- Email: [email protected]
P.4.043 DemTect: Final English version of a new cognitive screening test for mild cognitive impairment and early dementia
I?4. Degenerative
and
Design: 286 patieuts were randomized in a double-blind study to either 52 weeks of douepezil treatment (5 “g/day for 4 weeks followed by 10 “g/day, where possible) or placebo. 157 patients who completed the double-blind study theu eutered iuto a 2-year, open-label exteusiou study. All patients in the open-label study received douepezil 5 mglday for 4 weeks followed by 10 “g/day, where possible. Methods: Safety aud tolerability were assessed at Weeks 12, 24, 52 aud every 6 mouths thereafter. The assessments included discoutiuuatiou rate, compliance aud adverse eveuts (AEs). Results: Of the 157 patients who completed the l-year doubleblind study aud enrolled iuto the 2-year exteusiou study, 81 received coutiuuous douepezil treatment for 3 years aud 76 had a delayed treatment start, ie received placebo for oue year followed by douepezil for 2 years. The baseline characteristics betweeu the two treatment groups were similar, with a meau patient age of 71 years aud female patients comprising 63% of the study population During the 2-year exteusiou period 31% of patients coutiuuously treated with douepezil aud 24% of patients in the delayed-start cohort withdrew from the study. The ammalized discoutiuuatiou rate of approximately 13% during this period was lower thau the 30% discoutiuuatiou rate that occurred during the l-year double-blind study. Compliance rates over the twoyear exteusiou period were high ~ greater thau 90% ~ in both cohorts. For the patients who discoutiuued, 10 (12.3%) in the coutiuuously treated douepezil group aud 6 (7.9%) in the delayedstart cohort withdrew due to AEs. Over the 3-year study period, treatment-emergeut AEs were recorded for the majority of patients in both treatment groups; 96.3% coutiuuously treated patients compared with 97.4% delayed-start patients. Commonly reported AEs included the typical choliuergic side effects of choliuesterase iuhibitors such as nausea, diarrhea, headache, aud vomiting, which were rated as either mild or moderate in severity. In both cohorts the first occurrence of these AEs were observed more frequently during Year 1, the double-blind period, thau during the 2-year exteusiou study. Conclusions: Data from this study show that douepezil has au excellent long-term safety profile aud is well tolerated over time in AD patients, with the first occurrence of treatment-emergeut AEs being reported less frequently as therapy coutiuues. The relatively low rate of discoutiuuatiou aud high rate of compliance of this elderly populatiou during the study suggests that these patients are able to tolerate aud persist with douepezil treatment in the loiig term.
neurological
042
Gene expression lymphocytes
profiling
J. Kiliniii’ , A. Zvara2, K. Kitajka3, A. L. Puskas2, Z. Jauka’ ‘University of Szeged, Hungary; 2Biological Research Functional Genomics, Szeged, Hungary; Centel; Institute of Biochemistry, Szeged, Szeged, Alzheimer’ s Disease Research
of Alzheimer’s
Juhasz’, M. Pakaski4, Szeged, Psychiatry, Centel; Laboratory of 3Biological Research Hungary; 4 University of Centel; Szeged, Hungary
Background: Ionic aud signal trausductiou alteratious aud elevated levels of oxidative DNA damage has beeu found in lymphocytes from AD [ 11. These cells show iucreased vuhlerability to programmed cell death [2]. Since the fuuctiou aud metabolism of peripheral lymphocytes is kuowu to be altered in Alzheimer’ s dementia, a pilot study was carried out to examine differences in geiie expressioii profiles.
