Therapeutic efficacy of vincamine in dementia.

This trial was performed to investigate the therapeutic efficacy of vincamine in the treatment of primary degenerative and vascular dementia. 152 male and female patients aged between 50 and 85 years from two psychogeriatric centers and two nursing homes were initially included in the trial and screened for eligibility. 142 patients completed the trial. Clinical diagnosis was established according to DSM-III-R criteria. Allocation of the patients to the primary degenerative dementia of the Alzheimer type (DAT) group or the multi-infarct dementia (MID) group was based on computed tomography scans, electroencephalographic findings and the Hachinski Ischemic Score. In a 12-week double-blind treatment either 30 mg vincamine or placebo was given twice daily. Confirmatory statistics included item 2 of the Clinical Global Impression (CGI), the total score of the Sandoz Clinical Assessment Geriatric (SCAG) scale, the subscale 'need for help' of the nurse's rating of geriatric patients (Beurteilungsskala für geriatrische Patienten; BGP) and the total score of the Short Cognitive Performance Test (Syndrom-Kurztest; SKT). In addition, data on tolerance and on therapy response were evaluated based on descriptive statistics. The therapeutic efficacy of vincamine was clearly demonstrated by confirmatory analysis as the drug was statistically significantly superior to placebo in all four target variables. The clinical relevance of the outcome was further underlined by the results of the responder analysis of the variables SCAG, BGP and SKT. Based on the results of this trial, it can be accepted that the therapeutic effect of vincamine is superior to placebo in patients with mild to moderate dementia of degenerative and vascular etiologies.

Divergent neuroprotective effects of nimodipine in PDD and MID provide indirect evidence of disturbances in Ca2+ homeostasis in dementia.

Evidence suggesting that increased cytotoxic Ca2+ concentrations due to disturbances of Ca2+ homeostasis are involved in neuronal deterioration in dementia has accumulated but has not yet been explicitly confirmed. Here we report of divergent neuroprotective effects of nimodipine, a Ca2+ channel blocker with high lipophilic properties, in primary degenerative dementia (PDD) and multiinfarct dementia (MID). Our clinical data show that nimodipine improves clinical symptomatology and cognitive functions in dementia significantly better than placebo but is more effective in PDD than in MID. This fact becomes explicitly apparent by comparison of the mean value differences of each of the 18 SCAG items between onset and termination of treatment in the two diagnostic groups. The divergent therapeutic response in PDD and MID suggests that the neuroprotective effects of nimodipine can not be due mainly to unspecific cognition enhancing mechanisms or vasodilatation of cerebral blood vessels but must primarily be the consequence of a direct activity in depolarized neuronal cells and of its ability to protect neuronal tissue from Ca2+ overload. Hence, we conclude that disturbances in Ca2+ homeostasis play an important role in the process of neuronal deterioration in dementia. Although we can not entirely rule out the possibility that pharmacological activities besides the modulation of neuronal Ca2+ influx contribute to the effects of nimodipine, from a clinical view our results provide indirect evidence of disturbances in Ca2+ homeostasis as one of the primary factors in the demential process. Our results further support the usefulness of nimodipine in the pharmacotherapy of age-related mental deficits.

EEG mapping and psychopharmacological studies with denbufylline in SDAT and MID.

Computed tomography (CT), electroencephalograms (EEG), clinical and psychometric data were obtained in 96 mildly to moderately demented patients (72 women, 24 men), aged 61-96 years (mean 82), diagnosed according to DSM-III criteria. Patients were off drugs for at least 2 weeks and subdiagnosed according to the modified Marshall-Hachinski ischemic score and CT in 45 senile dementia of the Alzheimer type (SDAT) and 51 multiinfarct dementia (MID) patients. Evaluations were carried out before and 12 weeks after treatment with either 100 mg denbufylline BID or placebo and included EEG mapping, the Sandoz Clinical Assessment Geriatric (SCAG) score/factors, the Clinical Global Impression (CGI), the Digit Symbol Substitution Test (DSST), the Trail-Making Test (TMT) and the Digit Span Test (DS). Descriptive data analysis including confirmatory statements found delta/theta activity enhanced, alpha and beta activity reduced, total power augmented, and the centroid slowed down over various brain regions in patients as compared with controls. The two subtypes of dementia could be differentiated in some conventional EEG variables but mostly by means of power asymmetry indices. Denbufylline induced a statistically significant and clinically relevant improvement in both SDAT and MID patients, whereas after placebo this was not the case in CGI, the TMT, and the DS, with interdrug differences being significant in all primary target variables such as the CGI, MMS, SCAG, and DSST. Thus, both the degenerative and vascular type of dementia exhibited a therapeutic benefit that could be objectified at the neurophysiological level by EEG mapping in an improvement of vigilance.

Therapeutic efficacy of pyritinol in patients with senile dementia of the Alzheimer type (SDAT) and multi-infarct dementia (MID).

