additional cohort received lecozotan SR 10mg once daily or placebo (11active, 5 placebo) for 28 days. Safety evaluations included adverse events(AE), vital signs, ECG, and lab tests; patients also were administered theADAS-Cog at baseline and day 28. Lecozotan pharmacokinetics weredetermined by noncompartmental analysis on days 1 and 28. Results:Lecozotan was well tolerated after multiple dosing for 28 days. Most AEswere mild to moderate in severity and included headache, dizziness, con-stipation, insomnia, and pruritus. One serious AE (lacunar infarct) occurredin the lecozotan-treated group. AE frequency was substantially reduced inthe SR-treated group compared with the IR-treated group. Lecozotan tmax

was � 1.5 hour (IR) and 4-8 hours (SR). Elimination t1/2 was 7 - 14 hours.Linear dose proportionality was seen for Cmax and AUC over the 0.5 to 5.0mg dose range. Based on AUC0-�, lecozotan SR was bioequivalent to IR.ADAS-Cog results showed a trend toward improvement over baseline atday 28 for the groups receiving 10mg/day lecozotan. Conclusions: Leco-zotan appeared to be safe in AD subjects up to daily doses of 10 mg. Therewere no significant differences in the elimination properties of lecozotanbetween the two formulations. The SR formulation was better toleratedthan the IR formulation, possibly due to reduced lecozotan peak plasmaconcentration.

P3-461 EFFECTS OF PHARMACOLOGICALTREATMENT IN PATIENTS WITH DEMENTIA

Paulo Renato Canineu, Canineu, PRB, Canineu, RFB, Silva, MC,Pontifıcia Universidade Catolica de Sao Paulo, Sorocaba, Brazil.Contact e-mail: canineu@splicenet.com.br

Objectives: To analyze the results of treatment in a group of elderlypatients with dementia followed during a two-year in a geriatric clinic inSorocaba City, Brazil. Methods: This research is two years longitudinalretrospective study, analyzing 102 elderly, who had the dementia diagnosisaccording to the DSMIV and NINCDS-ADRDA criteria and were super-vised by the same geriatric physician along the time. All patients wereevaluated by MMSE, Clock Drawing, Verbal Function and Proverb Inter-pretation before the treatment and every 6 months. They were also eval-uated by KATZ and PFEFFER Scales. There were 5 groups related withthe drug utilized: Donepezil (7 patients); Galantamine (7 patients); Riv-astigmine (49 patients); Memantine (11 patients) and Memantine � ChEi(15 patients). All the patients were in a mild or moderate stage of dementia.They were classified after the treatment as: worse (lost more than 3points/year in the MMSE); stabilized (lost less than 3 points) and improved(no points lost). Thirteen patients didn’t complete treatment. Results:Among the patients 65 had Alzheimer’s Disease (63.73%), 13 VascularDementia (12.74%), 16 Mixed Dementia (15.68%), 6 Frontotemporal De-mentia (5.88%), 1 Parkinson’s Disease (0.99%) and 1 Huntington’s Dis-ease (0.99%). Of the 7 patients treated with Donepezil: 4 were worse(57.10%), 2 stabilized (28.50%) and 1 improved (14.20%). Of the 7 withGalantamine: 3 were worse (42.80%), 4 stabilized (57.10%) and no oneimproved. Of the 49 with Rivastigmine: 17 were worse (34.70%), 24stabilized (48.90%) and 8 improved (16.30%). Of the 11 with Memantine:1 was worse (9.90%), 6 stabilized (54.50%) and 4 improved (36.30%). Ofthe 15 with Memantine�ChEi: 3 were worse (20.00%), 10 stabilized(66.60%) and 2 improved (13.30%). Summarizing: 28 were worse(32.90%), 46 stabilized (43.10%) and 15 improved (16.19%). Conclu-sions: It is possible to interfere in the dementia process by pharmacologicaltreatment. It seems that all the drugs may improve the dementia patients’and caregivers’ quality of life, but Rivastigmine, Memantine andMemantine�ChEi may act better than the others.