s403
Subjects and methods: Sixteeu probauds were involved in this study. Eight of them were considered as non-demented, 11011 depressed healthy controls (CNT) aud eight probauds had the diagnoses of Alzheimer’ s disease according to the criteria of Iuteruatioual Classification of Diseases (ICD-10) aud NINCDSADRDA. The RNA was purified from lymphocytes with NucleoSpiu RNA purification kit according to the manufacturer’ s instructions. Microarrays were performed as described earlier [3]. Real-time quantitative reverse trascriptase-PCR was perfonned with gene-specific primers aud SybrGreeu protocol to co&inn the geue expression chauges observed by microarrays. The SPSS 9.0 program for Windows was used for all statistical analyses. Results: By a cDNA microarray represeutiug 3200 distinct human genes, we ideutified 20 candidate genes whose expression is altered in AD lymphocytes compared to CNT. Among these were the alpha2C-adreuoreceptor gene, known to regulate blood pressure, aud learuing, the defeusiu, histocompability complex euhaucer-binding protein, carboxypeptidase M, Fc fragment of IgE knowu to be involved in cellular aud humoral immuue respouses. Others, like human cell death protein, TRAIL, galectiu-4 participate in the regulation of apoptosis. Real-time QRT-PCR analysis was perfonned in order to coufinn the expression chauges in AD lymphocytes aud it could detect downregulation of defeusiu aud alpha2C-adreuoceptor genes, while other genes seemed unaltered in their expression, iucludiug hsp90, CET aud apoB 100. Conclusion: The altered expression profile of these genes might be comlected with the previously reported AD specific lymphocyte abuonnalities. It remaius to be elucidated however, how these genes are related to the pathomechauism of dementia aud whether the geue expression differences of AD lymphocytes reflect disease trait or stage processes. References [l]
M&xz, M., K&&n, J., Juhisz, A., Sinkb, I., McGlynn, AX, Dowries, C.S., Janka, Z., Raskb, I.: Elevated levels of &dative DNA damage in lymphocytes from patients with Alzheimer’ s disease. Neumbiol. Aging, 2002: 23:47-53. M., Muller, WE.: PI Eckeit, A., Cotman, CW., Zerfass, R., Hemmici, Lymphocytes as cell model to study apoptosis in Alzheimer’ s disease: Vulnerability to programmed cell death appears to be altered. J. Neural. Transm. Suppl., 1998; 54: 259-267. G., r31 Kitajka, K., Puskas, L.G., Zvara, A., Hackler, L., Barcelo-Coblijn, Yea, Y.K., Farkas, T.: The role of n-3 polyunsaturated fatty acids in brain: modulation of rat brain gene expression by dietary n-3 fatty acids. Proc. Natl. Acad. Sci. USA, 2002; 99: 2619-2624.
lP.4.0431 mP4
disorders
DemTect: cognitive impairment
Final English version of a new screening test for mild cognitive and early dementia
.I. Kessler’ E. Kalbe2, P. Calabrese3, B. Smith4, P Passmore5, R. Bullock’. ‘Max-Planck-Institute for Neurological Research, Neurology, Cologne, Germany; 2 University Hospital, Neurology, Cologne, Germany; 3 University Hospital, Neurology, Bochum, Germany; 4Memory Assessment Centre, Neurology, Bradford, United Kingdom; ‘Queens University, Geriatric Medicine, Belfast, United Kingdom; 6Kingshill Research Centre, Neurology, Swindon, United Kingdom Introduction: The DemTect is a uew highly sensitive tric screeuiug that was specially designed to detect mild cognitive impainneut @ICI) aud patients with early stages of the disease. The test: It consists of A word list: After pilot study it was found that a
psychomepatients with dementia in 5 subtests.1) word list of
s404
I?4. Degenerative
and
10 items aud two trials is adequate to assess verbal memory in dementia. The items were easy to imagine, comparable in syllable length aud phonological difference. 2) Number trauscodiug task: Two arabic munbers that habe to be couverted iuto number word, aud two number words to do the opposite. 3) Word fluency task: The supermarket task was selected. 4) Digit spau reverse. 5) Delayed recall of the word list. Thus the test covers a broad rauge of cognitive abilities. It is short (S-10 minutes), easy to haudle aud also provides age aud education corrected scoring. Patients aud results: For the uormatiou of the English DemTect version, a total of 145 control subjects (control group (CG) meau age 64.4 years, SD~l0.6, rauge 45589) w h o were classified as cognitively unimpaired by meaus of the Clinical Dementia Rating Scale (CDR) (Hughes et al., 1982), (CDR score=O) were included in the study. Furthermore, 121 patients with possible Alzheimer s disease (AD) according to the NINCDS-ADRDA criteria @lcKhaml et al., 1984) (mean age 73.2 years, SDT9.1, rauge 45592), aud mild to moderate dementia with CDR scores of 1 or 2, aud 97 patients with MCI according to the Peterseu criteria (meau age 72.1, SDT9.0, rauge 