[The "Lector"--a testing method to determine verbal educational level]. / Der "Lector"--ein Untersuchungsverfahren zur Bestimmung des verbalen Bildungsniveaus.

Assessment of the educational level is important to prevent false neuropsychological diagnostic decisions. In the German-speaking countries some instruments for this assessment already exist, but there are problems involved in the practical application. There still is no reading test, which is a common standard in international neuropsychological test batteries. The lector investigates how subjects read rare German words or foreign words used in German-speaking countries. Words were selected which are pronounced differently from German pronunciation rules. A subject who does not know the word will pronounce it false, i.e., according to the German pronunciation rule. Norms (percentiles), estimation of reliability, and first data about validity were calculated from three samples with a total of 503 subjects. On the basis of the data presented, the Lector Test can be used as a control variable in research with groups as well as in neuropsychological diagnostics.

[Mental competence and neuropsychologic impairments in demented patients]. / Einwilligungsfähigkeit und neuropsychologische Einschränkungen bei dementen Patienten.

The study aim was to examine if neuropsychological tests and clinical dementia scales identify incompetent patients with dementia. Eighteen demented outpatients (ICD-10: F00-F03) underwent psychiatric examination, neuropsychological testing, and formal (MacArthur Competence Assessment Tool Treatment, Hopkins Competency Assessment Test) and clinical assessment of competence. Clinical dementia scales but not neuropsychological testing correlate with formal and clinical assessment of competence in patients with dementia. Our results do not support a neuropsychological model of competence assessment. However, in cases with poor results in clinical dementia scales, clinicians should assess the patients' competence in more detail. It remains open which is the best and ethically grounded methodology for competence assessment.

Safety and efficacy of idebenone versus tacrine in patients with Alzheimer's disease: results of a randomized, double-blind, parallel-group multicenter study.

This study evaluated the safety and efficacy of idebenone vs. tacrine in a prospective, randomized, double-blind, parallel-group multicenter study in patients suffering from dementia of the Alzheimer type (DAT) of mild to moderate degree. Diagnosis was based on DSM-III-R (primary degenerative dementia) and NINCDS-ADRDA criteria (probable Alzheimer's disease). A total of 203 patients of both sexes aged between 40 and 90 years were randomized to either idebenone 360 mg/day (n = 104) or tacrine up to 160 mg/day (n = 99) and treated for 60 weeks. The primary outcome measure was the Efficacy Index Score (EIS). The EIS combines dropout as well as the relevant improvements individually across the three levels of assessment (cognitive function, activities of daily living, global function). Secondary outcome measures were the ADAS-Cog score, the NOSGER-IADL score and the clinical global response (CGI-Improvement). After 60 weeks of treatment, 28.8 % of the patients randomized to idebenone, but only 9.1 % of the patients randomized to tacrine were still on the drug. In the LOCF analysis, 50 % of the patients randomized to idebenone but only 39.4 % of the patients randomized to tacrine showed an improvement in the Efficacy Index Score or at least one of the secondary outcome variables. The primary efficacy measurement was the change of the Efficacy Index Score from baseline to the assessment after 60 weeks treatment. The analysis was done on intention-to-treat (ITT) in a before-and-after test design. Patients randomized to idebenone showed a higher benefit from treatment than patients randomized to tacrine. We conclude that the benefit-risk ratio is favorable for idebenone compared to tacrine, and furthermore, that this ratio is likely to be similar when comparing idebenone to other cholinesterase inhibitors.

Multicenter field trial on possible health effects of toluene. II. Cross-sectional evaluation of acute low-level exposure.