This trial was performed to investigate the efficacy of pyritinol in the treatment of senile dementia. Initially, a total of 183 inpatients were screened for eligibility. Of 164 patients who met the inclusion criteria, 156 completed the trial. Allocation of the patients to the Senile Dementia of the Alzheimer Type group or the Multi-Infarct Dementia group was based on the Hachinski Ischemic Score, computed tomography scans and electroencephalographic (EEG) findings. In a 12-week double-blind treatment phase either 200 mg pyritinol dihydrochloride-monohydrate or placebo was given 3 times daily. Confirmatory statistics included item 2 of the Clinical Global Impression, the total score of the Short Cognitive Performance Test (Syndrom Kurz Test) and the factor 'cognitive disturbances' of the Sandoz Clinical Assessment Geriatric scale. In addition, data on tolerance, of EEG brain mapping and of a responder analysis were evaluated based on descriptive statistics. The therapeutic efficacy of pyritinol was clearly demonstrated by confirmatory analysis as the drug was statistically significantly superior to placebo in all 3 target variables. The clinical relevance of the outcome was underlined by the analysis of the descriptive variables and by the convergence found at the different observation levels. The EEG mapping demonstrated significant differences between placebo and pyritinol, with the latter decreasing slow and increasing fast alpha and beta activity, which reflects improvement of vigilance. Based on the results of this trial, it can be accepted that the therapeutic effect of pyritinol is superior to placebo in patients with mild to moderate dementia of both degenerative and vascular etiology.

EEG brain mapping in diagnostic and therapeutic assessment of dementia.

EEG brain mapping has been proven to be a valuable method in diagnostic and therapeutic assessment in dementia trials, because it is a readily available, inexpensive, high time-resolution method for objective and quantitative evaluation of the neurophysiological aspects of dementias. In 111 mildly to moderately demented patients diagnosed according to DSM-III as both degenerative [senile dementia of the Alzheimer type (SDAT)] and vascular [multi-infarct dementia (MID) type], we were interested in showing not only differences between SDAT and MID patients and normal controls but also the relationship between CT scans, EEG maps, clinical ratings and psychometric tests. CT measures included 10 cerebrospinal fluid (CSF) space variables as well as 17 cortical density measures (1.7 mm3 cubes, Hounsfield units). Clinical investigations consisted of the SCAG score/factors, the digit symbol substitution test, the trailmaking test and the digit span forward test. In brain maps, SDAT patients showed slightly to moderately more slow and less alpha and beta activity as well as a slowing of the dominant frequency (DF) and the centroid (C) than did normal controls. These findings were most prominent in parietal and temporal regions. MID patients exhibited markedly augmented delta/theta and attenuated alpha and beta activity and a slowing of the DF and C. These neurophysiological findings suggest a deterioration of vigilance. Differences between SDAT and MID patients were found mostly in measures concerning differences in the maps. Brain maps of correlation coefficients between CT and EEG variables demonstrated: the greater the anterior horn distance, lateral ventricle distance, and Evan's index, as well as the less cortical density, the more delta/theta and the less alpha and beta activity in the EEG. Moreover, the higher the delta/theta, the less alpha and beta activity, the higher the SCAG scores, and the worse the psychometric performance. From the pharmacological point of view, we observed a significant improvement in vigilance after administration of several nootropic drugs both in normal and pathologically aging subjects, which was associated also with improvement of psychopathometric scores. Based on multi-variante analysis of variance (MANOVA)/Hotlelling T2 we observed a drug's effect in different brain regions of MID and SDAT patients. Thus, pharmaco-EEG mapping mediates valuable information regarding if, how, when, in which dosage, and where a nootropic drug acts on its target organ--the aging human brain.

Efficacy of xantinolnicotinate in patients with dementia.

Activation of cerebral metabolism and improvement of microcirculation by influencing rheological parameters are claimed to be the underlying pharmacological principles responsible for the efficacy of xantinolnicotinate. This dual mechanism of action led the authors to perform a double-blind, randomized, placebo-controlled study in patients with mild to moderate dementia (DSM III), characterized by a score of 40-90 on the Sandoz Clinical Geriatric Scale (SCAG), with a separate randomization for patients with Multi-Infarct Dementia (MID) and Senile Dementia of Alzheimer Type (SDAT). It was calculated that 150 patients would have to be recruited for each group. Allocation to the respective group (MID or SDAT) was based on the Hachinski Ischemic Score and computer tomogram. Preceded by a 2-week placebo run-in period, a 12-week treatment period followed with either 3 x 1 g xantinolnicotinate (Complamin) or placebo. Prior to the study, the physician's rating of the global therapeutic effect from the clinical global impression (CGI) was designated as the primary criterion of efficacy. Secondary efficacy criteria were SCAG, the BGP nursing rating, and, as psychometric variables, tests from the Nuremberg Psychogeriatric Inventory (NAI). The improvement compared to placebo was statistically significant for the CGI in both treatment groups (p less than 0.0001) and hence independent of etiology. Concerning the nurses' rating (BGP), apart from a marginally statistically significant difference for the factor "need of help" in the SDAT group, no remarkable changes were registered during treatment. However, in the SCAG the differences between verum and placebo were significant (MID p less than 0.0002; SDAT p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)