45589) with a CDR score of 0.5, were enrolled in the study. All patients uuderweut detailed neurological aud psychiatric examinations iucludiug standard laboratory tests, ultrasound examination, aud magnetic resouauce tomography or computer tomography. After trausformiug the raw scores of the subtests, the young aud old CG had a total score of 15.3 1 (2.53) resp. 15.15 (2.21), the mild AD patients 4.88 (2.1 l), the moderate AD patients 2.36 (1.19), aud the MCI patients 9.71 (2.57). With a maximum score of 18, it helps deciding if a subject s cognitive perfonnauce is age adequate (13-18 points), or if MCI (9912 points) or dementia (8 points or below) has to be suspected. The DemTect has a sensitivity of 80% in MCI patients aud 100% in AD patients. Conclusion: The uew DemTect helps to decide if the cognitive perfonnauce of a subject is age-cousisteut or if MCI or dementia may be suspected. With its high sensitivity for mild cognitive disturbances, its easy administration, aud its iudepeudeucy of sociodemographic factors, it fulfills all essential criteria for a cognitive screeuiug iustrumeut to be used by a wide rauge of professionals such as ueuropsychologists, neurologists or GPs.
m P4
044
Long-term efficacy of donepezil in patients with mild to moderate Alzheimer’s disease: Results from a one-year placebo-controlled study and two-year follow-up study
B. Wiublad’, A. Wimo2, A.-L. Wetterhohn3, A. Hagluud3, K. Eugeda14, H. Soiuiueu5, F.R.J. Verhey’, G. Waldemar7, R. Zhaug’, L. Burger’, R. Schiudle8’. ‘Karolinska Institutet, Alzheimer’ s Disease Research Centel; Stockholm, Swedeq2HC Bergsj, Bergsj, Sweden; 3Pjizer AB, TaDy, Sweden; 4Ulleval University Hospital, Department of Geriatric Medicine, Oslo, Norway; ‘Kuopio University Hospital, Department of Neurology, Kuopio, Finland; 6Academic Hospital Maastricht, Department of Psychiatry, Maastricht, The Netherlands; 7Copenhagen University Hospital, The Neuroscience Centel; Copenhagen, Denmark; 8Pjizer Inc., New York, US.A. Objective: To evaluate the long-tenn efficacy of douepezil 011 global fuuctiou, cognition, aud Activities of Daily Living (ADL) in patients with mild to moderate Alzheimer’ s disease (AD), aud I assess the iuflueuce of a l-year delay in the iuitiatiou of treatment.
neurological
disorders
Design: 286 patients were enrolled iuto a l-year, randomized, double-blind, placebo-controlled study. At cud of Year 1, 81 douepezil-treated aud 76 placebo-treated patients eutered iuto a 2-year open-label exteusiou study. Methods: All patients in the exteusiou study received douepezil, 5 mglday for 4 weeks followed by 10 mglday, where possible, for the 2-year duration Efficacy outcome measures included the Gottfries-Brbue Scale (GBS), the Mini-Meutal State Examination (JvIMSE), the Global Deterioratiou Scale (GDS) aud the Progressive Deterioration Scale (PDS). Patients were assessed at Weeks 12, 24, 36, 52, 78, 104, 130 aud 156. Mixed regression analysis compared chauges 011 these measures betweeu coutiuuously treated douepezil patients aud those with a l-year delayed treatment start, over the 3-year period. A reference projected placebo group was calculated using data from placebo patients during the double-blind period. Results: 56 (69.1%) patients receiving coutiuuous douepezil treatment aud 58 (76.3%) in the delayed-start group completed the 2-year exteusiou study. Patients receiving douepezil for 3 years had significantly less cognitive decline thau those with a delayed start (Overall: P=O.O04). A significant treatment difference in favor of coutiuuous douepezil treatment was observed at Week 156 011 the MMSE (PiO.05). Patients receiving coutiuuous therapy had less global deterioration, measured 011 GBS, thau those who had delayed treatment (P=O.O56). This was supported by the more favorable response of 3 years coutiuuous douepezil treatment compared with a delayed treatment start, as measured by the GDS (PPO.02). As expected, followiug iuitiatiou of douepezil treatment at Year 1, patients origiually randomized to placebo showed a slower fuuctioual decline 011 the PDS, betweeu treatment Weeks 52 aud 78, thau those who received coutiuuous douepezil treatment. By the cud of the study (Week 156) patients in both groups had reached the same level of chauge, although overall, there was a treud in favor of coutiuuous treatment (PDS: P=O.O9). Delayedstart patients showed beuefits in global aud cognitive fuuctiouiug aud ADL compared with the projected placebo group. Conclusions: Patients who received coutiuuous douepezil treatmeut maiutaiued greater levels of global function, cognition aud ADL thau those who had a l-year treatment delay. However, receiving douepezil after a l-year delay in treatment also resulted in beuefits wheu compared with 110 treatment.