Data on possible acute effects of today's relevant low-level exposure to toluene are contradictory, and information on possible effects of exposure under occupational conditions is largely lacking. In a controlled, multi-center, blinded field trial, effects possibly associated with acute toluene exposure were evaluated in workers of 12 German rotogravure factories. Medical examinations (inquiries on subjective symptoms, and standard tests of psycho-physiological and psycho-motor functions) were performed on almost 1500 volunteers, of whom 1290 were toluene-exposed (1178 men and 112 women), and about 200 participants served as references (157 men and 37 women), but the main aim of the trial was to reveal dose-response relationships. All volunteers were of the morning work-shift (6 h exposure). Both individual ambient air concentrations (time-weighted average) during the work-shift, as well as blood toluene concentrations after the work-shift were measured. Therefore, the medical data could for the first time be correlated with the actual individual body burden (blood toluene level) at the time of testing. In order to largely exclude confounding by chronic toluene exposure, kinetic measurements as well as the psycho-physiological and psycho-motoric tests were performed before and after the work-shift. Except for minor statistical deviations, neither convincing dose-dependent acute effects could be demonstrated with regression analyses in male volunteers at the exposure levels evaluated, nor were significant differences found when applying group statistics (highly toluene-exposed group versus volunteers with negligible exposure). Due to the rather large number of participants, the predictive power of the study is high, especially when compared with previous publications. In two psycho-physiological tests, a few more female volunteers with quite low toluene body burdens (<340 microg/l blood) showed relatively low scores when compared with participants of the reference group. Although evidence for a medical relevance is meager, the small numbers of participants, in both the exposure and the reference groups, hamper a reliable interpretation of the results concerning exposure levels above 85 microg toluene/l blood, and it is difficult to take confounding factors adequately into account. For the end points evaluated and under occupational conditions, neither blood toluene levels of 850 to 1700 microg/l (in the highest exposure group [EXPO-IV] with 56 participants), as measured 1/2 (+/-1/2) h after the work-shift, nor ambient air concentrations (time-weighted average over 6 h) between 50 and 100 ppm (188-375 mg/m(3)) were convincingly associated with alterations in psycho-physiological and psycho-motoric performances or increased the frequency of subjective complaints in male volunteers. For higher dose ranges of toluene exposure (i.e. >1700 microg toluene/l blood [or >100 ppm in ambient air]), our data set is too small for far reaching conclusions. Our data are insufficient for conclusions on a possibly higher susceptibility to toluene of some female workers. Results of kinetic studies and possible effects of long-term exposure are discussed in two accompanying publications (Neubert et al., 2001; Gericke et al., 2001).

Multicenter field trial on possible health effects of toluene. III. Evaluation of effects after long-term exposure.

In rotogravure industry, contributing considerably to mass color printing of catalogues and magazines, toluene is still extensively used as paint solvent, and many printers have been exposed to this chemical for several decades. Information on adverse health effects associated with long-term toluene exposure is still controversial. In a multi-center study, adverse health effects possibly associated with long-term toluene exposure were evaluated. In 12 rotogravure factories, 1226 male volunteers were recruited, and sufficient information on exposure and on medical data was compiled for about 1077 of them. Evaluations included: physical examination, standard tests of psycho-physiological and psycho-motoric performances, self-report of subjective symptoms, and data on a variety of laboratory blood tests. The medical data were correlated with the length (months) of toluene exposure, and a rough estimate of the extent of exposure (i.e. highly exposed printers and their helpers versus employees working at locations with low or negligible toluene exposure). A small reference group (n=109) was selected from companies of the paper industry. When linear regression curves were calculated (test results versus duration of exposure), extremely low overall coefficients of determination (r(2) adj.) of a few percent were estimated within the data clouds, with sometimes statistically significant P-values. Closer analyses revealed a strong influence of the confounding factor age, no clustering of abnormal values of highly toluene-exposed volunteers, and the vast majority or all values of the highly and long-term toluene-exposed participants staying within the reference ranges. Thus, no medical relevance of P-values <0.05 could be recognized in this evaluation, and there may have been some border-line deviations or results largely occurring by chance in the large trial. In a small cluster of the many rotogravure printers toluene-exposed for more than 20 years, the highest systolic blood pressure values of the study were found, but many possible confounding factors were not taken into account. Data on acute exposure and possible effects are presented in accompanying papers (Neubert et al., 2001a, Neubert et al., 2001b). Restricting the conclusions to the end points evaluated as well as the apparent limitations of the evaluation, no evidence was found that long-term occupational toluene exposure extending over several decades in the rotogravure industry in the Western part of Germany was convincingly associated with chronic adverse health effects or convincingly altered surrogate markers in still working male volunteers. Several peculiarities and pitfalls arising when interpreting medical data associated with such a type of environmental exposure must be considered. Reversibility of alterations previously induced at higher levels of toluene-exposure, as well as a healthy workers effect, cannot be excluded for some of the medical end points evaluated.

