Krankheit

A multifactorial etiology underlies the majority of cases of Alzheimer's disease (AD). Both ill-defined environmental and genetic factors contribute to the development of the disease. Allele epsilon 4 of ApoE is a genetic risk factor. Its presence increases the risk of developing AD. However, presence of e4 is neither necessary nor sufficient for the disease to arise. Apart from the common multifactorial forms of the disease, there are rare variants which are inherited as Mendelian traits. To date three genes are known that can be mutated in these rare forms of AD. Of these, mutations in the gene presenilin 1 on chromosome 14 are most frequent. In addition, mutations in the gene presenilin 2 on chromosome 1 and in the amyloid precursor protein gene (APP on chromosome 21) occur in autosomal dominant AD. This article reviews our present knowledge of the genetics of AD and discusses its relevance for patients with AD and their relatives.     

Brain activation during dichotic presentations of consonant-vowel and musical instrument stimuli: a 15O-PET study

Dichotic listening means that two different stimuli are presented at the same time, one in each ear. This technique is frequently used in experimental and clinical studies as a measure of hemispheric specialization. The primary aim of the present study was to record regional changes in the distribution of cerebral blood flow (CBF) with the 15O-PET technique to dichotically presented consonant-vowel (CV) and musical instrument stimuli, in order to test the basic assumption of differential hemispheric involvement when stimuli presented to one ear dominate over stimuli presented in the other ear. All stimuli were 380 ms in duration with a 1000 ms interstimulus interval, and were presented in blocks of either CV-syllable or musical instrument pairs. Twelve normal healthy subjects had to press a button whenever they detected a CV-syllable or a musical instrument target in a stream of CV- and musical instrument distractor stimuli. The targets appeared equally often in the right and left ear channel. The CV-syllable and musical instrument targets activated bilateral areas in the superior temporal gyri. However, there were significant interactions with regard to asymmetry of the magnitude of peak activation in the significant activation clusters. The CV-syllables resulted in greater neural activation in the left temporal lobe while the musical instruments resulted in greater neural activation in the right temporal lobe. Within-subjects correlations between magnitude of dichotic listening and CBF asymmetry were, however, non-significant. The changes in neural activation were closely mimicked by the performance data which showed a right ear superiority in response accuracy for the CV-syllables, and a left ear superiority for the musical instruments. In addition to the temporal lobe activations, there were activation tendencies in the left inferior frontal lobe, right dorsolateral prefrontal cortex, left occipital lobe, and cerebellum.     

Pramipexole, a nonergot dopamine agonist, is effective against rest tremor in intermediate to advanced Parkinson's disease.

We evaluated the efficacy of the nonergot dopamine receptor agonist pramipexole in 16 patients with advanced Parkinson's disease and marked rest tremor during an "on" period. The patients were drawn from a larger placebo-controlled, double-blind, randomized trial, which was not originally designed to investigate the effect of pramipexole on tremor. Eleven patients received pramipexole. The first effects were seen with a pramipexole dose of 0.75 mg/d with a reduction of the tremor item A of Unified Parkinson's Disease Rating Scale (UPDRS III, "on" state) by 25% and of rigidity and akinesia by 22%. Under the highest dose, 4.5 mg/d, the tremor score was improved by 61% over baseline (p < 0.0056, Wilcoxon signed rank) and the sum of rigidity and akinesia items by 66% (p < 0.0038, Wilcoxon signed rank). Five patients received placebo and did not improve. Based on this sample of patients, the nonergot dopamine receptor agonist pramipexole appears to have a potent anti-rest tremor action while being effective against akinesia and rigidity.     