mP4
045
Dementia symptoms
patients benefit
with from
additional donepezil
parkinsonian therapy
.I. Kohler’ , K. Jeudroska2, R. Horu3, M. Kamleiter4, .I. Mobiu?, M. Reipe’. ‘Arzt fiir Neurologie, Emmendingen, Germany; 2Berlin, Germany; 3Bad HonneJ Germany; 4Ludwig Maximilian University, Department of Psychiatry, Munich, Germany; ‘Eisai GmDH, Frankjiirt, Germany; 6 University of Ulm, Neurological Clinic, Ulm, Germany Objectives: To compare the safety aud efficacy of douepezil in dementia patients with aud without additioual Parkiusouiau symptoms (PS i). Methods: 2029 Alzheimer patients were enrolled in this Germau post-marketing surveillance study. The effect of douepezil 011 individual problematic symptoms was scored 011 a 5-point Likerttype scale, raugiug from “markedly improved” (+2) to “markedly worsened” (-2). The meau score for each of the individual symptom score “IudiSS” items was calculated at Weeks 12 aud 24.
and
Design: 286 patieuts were randomized in a double-blind study to either 52 weeks of douepezil treatment (5 “g/day for 4 weeks followed by 10 “g/day, where possible) or placebo. 157 patients who completed the double-blind study theu eutered iuto a 2-year, open-label exteusiou study. All patients in the open-label study received douepezil 5 mglday for 4 weeks followed by 10 “g/day, where possible. Methods: Safety aud tolerability were assessed at Weeks 12, 24, 52 aud every 6 mouths thereafter. The assessments included discoutiuuatiou rate, compliance aud adverse eveuts (AEs). Results: Of the 157 patients who completed the l-year doubleblind study aud enrolled iuto the 2-year exteusiou study, 81 received coutiuuous douepezil treatment for 3 years aud 76 had a delayed treatment start, ie received placebo for oue year followed by douepezil for 2 years. The baseline characteristics betweeu the two treatment groups were similar, with a meau patient age of 71 years aud female patients comprising 63% of the study population During the 2-year exteusiou period 31% of patients coutiuuously treated with douepezil aud 24% of patients in the delayed-start cohort withdrew from the study. The ammalized discoutiuuatiou rate of approximately 13% during this period was lower thau the 30% discoutiuuatiou rate that occurred during the l-year double-blind study. Compliance rates over the twoyear exteusiou period were high ~ greater thau 90% ~ in both cohorts. For the patients who discoutiuued, 10 (12.3%) in the coutiuuously treated douepezil group aud 6 (7.9%) in the delayedstart cohort withdrew due to AEs. Over the 3-year study period, treatment-emergeut AEs were recorded for the majority of patients in both treatment groups; 96.3% coutiuuously treated patients compared with 97.4% delayed-start patients. Commonly reported AEs included the typical choliuergic side effects of choliuesterase iuhibitors such as nausea, diarrhea, headache, aud vomiting, which were rated as either mild or moderate in severity. In both cohorts the first occurrence of these AEs were observed more frequently during Year 1, the double-blind period, thau during the 2-year exteusiou study. Conclusions: Data from this study show that douepezil has au excellent long-term safety profile aud is well tolerated over time in AD patients, with the first occurrence of treatment-emergeut AEs being reported less frequently as therapy coutiuues. The relatively low rate of discoutiuuatiou aud high rate of compliance of this elderly populatiou during the study suggests that these patients are able to tolerate aud persist with douepezil treatment in the loiig term.
