Ralf Ihl

Clinical efficacy of Ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type

Among the psychiatric illnesses associated with old age primary degenerative dementia of the Alzheimer type (DAT) has gained increasing importance in recent years. Even though a curative treatment of the disease is currently impossible, various drugs can be used to slow down its progression. In the present study the influence of oral treatment with 240 mg/day of Ginkgo bilabo special extract EGb 761 (Tebonin forte, manufactured by Dr Willmar Schwabe, Karlsruhe) on the clinical course of DAT was investigated in a double-blind, randomized, placebo-controlled parallel-group design in 20 outpatients. The duration of treatment was 3 months. The primary outcome variable was the sum score in the SKT-test for the determination of attention and memory. Other psychometric tests (trailmaking test, ADAS, CGI) and electrophysiological investigations (EEG topography) were evaluated descriptively. Although the active-treatment group, with a mean sum score of 19.67 points in the, S.K.T., had a poorer baseline level than the placebo group (18.11 points), it experienced an improvement to 16.78 points under treatment with EGb 761 whereas the placebo group deteriorated to 18.89 points. The differences between the baseline and final values formed the basis for a statistical group comparison, which gave a result favourable to EGb 761, at a significance level of p < .013. In addition to this psychometric confirmation of efficacy, certain descriptive trends were found at the psychopathological (Clinical Global Impression) and dynamic functional (EEG findings) levels, which can be interpreted as evidence of effectiveness of Ginkgo biloba special extract EGb 761 in mild to moderate dementia and of local effects in the central nervous system. Inter-group differences in the ADAS cognitive and non-cognitive subscales did not reach statistical significance, probably because of the small sample size.

Differential Validity of Psychometric Tests in Dementia of the Alzheimer Type

Forty-nine patients with a clinical diagnosis of probable dementia of the Alzheimer type underwent an extensive test battery designed to evaluate cognitive deficits according to NINCDS/ADRDA criteria. All patients demonstrated signs of impairment on this test battery. One day later, they were administered a second test battery that consisted of the Mini-Mental State Examination (MMS), the Alzheimers Disease Assessment Scale (ADAS), the SKT test (SKT), and the Brief Cognitive Rating Scale (BCRS) to assess the construct validity, sensitivity, and possible shortcomings of these tests. A control group of 47 age-matched persons was administered the same test battery to allow a comparison with reference values from other studies. Due to the design of the study, values of controls and patients did not overlap. Intercorrelations in patients were above 0.65 (p < 0.05 after Bonferroni correction) for all four cognitive tests. The ADAS and BCRS appeared to document the whole course of the disease in patients studied. The best differentiation with the SKT test could be obtained in mild to moderate dementia; however, due to the tests construction, a floor effect demonstrated its limitations in the case of severe dementia. Results obtained with the MMSE indicated the contrary: a ceiling effect showed its lack of differentiation in mild dementia. Therefore, a combination of tests should be used in the evaluation of cognitive deficits in the course of dementia of the Alzheimer type.

Alzheimer's Disease Assessment Scale: Reliability and Validity in a Multicenter Clinical Trial

Psychometric characteristics of the Alzheimers Disease Assessment Scale (ADAS) were examined on the basis of data from 440 patients with dementia of the Alzheimer type that were collected before treatment in a multicenter clinical drug trial. Coefficients of internal consistency of above .80 for the cognitive (ADAS-Cog) and the noncognitive section (ADAS-Noncog) indicated a high degree of homogeneity of item contents within the two assessment domains. Test-retest reliability was estimated to be .93, .98, and .96 for ADAS-Cog, ADAS-Noncog, and the total score (ADAS-Total), respectively. Reliably detectable individual changes, which were derived from the reliability estimates, were 7, 3, and 8 points for ADAS-Cog, ADAS-Noncog, and ADAS-Total, in that order. Factor analysis and correlations with MMSE, SKT, and NOSGER scores support the validity of the ADAS-Cog and ADAS-Noncog scores with regard to the cognitive and the noncognitive assessment domains. The ADAS summary scores, almost all of the cognitive items, and some of the noncognitive items discriminated significantly between stages of severity of dementia, as classified independently by MMSE and SKT scores.

Electrophysiological correlates of emotional and structural face processing in humans.

