- Email: [email protected]
P3-456
S510
Poster P3:: Tuesday Posters
pected of having ongoing bacterial infection with Borrelia, long term antibiotic therapy (6 months) will be instituted along with 200 hrs of DC EMF therapy. A parallel trial of Alzheimer patients diagnosed with Lyme by ILADS criteria with 6 months of Doxycycline/ Tindazole without DC electromagnetic therapy is also planned.
P3-455
DONEPEZIL TREATMENT FOR ALZHEIMER’S DISEASE IN CHRONIC DIALYSIS PATIENTS
Konstantina G. Yiannopoulou, Athina K. Euthymiou, Kleanthis D. Karydakis, General Hospital of Athens, Athens, Greece. Contact e-mail: [email protected] Background: Donepezil is one of the cholinesterase inhibitors that are indicated for the treatment of mild to moderate Alzheimer’s Disease. Pharmacokinetic analysis has shown that donepezil is primarily eliminated by renal excretion rather than biliary excretion in humans. Therefore, patients with impaired renal function are at high risk for toxicity caused by accumulation of this drug. It is also well known that dialysis patients have very often cholinergic disorders. On the other hand, with the increasing number of long-term chronic dialysis patients, the prevalence of cognitive disorders is increasing in the elderly of them. Because of the above mentioned special risks, prescription of acetylocholinesterase inhibitors, such as donepezil, to be avoided is prescribed. There is only one study that evaluates the pharmacokinetics of donepezil in patients with impaired renal function and only one case-report with donepezil treatment in a chronic-dialysis patient. Objectives: This pilot study aimed to investigate whether there is a safe dose of donepezil to be administered in chronic dialysis patients with Alzheimer’s disease and if this treatment offers a possible benefit to them. Methods: We studied three cases of chronic hemodialysis outpatients (2 men and 1 woman, 72, 86 and 65 years old respectively), that were diagnosed as having moderate Alzheimer’s disease. Study subjects underwent a baseline clinical and laboratory assessment and a neuropsychological examination (including MMSE, GDS, NPI and IADL scale), that it was repeated every month. All patients were followed for 6 months. We began treatment with donepezil on the lower dose of 2.5mg/day orally and we enhanced the dose to 5mg/day one month later. Results: After 1 month’s treatment, they improved to a controllable psychiatric condition, without having any adverse effects. After 3 months of treatment with the higher dose, their cognitive and executive functions were slightly improved and their behavior was remarkably improved, without experiencing any episodes of drug toxicity. The patients’ condition remained stable for 6 months after the initial administration of the drug. Conclusion: Our cases indicate that donepezil treatment under prudent use may be well tolerated and have a beneficial impact on chronic hemodialysis patients with Alzheimer’s disease.
P3-456
DIFFERENTIAL QUANTITATIVE EEG EFFECTS OF RIVASTIGMINE AND MEMANTINE IN ALZHEIMER PATIENTS
Georg Adler1, Oliver Hennig1, Eva Grips1, Petra van Keulen2, Martin Roser2, Ferenc Tracik3, Lutz Froelich1, 1Central Institute of Mental Health, Mannheim, Germany; 2Psychiatrisches Zentrum Calw, Calw, Germany; 3Novartis GmbH, Nu¨rnberg, Germany. Contact e-mail: [email protected] Background: In the quantitative EEG of Alzheimer patients, mean theta power is increased and left temporal alpha coherence is decreased. Under treatment with the acetylcholine esterase inhibitor rivastigmine theta power decreases. Theta power decrease in Alzheimer patients within one or two weeks of rivastigmine treatment has been found to be related to therapeutic response, a strong theta decrease predicting a good therapeutic efficacy of rivastigmine. Little is known about the quantitative EEG effects of memantine, a noncompetitive NMDA receptor antagonist, which is also used for the treatment of Alzheimer’s disease. Objective(s): We conduct an ongoing study comparing the short-term EEG effects of rivastigmine and memantine in Alzheimer patients. Methods: An interim analysis was performed, using the data of 49 Alzheimer patients (NINCDS-ADRDA criteria), 15 men and 34 women at ages of 62 to 85 years (mean: 76 years). EEG was assessed prior to treatment initiation. Then, the patients were randomized in a 1:1 ratio to either treatment with rivastigmine (3 mg p.d.) or memantine (10 mg p.d.). After 2 weeks of treatment, a second EEG recording was performed. EEG data were quantitatively analyzed, calculating mean