neurological
042
Gene expression lymphocytes
profiling
J. Kiliniii’ , A. Zvara2, K. Kitajka3, A. L. Puskas2, Z. Jauka’ ‘University of Szeged, Hungary; 2Biological Research Functional Genomics, Szeged, Hungary; Centel; Institute of Biochemistry, Szeged, Szeged, Alzheimer’ s Disease Research
of Alzheimer’s
Juhasz’, M. Pakaski4, Szeged, Psychiatry, Centel; Laboratory of 3Biological Research Hungary; 4 University of Centel; Szeged, Hungary
Background: Ionic aud signal trausductiou alteratious aud elevated levels of oxidative DNA damage has beeu found in lymphocytes from AD [ 11. These cells show iucreased vuhlerability to programmed cell death [2]. Since the fuuctiou aud metabolism of peripheral lymphocytes is kuowu to be altered in Alzheimer’ s dementia, a pilot study was carried out to examine differences in geiie expressioii profiles.
s403
Subjects and methods: Sixteeu probauds were involved in this study. Eight of them were considered as non-demented, 11011 depressed healthy controls (CNT) aud eight probauds had the diagnoses of Alzheimer’ s disease according to the criteria of Iuteruatioual Classification of Diseases (ICD-10) aud NINCDSADRDA. The RNA was purified from lymphocytes with NucleoSpiu RNA purification kit according to the manufacturer’ s instructions. Microarrays were performed as described earlier [3]. Real-time quantitative reverse trascriptase-PCR was perfonned with gene-specific primers aud SybrGreeu protocol to co&inn the geue expression chauges observed by microarrays. The SPSS 9.0 program for Windows was used for all statistical analyses. Results: By a cDNA microarray represeutiug 3200 distinct human genes, we ideutified 20 candidate genes whose expression is altered in AD lymphocytes compared to CNT. Among these were the alpha2C-adreuoreceptor gene, known to regulate blood pressure, aud learuing, the defeusiu, histocompability complex euhaucer-binding protein, carboxypeptidase M, Fc fragment of IgE knowu to be involved in cellular aud humoral immuue respouses. Others, like human cell death protein, TRAIL, galectiu-4 participate in the regulation of apoptosis. Real-time QRT-PCR analysis was perfonned in order to coufinn the expression chauges in AD lymphocytes aud it could detect downregulation of defeusiu aud alpha2C-adreuoceptor genes, while other genes seemed unaltered in their expression, iucludiug hsp90, CET aud apoB 100. Conclusion: The altered expression profile of these genes might be comlected with the previously reported AD specific lymphocyte abuonnalities. It remaius to be elucidated however, how these genes are related to the pathomechauism of dementia aud whether the geue expression differences of AD lymphocytes reflect disease trait or stage processes. References [l]
M&xz, M., K&&n, J., Juhisz, A., Sinkb, I., McGlynn, AX, Dowries, C.S., Janka, Z., Raskb, I.: Elevated levels of &dative DNA damage in lymphocytes from patients with Alzheimer’ s disease. Neumbiol. Aging, 2002: 23:47-53. M., Muller, WE.: PI Eckeit, A., Cotman, CW., Zerfass, R., Hemmici, Lymphocytes as cell model to study apoptosis in Alzheimer’ s disease: Vulnerability to programmed cell death appears to be altered. J. Neural. Transm. Suppl., 1998; 54: 259-267. G., r31 Kitajka, K., Puskas, L.G., Zvara, A., Hackler, L., Barcelo-Coblijn, Yea, Y.K., Farkas, T.: The role of n-3 polyunsaturated fatty acids in brain: modulation of rat brain gene expression by dietary n-3 fatty acids. Proc. Natl. Acad. Sci. USA, 2002; 99: 2619-2624.
