THIRD INTERNATIONAL CONFERENCE ON ALZHEIMER’S DISEASE Sl27

sea. However ) these trials have usually dealt with small groups of patients selected for the presumptive presence of senile dementias. In this double-blind study the therapeutic effects and the sa- fety of orally treatment with phosphatidylserine vs placebo (300 ??g/die for 6 months) was assessed in a group of geria- tric uatients with coanitive impairment. A total of 494 el- derly patients (age between 65 and 93 yrs), affected by mode- rate to severe cognitive decline according to the Mini Mental State Examination and Global Deterioration Scale, were recrui- ted in 23 Geriatric or General Medicine Units in Northeastern Italy. Patients were examined just before starting the therapy, and 3 and 6 months thereafter. The efficacy of treatment compared with placebo was measured on the basis of changes occurring in behavior and cognitive performance using the Plutchik Ge- riatric Rating Scale and the Buschke Selective Reminding Test. Statistically significant improvements in the phosphatidylse- rine-treated group compared with placebo were observed both in terms of behavioral and cognitive parameters. Clinical eva- luation and laboratory tests demonstrated that phosphatydilse- rine was well tolerated. These results are particular relevance in the light of the large number of patients enrolled in this study, who repre- sent a sample of the geriatric population commonly encounte- red in clinical practice.

501 ORAL TE TRAHYDROAMINOACRIDINE (THA) TREATMENT OF ALZHEIMER’S DISEASE. EVALUATED CLINICALLY AND BY REGIONAL CEREBRAL BLOOD FLOW (rCBF) AND EEG. L Minthon, L Gustafson, G DaJfelt, B Hagberg, I Ros&, J Risberg, K Nilsson and PE Wendt. Depts of Psychogeriatxics and Clinical Neurophysiology and Geronto- logy Research Center, University HosuitaJ, P.O. Box 638, 220 09 Lund, &&den.

- . Previous studies of physostigmin and teaahydroaminoacridine (THA) treat- ment of dementia of Alzheimer type @AT) have indicated positive effects on cognition and neumphysiological measures. The present study evaluated oral THA-aeatment with and without lecithin compared to placebo in patients with TIAT -.__, Seventeen patients (8 women and 9 men) with a mean age of 63 +/- 7 (range 51-77) years were selected for the study. The study had a double-blind crossover design with three 6-week treatment periods with two drugfree week inbetween. The sequence of treatments, THA+lecithin, THA+placebo and placebo+placebo, was randomized. The patients first went through a neuro- psychiatric investigation, including regional cerebral blood flow (rCBF) measurements, EEG, cexebrospinal fluid (CSF) analysis and in most cases CT. The clinical effects wen measured at baseline and aftex 3 and 6 weeks during each treatment period. The evaluation was based on the organic brain syndrome (OBS) scale, a rating scale for side effects, the psychomeuic testbatteq, rCBF measurement, EEG and laboratory tests. All 17 patients went through the full design of the study. The mean dose of THA was 103 +/- 23 mg/day (range 50-125 mg). Three patienu showed marked elevations of ALT and AST during THA treannent, with normalization following dose reduction. The total patient group showed no significant clinical improvement during THA treatment compared to placebo. There were however important individual differences. Six patients were responders, five patients were mainly unchanged and six patients deteriorated further during the 26 weeks study. rCBF in frontotemporal areas was significantly higher in responders companxl to deteriorated patients at the pm-treatment measure- ment. Nine patients continued THA treatment in an open uial. They have been compared to a control group of eleven unmated DAT patients with identical pre-treatment rCBF values. rCBF was after one year significantly higher in the parietal cortex in the THA treated patients. The results are compatible with an enhancement of cortical and subcortical choline@ functions.

502 A DOUBLE BLIND, PLACEBO AND PIRACETAM CONTROLLED, MULTICENTER TRIAL OF VINPOCETINE IN DEMENTIA OF

ALZHEIMER’S TYPE AND VASCULAR DEMENTIA.

E.Ch. Walters’, Ph. Scheltens’, J. Zwart’, L.Persijn’, C. MI&, H. van Genuchten’, A. Li%ventha@, C. Sennef’.