In order to study brain potentials related to decoding of facial expressions of emotions and those, related to basic perception of faces 16 right-handed subjects performed tasks on facial emotion recognition and perception of blurred faces and objects. Electroencephalograph (EEG) recordings during performance of the tasks revealed similar event-related potentials during the presentation of faces at 120 and 170 ms after stimulus onset in both of the tasks but significant differences in amplitudes between 180 and 300 ms. Whereas faces in the emotion recognition task produced high amplitudes in that latency range, potentials in response to faces in the blurred object condition were virtually absent. These data point to the assumption that decoding of facial expressions starts early in the brain and might be processed separately from basic stages of face perception.

EEG-correlates of facial affect recognition and categorisation of blurred faces in schizophrenic patients and healthy volunteers

The ability to recognise emotional expressions of faces and the ability to categorise blurred and non-blurred faces and complex objects was tested in 16 schizophrenic in-patients and 16 healthy volunteers. EEGs were recorded during performance of the tasks and event-related potentials were compared between groups. Patients performed worse than healthy volunteers in recognition of facial affect but not in categorisation of blurred faces. Furthermore, within a 180-250ms latency range patients showed reduced amplitudes during affect recognition compared with controls but not during categorisation of blurred faces. Amplitudes recorded at frontal electrode sites were associated with performance in facial affect recognition. These results provide a first clue to the neurophysiological basis of the widely reported facial affect recognition deficit in schizophrenic patients.

Efficacy and safety of a once-daily formulation of Ginkgo biloba extract EGb 761 in dementia with neuropsychiatric features: a randomized controlled trial

To test the efficacy and safety of a once‐daily formulation of EGb 761 in the treatment of patients with dementia with neuropsychiatric features.

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Alzheimer's disease and other dementias

Abstract Objectives. To define a practice guideline for biological treatment of dementia and to make transparent the development of the guideline connecting the original data with the resulting recommendations. Methods. This guideline includes pharmacologic treatment considerations for patients with Alzheimers disease, vascular dementia, DLB, and fronto-temporal dementia. Studies were selected that represent double-blind placebo-controlled trials of at least 3 months duration in patients with a diagnosis of dementia according to accepted international diagnostic criteria (for example the NINCDS/ADRDA or NINDS/AIREN criteria). Moreover, to be included studies had to fulfill a restrictive set of methodological criteria. Original studies and not meta-analyses determined the evaluation and the development of recommendations. Results. Antidementia pharmaceuticals neither cure nor arrest the disease. A modest effect of improvement of symptoms compared with placebo can be observed. Antidementia pharmaceuticals show different efficacy and side effect profiles. The type of dementia, the individual symptom constellation and the tolerability should determine what medication should be used. There are hints that combination therapy of drugs with different therapeutic mechanisms might improve the efficacy. In treating neuropsychiatric symptoms (NPS), psychosocial intervention should be the treatment of first choice. Pharmaceuticals can only be recommended when psychosocial interventions is not adequate. However, even then the side effects of pharmaceuticals limit their use. Conclusions. Depending on the diagnostic entity and the pathology treated different anti-dementia drugs can be recommended to improve symptoms. In the management of NPS, side effects limit the use of medications even when psychosocial interventions have failed. Thus, there is an urgent need to develop more efficacious medications for the treatment of dementia.

Quantitative EEG in progressing vs stable mild cognitive impairment (MCI): results of a 1-year follow-up study

The study objective is to evaluate the use of qEEG data for the cross‐sectional differentiation of mild cognitive impairment (MCI) from mild Alzheimers disease (AD) and in the longitudinal prediction of cognitive decline in MCI.

Treatment effects of Memantine on language in moderate to severe Alzheimer's disease patients.

Language impairment is one of the most troublesome manifestations of Alzheimers disease (AD). The objective of this post hoc analysis was to assess the treatment effects of Memantine on language in patients with moderate to severe AD, using the recently developed Severe Impairment Battery‐Language (SIB‐L) scale.

Odor identification in Alzheimer’s disease and depression

Background and aims: In Alzheimer’s disease (AD) olfactory deficits are common and depression is a difficult differential diagnosis. We therefore investigated the usefulness of an odor identification test to differentiate both conditions. Methods: Twenty patients with probable Alzheimer’s disease (AD), twenty elderly patients with a depressive disorder, and thirty healthy elderly subjects performed a German odor identification test. Results: AD patients had significantly lower odor identification scores, compared with both depressive patients and control subjects (F=121.96, df=2, 67, p<0.001). With a cut-off score of 10/11, the sensitivity of the identification test to differentiate AD patients from depressive patients was 100%, and specificity was 95%. Conclusions: The odor identification test used in this study is able to reveal olfactory deficits in AD. It also seems to be a useful instrument to differentiate AD from depression.