lP.4.0431 mP4
disorders
DemTect: cognitive impairment
Final English version of a new screening test for mild cognitive and early dementia
.I. Kessler’ E. Kalbe2, P. Calabrese3, B. Smith4, P Passmore5, R. Bullock’. ‘Max-Planck-Institute for Neurological Research, Neurology, Cologne, Germany; 2 University Hospital, Neurology, Cologne, Germany; 3 University Hospital, Neurology, Bochum, Germany; 4Memory Assessment Centre, Neurology, Bradford, United Kingdom; ‘Queens University, Geriatric Medicine, Belfast, United Kingdom; 6Kingshill Research Centre, Neurology, Swindon, United Kingdom Introduction: The DemTect is a uew highly sensitive tric screeuiug that was specially designed to detect mild cognitive impainneut @ICI) aud patients with early stages of the disease. The test: It consists of A word list: After pilot study it was found that a
psychomepatients with dementia in 5 subtests.1) word list of
s404
I?4. Degenerative
and
10 items aud two trials is adequate to assess verbal memory in dementia. The items were easy to imagine, comparable in syllable length aud phonological difference. 2) Number trauscodiug task: Two arabic munbers that habe to be couverted iuto number word, aud two number words to do the opposite. 3) Word fluency task: The supermarket task was selected. 4) Digit spau reverse. 5) Delayed recall of the word list. Thus the test covers a broad rauge of cognitive abilities. It is short (S-10 minutes), easy to haudle aud also provides age aud education corrected scoring. Patients aud results: For the uormatiou of the English DemTect version, a total of 145 control subjects (control group (CG) meau age 64.4 years, SD~l0.6, rauge 45589) w h o were classified as cognitively unimpaired by meaus of the Clinical Dementia Rating Scale (CDR) (Hughes et al., 1982), (CDR score=O) were included in the study. Furthermore, 121 patients with possible Alzheimer s disease (AD) according to the NINCDS-ADRDA criteria @lcKhaml et al., 1984) (mean age 73.2 years, SDT9.1, rauge 45592), aud mild to moderate dementia with CDR scores of 1 or 2, aud 97 patients with MCI according to the Peterseu criteria (meau age 72.1, SDT9.0, rauge 45589) with a CDR score of 0.5, were enrolled in the study. All patients uuderweut detailed neurological aud psychiatric examinations iucludiug standard laboratory tests, ultrasound examination, aud magnetic resouauce tomography or computer tomography. After trausformiug the raw scores of the subtests, the young aud old CG had a total score of 15.3 1 (2.53) resp. 15.15 (2.21), the mild AD patients 4.88 (2.1 l), the moderate AD patients 2.36 (1.19), aud the MCI patients 9.71 (2.57). With a maximum score of 18, it helps deciding if a subject s cognitive perfonnauce is age adequate (13-18 points), or if MCI (9912 points) or dementia (8 points or below) has to be suspected. The DemTect has a sensitivity of 80% in MCI patients aud 100% in AD patients. Conclusion: The uew DemTect helps to decide if the cognitive perfonnauce of a subject is age-cousisteut or if MCI or dementia may be suspected. With its high sensitivity for mild cognitive disturbances, its easy administration, aud its iudepeudeucy of sociodemographic factors, it fulfills all essential criteria for a cognitive screeuiug iustrumeut to be used by a wide rauge of professionals such as ueuropsychologists, neurologists or GPs.
m P4
044
Long-term efficacy of donepezil in patients with mild to moderate Alzheimer’s disease: Results from a one-year placebo-controlled study and two-year follow-up study
B. Wiublad’, A. Wimo2, A.-L. Wetterhohn3, A. Hagluud3, K. Eugeda14, H. Soiuiueu5, F.R.J. Verhey’, G. Waldemar7, R. Zhaug’, L. Burger’, R. Schiudle8’. ‘Karolinska Institutet, Alzheimer’ s Disease Research Centel; Stockholm, Swedeq2HC Bergsj, Bergsj, Sweden; 3Pjizer AB, TaDy, Sweden; 4Ulleval University Hospital, Department of Geriatric Medicine, Oslo, Norway; ‘Kuopio University Hospital, Department of Neurology, Kuopio, Finland; 6Academic Hospital Maastricht, Department of Psychiatry, Maastricht, The Netherlands; 7Copenhagen University Hospital, The Neuroscience Centel; Copenhagen, Denmark; 8Pjizer Inc., New York, US.A. Objective: To evaluate the long-tenn efficacy of douepezil 011 global fuuctiou, cognition, aud Activities of Daily Living (ADL) in patients with mild to moderate Alzheimer’ s disease (AD), aud I assess the iuflueuce of a l-year delay in the iuitiatiou of treatment.