Internally and externally guided voluntary saccades in unmedicated and medicated schizophrenic patients. Part I. Saccadic velocity

Saccadic eye movements were elicited in 30 schizophrenic patients before and in 17 of these 30 during antipsychotic treatment with neuroleptics, and compared with those of 12 age-matched controls under three different conditions: (a) the gap paradigm, which tests the visually triggered and visually guided saccades; (b) the anti-task paradigm, which tests the internally guided, visually triggered saccades; and (c) the memory paradigm, which tests the internally triggered and guided saccades. Eye movements were recorded by DC electro-oculography, and the peak eye velocities for the different saccades were calculated. We found that antipsychotic treatment with neuroleptics reduces the peak saccadic eye velocity. This effect is larger for internally guided saccades than for externally triggered and guided eye movements. The saccadic velocity of the unmedicated schizophrenic patients did not differ from that of the controls. Since patients with diseases of the basal ganglia primarily show abnormalities of the internally guided and triggered saccades, our findings indicate that neuroleptics influence the oculomotor loop through the basal ganglia and that this loop, by means of neuroleptic influence on the brainstem saccadic burst generator, also influences the peak velocity of the internally guided saccades. This contradicts the current idea of the role of the cortical input to the brainstem saccadic burst generator, which is thought to not be involved in the determination of saccadic velocity. Received: 20 December 1997 / Accepted: 15 September 1998     

Prevalence, incidence and age at onset of psychiatric disorders in Norway

  Background: Increased demands for psychiatric services and increased rates of sickness absence for depression have raised the question of the occurrence of psychiatric disorders in Norway, and whether there is in fact a rising incidence rate. Methods: Between 1989–1991, 2015 and 617 persons participated in a two-phase population study. Phase I comprised screening by the Hopkins Symptom Check List 25 items (HSCL-25), and phase II a diagnostic interview by the Composite International Diagnostic Interview (CIDI), including report of date (year) of the first occurrence of any symptoms, and any consequent diagnosis: Results: A symptom score of 1.75 or more was found in 19.8% of the women and 9.3% of the men by the HSCL-25. Depression, anxiety or somatoform disorder by CIDI was found in 21.5% of the women and 11.5% of the men. The incidence rate increased significantly from 3.3 to 12.8 per 1000 person years from 1930 to 1991. The incidence rate in the year before the interview was 42.6 per 1000 person years. Age of onset became lower. More women became ill, but the illness seemed to last longer in men. A major problem in comparing results between studies is the different concepts and operationalisations of psychiatric illness, and the varying time periods given for estimates. Conclusion: The findings provide evidence of psychiatric illness being a rising and major health problem, but the role of recall bias must be further investigated. Accepted: 19 August 1999     

GCH1 mutation in a patient with adult-onset oromandibular dystonia

The authors report a mutation in exon 5 of GCH1 in a patient with adult-onset oromandibular dystonia and no obvious family history of dystonia. The patient responded positively to treatment with L-dopa. These findings demonstrate that GCH1 mutations must be considered even in patients with dystonic symptoms not typical of dopa-responsive dystonia.     

A psychiatric 12-year follow-up of adult patients with neurofibromatosis type 1

The impact of neurofibromatosis type 1 (NF1) on psychiatric symptoms and diagnoses, personality variables and self evaluation was studied in a 12 year-follow-up of patients with NF 1 in the city of G?teborg, Sweden. 48 living adult patients with NF1 were re-evaluated in 1990 in a 12 year long time follow up study. The patients were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders. The following scales were used; the Comprehensive Psychopathological Rating Scale (CPRS), the Karolinska Scales of Personality inventory (KSP) and the Self-Evaluation Scale (SES). A significant psychopathology was found in the NFI patients, p <0.001. One third of the patients were affected by a psychiatric disease, 21% by dysthymia. There was no significant progress in psychiatric symptoms in the follow up period. The personality profile disclosed a heightened self-esteem. The chronic stigmatizing character of NF1 may be the reason for the increased psychopathology found.     

Screening for somatization and hypochondriasis in primary care and neurological in-patients: a seven-item scale for hypochondriasis and somatization