Spontaneous speech of patients with dementia of the Alzheimer type and mild cognitive impairment.

This article discusses the potential of three assessments of language function in the diagnosis of Alzheimer-type dementia (DAT). A total of 115 patients (mean age 65.9 years) attending a memory clinic were assessed using three language tests: a picture description task (Boston Cookie-Theft picture), the Boston Naming Test, and a semantic and phonemic word fluency measure. Results of these assessments were compared with those of clinical diagnosis including the Global Deterioration Scale (GDS). The patients were classified by ICD-10 diagnosis and GDS stage as without cognitive impairment (n = 40), mild cognitive impairment (n = 34), mild DAT (n = 21), and moderate to severe DAT (n = 20). Hypotheses were (a) that the complex task of a picture description could more readily identify language disturbances than specific language tests and that (b) examination of spontaneous speech could help to identify patients with even mild forms of DAT. In the picture description task, all diagnostic groups produced an equal number of words. However, patients with mild or moderate to severe DAT described significantly fewer objects and persons, actions, features, and localizations than patients without or with mild cognitive impairment. Persons with mild cognitive impairment had results similar to those without cognitive impairment. The Boston Naming Test and both fluency measures were superior to the picture description task in differentiating the diagnostic groups. In sum, both hypotheses had to be rejected. Our results confirm that DAT patients have distinct semantic speech disturbances whereas they are not impaired in the amount of produced speech.

Amantadine revisited: an open trial of amantadinesulfate treatment in chronically depressed patients with Borna disease virus infection.

Amantadinesulfate is a well known substance which has proven useful in the treatment and prophylaxis of viral infections, in treating symptoms of Parkinson's disease, cocaine dependence, and apathy in multiple sclerosis. It has also been reported as having mild antidepressive effects not sufficient to warrant its use as an antidepressant. Striking antidepressive effects in some patients have been attributed to its antiviral activity against human Borna disease virus (BDV) infection which is frequently seen in patients with depressive episodes. In this 8 to 12 week open study of oral amantadine in 30 depressed patients with various states of BDV infection we found a significant antidepressive response in 19 of 30. Peripheral BDV antigen indicating acute infection was cleared in both responders and non-responders, but only in responders peripheral infection was significantly reduced.

Neural correlates of recognition memory with and without recollection in patients with Alzheimer's disease and healthy controls.

To dissociate recognition memory with and without recollection, event-related potentials (ERPs) of patients with Alzheimer's disease (AD) and matched controls were recorded in a test of verbal recognition memory accompanied by a source judgement. AD patients who had smaller hippocampi showed a disability to recollect the study context (source). Their ERPs elicited by correctly recognized old words compared to new items were more positive only between 300 and 500 ms with a maximum over the frontal scalp. Controls exhibited a sustained old/new effect over left temporoparietal and frontal sites. The present findings suggest that preserved recognition memory in patients with mild AD is independent of hippocampally mediated processes recollecting episodic memories.

Measuring the efficacy of psychopharmacological treatment of psychomotoric restlessness in dementia: clinical evaluation of tiapride.

A major problem in psychogeriatrics is the treatment of demented patients suffering from severe restlessness and aggressive behavior. There have been few controlled studies of the efficacy of antipsychotic drugs in the treatment of this condition. Therefore, a multi-centre, double-blind, randomized study, measuring the efficacy and safety of tiapride vs. melperone in hospitalized dementia patients suffering from psychomotoric agitation, was conducted in 24 psychiatric hospitals in Germany. A total of 176 patients were enrolled: 175 of them were included in the safety analysis and 156 were evaluated for efficacy. Both treatment groups were comparable regarding the severity of disease and demographic data as well as with regard to the neuropsychological baseline assessment. The CGI (item, 2) was the primary efficacy parameter. Both groups yielded an identical response rate of 74.36%. The secondary efficacy parameters (NOSIE, AIMS, RAPSU, BePU, VAS) showed correspondingly a marked improvement for both groups. No significant changes of the safety parameters (blood pressure, pulse rate, ECG, clinical examination) occurred in the study. The overall number of adverse events was slightly higher in the tiapride group, serious events occurring less frequently. This study demonstrates that tiapride is as effective and as safe as melperone. These results are consistent with international experience on tiapride.