neurological
disorders
Design: 286 patients were enrolled iuto a l-year, randomized, double-blind, placebo-controlled study. At cud of Year 1, 81 douepezil-treated aud 76 placebo-treated patients eutered iuto a 2-year open-label exteusiou study. Methods: All patients in the exteusiou study received douepezil, 5 mglday for 4 weeks followed by 10 mglday, where possible, for the 2-year duration Efficacy outcome measures included the Gottfries-Brbue Scale (GBS), the Mini-Meutal State Examination (JvIMSE), the Global Deterioratiou Scale (GDS) aud the Progressive Deterioration Scale (PDS). Patients were assessed at Weeks 12, 24, 36, 52, 78, 104, 130 aud 156. Mixed regression analysis compared chauges 011 these measures betweeu coutiuuously treated douepezil patients aud those with a l-year delayed treatment start, over the 3-year period. A reference projected placebo group was calculated using data from placebo patients during the double-blind period. Results: 56 (69.1%) patients receiving coutiuuous douepezil treatment aud 58 (76.3%) in the delayed-start group completed the 2-year exteusiou study. Patients receiving douepezil for 3 years had significantly less cognitive decline thau those with a delayed start (Overall: P=O.O04). A significant treatment difference in favor of coutiuuous douepezil treatment was observed at Week 156 011 the MMSE (PiO.05). Patients receiving coutiuuous therapy had less global deterioration, measured 011 GBS, thau those who had delayed treatment (P=O.O56). This was supported by the more favorable response of 3 years coutiuuous douepezil treatment compared with a delayed treatment start, as measured by the GDS (PPO.02). As expected, followiug iuitiatiou of douepezil treatment at Year 1, patients origiually randomized to placebo showed a slower fuuctioual decline 011 the PDS, betweeu treatment Weeks 52 aud 78, thau those who received coutiuuous douepezil treatment. By the cud of the study (Week 156) patients in both groups had reached the same level of chauge, although overall, there was a treud in favor of coutiuuous treatment (PDS: P=O.O9). Delayedstart patients showed beuefits in global aud cognitive fuuctiouiug aud ADL compared with the projected placebo group. Conclusions: Patients who received coutiuuous douepezil treatmeut maiutaiued greater levels of global function, cognition aud ADL thau those who had a l-year treatment delay. However, receiving douepezil after a l-year delay in treatment also resulted in beuefits wheu compared with 110 treatment.
mP4
045
Dementia symptoms
patients benefit
with from
additional donepezil
parkinsonian therapy
.I. Kohler’ , K. Jeudroska2, R. Horu3, M. Kamleiter4, .I. Mobiu?, M. Reipe’. ‘Arzt fiir Neurologie, Emmendingen, Germany; 2Berlin, Germany; 3Bad HonneJ Germany; 4Ludwig Maximilian University, Department of Psychiatry, Munich, Germany; ‘Eisai GmDH, Frankjiirt, Germany; 6 University of Ulm, Neurological Clinic, Ulm, Germany Objectives: To compare the safety aud efficacy of douepezil in dementia patients with aud without additioual Parkiusouiau symptoms (PS i). Methods: 2029 Alzheimer patients were enrolled in this Germau post-marketing surveillance study. The effect of douepezil 011 individual problematic symptoms was scored 011 a 5-point Likerttype scale, raugiug from “markedly improved” (+2) to “markedly worsened” (-2). The meau score for each of the individual symptom score “IudiSS” items was calculated at Weeks 12 aud 24.