The aim of this study was to investigate the internal and external validity of the Whiteley Index as a screening instrument for somatization illness. A 14-item version of the Whiteley Index for hypochondriacal traits was given to 99 of 191 consecutive primary care patients, aged 18-65 years, and to 100 consecutive patients, aged 18-60 years, admitted for the first time to a neurological ward. The primary care sample was, in addition, interviewed by means of the SCAN (Schedules for Clinical Assessment in Neuropsychiatry) psychiatric interview. The GPs and the neurologists were asked to rate various characteristics of the patients that might indicate somatization. The internal validity of the Whiteley Index was tested by means of latent structure analysis. On this basis, a reduced seven-item scale (Whiteley-7 scale) and two subscales (i.e., an Illness Conviction and Illness Worrying scale, each with three items) were constructed. All three had a high internal validity fitting into the very restricted Rasch statistical model (p>0.05) and an acceptable transferability between most of the subpopulations investigated. In the primary care population, the Whiteley-7 and the Illness Conviction scales at cut-point 0/1 showed 1.00 and 0.87 sensitivity and 0.65 and 0.87 specificity, respectively, using as "gold standard" the fulfillment of criteria for at least one ICD-10 somatoform disorder, and 0.71 and 0.63 sensitivity and 0.62 and 0.87 specificity, respectively, as gold standard for the fulfillment of criteria for at least one DSM-IV somatoform disorder, excluding the NOS diagnostic group. The Illness Worrying subscale showed less impressive performance in this respect. The agreement between the Whiteley-7 scale including the two subscales and neurologists' rating and the GPs' rating and the somatization subscale on the SCL-90 was modest or worse. It may be concluded that the Whiteley-7 scale and the Illness Conviction subscale had acceptable psychometric profiles, and both seem to be promising screening tools for not only hypochondriasis but also for somatoform disorders in general.     

Tremor frequency patterns in mercury vapor exposure, compared with early Parkinson's disease and essential tremor

A new portable tremometer allows determination of tremor intensities at different tremor frequencies. Based on past studies, two tremor frequency windows of similar size were chosen at 3.0-6.5 Hz and 6.6-10.0 Hz to reflect major tremor intensities in Parkinson's disease and mercury vapor poisoning, respectively. In 81 healthy controls, total tremor intensity was higher for the preferred hand and depended on age. Ten patients treated for Parkinson's disease showed substantially increased tremor intensity, especially within the low-frequency window. This pattern was also apparent in 14 patients with de novo Parkinson's disease whose overall tremor intensity was only mildly elevated. In contrast, ten patients with essential tremor had peak frequencies in both windows, and some patients had increased tremor on one side only. Sixty-three Brazilian gold traders exposed to mercury vapor showed increased tremor predominantly in the high-frequency window. Three of the gold traders had a narrower tremor peak at frequencies of 7-8 Hz. While the urine-mercury concentration was significantly associated with the current number of burning sessions per week, it did not correlate with tremor intensities. However, eight traders had a urinary mercury excretion level above 50 microg and at the same time a greatly increased average tremor intensity within the high-frequency window. These patterns were statistically significant for relative tremor intensities, but were less clear when total intensities were used. These observations suggest that the relative distribution of tremor intensities in specific frequency bands may be a valuable supplement to current diagnostic methods for subjects with mercury vapor exposure.     

Repetitive transcranial magnetic stimulation (rTMS) in pharmacotherapy-refractory major depression: comparative study of fast, slow and sham rTMS

In previous studies, fast repetitive transcranial magnetic stimulation (rTMS) with a frequency > 1 Hz demonstrated substantial antidepressant effects compared to sham rTMS. However, it is not clear whether fast rTMS is superior to slow rTMS (frequency < or = 1 Hz) which is safe at therapeutically promising higher intensities. The aim of this double-blind study was to compare the action of fast, slow and sham rTMS. Eighteen patients with pharmacotherapy-resistant major depression were randomized to receive fast (10 Hz), slow (0.3 Hz) or sham rTMS with 250 stimuli/day for 5 successive days. rTMS was applied at 90% motor threshold intensity to the left dorsolateral prefrontal cortex. Scores on the Hamilton Depression Rating Scale (HDRS), but not on the Montgomery-Asberg Depression Rating Scale (MADRS), showed a statistically significant time x group interaction with a reduction of 19% after slow rTMS. However, the effect was clinically marginal and not reflected by self-rating scores. Verbal memory and reaction performance were not impaired after rTMS, and there was even a statistically significant time x group interaction with improvement of verbal memory performance after fast rTMS. In conclusion, this study further supported the safety of rTMS but does not show any clinically meaningful antidepressant efficacy of rTMS at 250 daily stimuli over 5 days in pharmacotherapy-refractory major depression.