P3-462 A RANDOMIZED, DOUBLE-BLIND, PLACEBOCONTROLLED-TRIAL OF TRIFLUSAL IN MILDCOGNITIVE IMPAIRMENT

Teresa Gomez-Isla1, Genıs Munoz2, Jose M. Ferro3,Jose Manuel Martınez Lage4, Jose Carlos Navas Ramırez5, 1HospitalSanta Creu i Sant Pau, Barcelona, Spain; 2J. Uriach y Companıa, S.A.,

Barcelona, Spain; 3Hospital Santa Maria, Lisbon, Portugal; 4ClınicaUniversitaria de Navarra, Pamplona, Spain; 5J.Uriach y Companıa,S.A., Barcelona, Spain. Contact e-mail: mgomezi@santpau.es

Background: Mild cognitive impairment (MCI) represents in many casesthe earliest clinical phases of Alzheimer’s disease (AD). From a practicalperspective, the identification of the earliest stages of dementia and ADwill allow interventions in the disease process when a therapy might still beeffective. Anti-inflammatory agents have epidemiological support as drugspotentially beneficial in AD, but so far clinical trials have been disappoint-ing. In vivo studies have shown that triflusal and its active metabolite HTBhave anti-inflammatory actions in the CNS by inhibiting NF-kappa Bactivation. Objective(s): Based on this rationale, a randomized, double-blind, placebo controlled-trial of triflusal in amnestic MCI patients(TRIMCI) was conducted in Spain and Portugal. Methods: Subjects wererandomly assigned to receive 900 mg of triflusal or placebo for 18 months.The primary outcome was a change in Cognitive subscale of the Alzhei-mer’s Disease Assessment Scale (ADAS-cog); secondary outcomes wereconversion to dementia, a change in a battery of neuropsychological tests,and brain MRI volumetric measurements, among others. Results: A veryslow rate of recruitment forced a premature cessation of the study. A totalof 257 subjects were enrolled and followed-up for an average of 13 months.Intention to treat analysis did not show significant differences in ADAS-cog scores in the comparison among groups (p � 0.096). However, perprotocol analysis, the difference reached statistical significance (p �0.040). The overall rate of progression from MCI to dementia was 16percent. As compared with the placebo group, there were significantdifferences in the probability of progression to dementia in the triflusalgroup (hazard ratio, 2.10; 95 percent confidence interval, 1.10 to 4.01; p �0.024; adjusted analysis by baseline ADAS-cog and geographical zone).Conclusions: In this study triflusal therapy was well tolerated and associ-ated with a lower rate of progression to dementia. Because the trial wasprematurely halted, these results should be interpreted with caution andrequire further confirmatory studies.

P3-463 “DAD’S BACK” - TREATMENT EFFECT ANDPERSONALITY IN ALZHEIMER’S PATIENTSENROLLED IN A MULTI-CENTERGALANTAMINE TRIAL

Sherri Fay, Kenneth Rockwood, Dalhousie University, Halifax, NS,Canada. Contact e-mail: FAYSL@cdha.nshealth.ca

Objectives: Anecdotal reports suggest that an important but formallyundetected treatment effect described by caregivers and patients is thereturn of the person they knew pre-onset of AD (“Dad’s back”). Weinvestigated whether this treatment effect occurred in the VISTA database.Methods: We studied 75 mild to moderate AD patients who participated inthe Video Imaging Synthesis of Treating Alzheimer’s disease (VISTA)Study, a 4-month, multi-center, parallel group double-blind placebo-con-trolled trial of galantamine (16-24 mg/day) with a 4-month open labelfollow-up. Standard efficacy parameters were captured at baseline andfollowed monthly and, in addition, the patient and primary caregiverparticipated in the Clinician’s Interview Based Impression of Change-PlusCaregiver Input (CIBIC-Plus) and Goal Attainment Scaling (GAS), whichwere digitally videotaped and then qualitatively coded. Searches, blindedto treatment effect assignment, were carried out on the baseline data for 75patients, looking for reports of change in personality (e.g. “she used to bethe life of the party”) and then tracking these at two and four months, tolook for their return. Results: 27 of 75 patients (36%) were reported atbaseline to have declined in an area characteristic to them. (“He was sofunny, but he’s lost his sense of humour.”) 48 problem areas were found inthese 27 patients. Of these 48, 27 (56%) were in interpersonal behavior andrelations (socializing, socially inappropriate behaviors, irritation with oth-ers), 8 (17%) were in functional areas, 7 (15%) were in cognitive areas, 4(8%) in leisure activities and 2 (4%) in areas of behavior not affectingsocializing (e.g. hoarding). By month four, 12 patients (44%) had improved

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