Potential of cognitive plasticity as a diagnostic instrument: a cross-validation and extension.

Examination of the range and limits of cognitive developmental reserve capacity (plasticity) by means of cognitive training has been proffered as a promising diagnostic strategy for the early identification of Alzheimer's disease. Previous findings of differential gains after cognitive training for healthy older persons and older persons at risk for dementia were supported, rendering cognitive plasticity a criterion by which the overlap in performance distributions between healthy older persons and older persons at risk can be reduced. Stepwise hierarchical regression analyses demonstrated that posttraining scores, which represented developmental reserve capacity, explained significantly more variance in mental health status than pretest or baseline performance. Older persons at risk profited significantly less from training in 2 components of fluid intelligence, figural relations, and inductive reasoning. The authors discuss the possibilities of turning this testing-the-limits procedure into an instrument for screening purposes in clinical practice.

Testing for limits of cognitive reserve capacity: a promising strategy for early diagnosis of dementia?

Examination of the range and limits of cognitive reserve capacity (plasticity) by means of cognitive training is proffered as a promising diagnostic strategy for the early (premorbid) identification of dementia, particularly Alzheimer's disease, in nonclinical populations. First data are presented from a sample of elderly independent-living people classified as healthy or at risk (beginning dementia) on the basis of a standardized psychiatric interview. Randomly assigned groups participated in a cognitive training program based on figural relations, a component of fluid intelligence. Stepwise regression analyses demonstrated that only healthy elderly profited from training and that only post-training scores predicted the psychiatric "at risk" diagnosis. The results hold promise for further development of testing-the-limits of individual differences in cognitive reserve capacity to identify premorbid states of dementia in nonclinical samples.

Emotion control and cerebellar atrophy in senile dementia.

New research increasingly indicates that the cerebellum coordinates and integrates a wide range of processes not confined to the motor sphere. Since satisfying correlations between affective disturbances and signs of cerebral atrophy have not been found, the relationship of CT-indicated cerebellar atrophy to certain psychopathologic indicators, in patients suffering from senile dementia, has been studied. The patients participating in the study were 21 women and 18 men with a mean age of 69.4 years. Each patient showed a definite pathologic score in at least one cerebral CT-measurement. The Spearman rank correlations between affective incontinency, lability of affect, and cerebellar atrophy suggest substantial relationships between affective symptoms and cerebellar pathology. This seems all the more remarkable since all of the various indicators of cerebral cortical and subcortical atrophy lacked to show any strong relationship to affective symptoms at all. The implications of the findings for research and clinical purposes are discussed.

[Non-medicinal treatment in psychogeriatrics (author's transl)]. / Nicht-medikamentöse Behandlung in der Gerontopsychiatrie.

Of the triad of possible concepts of psychogeriatric therapy which includes pharmacotherapy, psychotherapy and social therapy, the non-medicinal treatment of the elderly is dealt with here, starting from the experience of our own team in the outpatient and part inpatient sphere and in the interdisciplinary team. For psychotherapy in its strict sense, approaches are described which arise from the elaboration of deep psychology, learning theory or client-centered therapy. Forms of treatment are described and possibilities for concrete aids in the patients' environment outlined.

[Concepts of medicinal treatment in psychogeriatrics (author's transl)]. / Medikamentöse Behandlung in der Gerontopsychiatrie.

Of the triad of possible concepts of psychogeriatric therapy which includes pharmacotherapy, psychotherapy and social therapy, the use of drugs in older people is dealt with primarily here, starting from the experience of our own work in the outpatient and part inpatient sphere and in the interdisciplinary team. In addition the literature relevant to the theme is also referred to. Characteristic peculiarities which are to be taken into consideration in drug treatment of old people are outlined. The groups of preparations important for therapy of psychological states are discussed with reference to indication and side-effects.