Introduction: Vinpocetine (Org 30759) is an eburnamemine derivative which improves oxygen utilization and tolerance to hypoxia of brain tissue, improves cerebrovascular perfusion and enhances glucose uptake.

Objective: To test the effect of Vinpocetine on cognitive and/or behavioral disturbances, as compared to Placebo and Piracetam, in a double blind multicenter study, in vascular (VD) and Alzheimer’s dementia (AD) patients. Methods: 53 male and 57 female (21 VD, 89 AD) patients entered the study. Efficacv was measured bv alobal efficacv oarameters (CC1 and SKT). cognitiie efficacy parameters (:CRS and psychometrics) as &I as the SCAG.” Results: After 3 months of treatment 90/l 10 of the patients were evaluable for efficacy analysis. Vinpocetine was well tolerated. No clinical meaningful1 side effects were noted on several biological parameters. No statistically significant differences were seen between the three treatment regimens in the mean change from baseline to last assessment for any of the efficacy parameters. Significant improvement was observed in the Vinpocetine treatment group only for the Affect variable of the SCAG, between first and last assessment (p<O.O5). The results were the same when the DAT and VD patients were analysed separately. However, in a subgroup of moderately demented patients (SKT > 13) (N=62), patients receiving placebo (N=25) appeared to be deteriorated significantly (p<O.O5) on both the SKT and the SCAG on the last assessment as compared to both baseline and treatment with either Vinpocetine (N=17) or Piracetam (N-20). Conclusions: Vinpocetine and Piracetam are well tolerated drugs, which do not induce clinically significant improvement in (VD & AD) demented patients. However, as compared with placebo they may (temporarily) prevent further deterioration in moderately demented patients.

503 A CLINICAL STUDY OF CEREBROLYSIN (FPF1070) ON SENILE DEMENTIA

M. TAKAHASH I, Y. NAKAMURA, Depts of Neurology, Kinki University School of Medicine, Osakasauama. Japan. M. FUJIMOTO. H. SEKI. T. ONO, Habikino laboratory, Fujimoto Diagnostics I NC. Mathubara, Japan

Cerebrolvsin(FPF1070) is an extract from Protein fraction of pig brain and has been considered to have some action Ii ke nerve growth factor. We studied its efficacy and safety on 14 Patients with cerebrovascular dementia and on 8 Patients with dementia of Alzheimer’s type . Patients received intravenous injection of 5 to 1Oml once a dav for 4 or 8 weeks. Hasegawa’s Dementia Scale(HDS), Mini-Mental State Examination(W) and modified Gottfries. Brane. Steen Scale(GBS) were used for the evaluation of this drug. Remarkable or moderate improvement ratings of HDS, MWS and GBS on the patients were 50.0%, 20.0% and 50.0%. respectively. The intellectual functions(memoru and orientation) and enthusiasm were improved in various degrees. On the other hand, favourite effects were not found in the responses to various commands in MMS. Remarkable or moderate improvement ratings of HDS,MMS and GBS on the Patients with cerebrovascular dementia were 59.1%. 30.8% and 84.3% respectively. while 37.5%. 0% and 25.0% on the patients with dementia of Alzheimer’s type. NO side effects were observed and there was no noticeable abnormality in the clinical laboratory tests. From the above results, it was considered that FPF1070 has a high Possibility of useful drug on senile dementia.

504 THE EFFECTS OF CEREBROLYSINR ON SURVIVAL AND SPROUTING OF NEURONS PROM CERBBRAL =SPHERES AND FROM THE BRAINSTEM OF CHICKEN EMBRYOS IN VITRO

E. AJBREXHT, S. HINGBL, K CRAILSHEIM, M. WINDISCH Inst. Zool.;Dept. Metabolic Physiol.;Univx&it Graq Austria

Cerebrolysin, a drug produc.zd by biotechnological methods, using a stauderdized enzymatic breakdown of pig brain proteins, i widely used in the. therapy of neurodegenerative, ischemic and traumatic cerebral disorders. To study the e!Teets of Cerebrolysin sod the basic tibroblast growth factor hPGF, mecbanicaUy d&&w! ueurons born cerebral bemiapberes of chick embryo (ES), cukured al a densily of 75 asI cew16 mm weU (poly-Iysine coated) in a serum contaiuiag medium wre used (Petman