theta power and left temporal alpha coherence before and under treatment with either rivastigmine or memantine. Results: Mean theta power decreased under both treatments. However, theta decrease was only found significant under rivastigmine (from 34.4 ⫹ 23.4 V2 to 20.1 ⫹ 14.7 V2; df⫽23, t⫽3.908, p⫽0.001), not under memantine (from 30.1 ⫹ 30.6 V2 to 26.6 ⫹ 24.9 V2; df⫽24, t⫽1.388, p⫽0.178). Theta decrease was significantly stronger under rivastigmine than under memantine treatment (-14.3 ⫹ 17.8 V2 vs. -3.6 ⫹ 12.8 V2; df⫽47, t⫽-2.403, p⫽0.021). Left temporal alpha coherence remained unchanged under either treatment. Conclusions: Rivastigmine showed significant EEG effects, probably brought about by its cholinergic efficacy. We failed to demonstrate such effects in memantine, although they might be anticipated by vigilanceincreasing properties of this substance. P3-457
TREATMENT OF SEVERE ALZHEIMER’S DISEASE WITH DONEPEZIL: RESULTS FROM A 24-WEEK, PARALLEL, PLACEBO-CONTROLLED STUDY IN JAPAN
Akira Homma1, Itaru Arimoto2, Kasumi Daidoji2, Toshio Ohbayashi2, Hideo Ozawa3, 1Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan; 2Eisai Co., Ltd., Tokyo, Japan. Contact e-mail: [email protected] Background: Post-hoc analyses of donepezil treatment in more severe AD patients have demonstrated benefits in cognitive and functional measures. These results require substantiation in prospective, controlled trials with populations clinically defined as having severe AD. Objective(s): To determine donepezil’s efficacy and tolerability in severe Alzheimer’s disease (AD). Methods: Severe AD patients (MMSE scores, 1-12; MHI scores, 6; FAST scores 6) were enrolled in this parallel, double-blind, placebo-controlled study in 66 sites in Japan. Patients (n⫽325) were randomized to donepezil 5-mg (after 3mg/d for 2 weeks, n⫽110), donepezil 10-mg (after 3mg/d for 2 weeks followed by 5-mg/d for 4 weeks, n⫽103), or placebo (n⫽112) for 24 weeks. Twenty three patients withdrew from the study before administering study drugs. A total of 290 patients (n⫽96 in 5-mg, n⫽92 in 10-mg, 102 in placebo, respectively) were analyzed for efficacy. Statistical analyses were done on full analysis set last observation carried forward (FAS-LOCF) population and FAS observed case (FAS-OC) at Week 24 population. Primary outcome measures were change from baseline to endpoint (FAS-LOCF) in Severe Impairment
Poster P3:: Tuesday Posters
pected of having ongoing bacterial infection with Borrelia, long term antibiotic therapy (6 months) will be instituted along with 200 hrs of DC EMF therapy. A parallel trial of Alzheimer patients diagnosed with Lyme by ILADS criteria with 6 months of Doxycycline/ Tindazole without DC electromagnetic therapy is also planned.
P3-455
DONEPEZIL TREATMENT FOR ALZHEIMER’S DISEASE IN CHRONIC DIALYSIS PATIENTS
Konstantina G. Yiannopoulou, Athina K. Euthymiou, Kleanthis D. Karydakis, General Hospital of Athens, Athens, Greece. Contact e-mail: [email protected] Background: Donepezil is one of the cholinesterase inhibitors that are indicated for the treatment of mild to moderate Alzheimer’s Disease. Pharmacokinetic analysis has shown that donepezil is primarily eliminated by renal excretion rather than biliary excretion in humans. Therefore, patients with impaired renal function are at high risk for toxicity caused by accumulation of this drug. It is also well known that dialysis patients have very often cholinergic disorders. On the other hand, with the increasing number of long-term chronic dialysis patients, the prevalence of cognitive disorders is increasing in the elderly of them. Because of the above mentioned special risks, prescription of acetylocholinesterase inhibitors, such as donepezil, to be avoided is prescribed. There is only one study that evaluates the pharmacokinetics of donepezil in patients with impaired renal function and only one case-report with donepezil treatment in a chronic-dialysis patient. Objectives: This pilot study aimed to investigate whether there is a safe dose of donepezil to be administered in chronic dialysis patients with Alzheimer’s disease and if this treatment offers a possible benefit to them. Methods: We studied three cases of chronic hemodialysis outpatients (2 men and 1 woman, 72, 86 and 65 years old respectively), that were diagnosed as having moderate Alzheimer’s disease. Study subjects underwent a baseline clinical and laboratory assessment and a neuropsychological examination (including MMSE, GDS, NPI and IADL scale), that it was repeated every month. All patients were followed for 6 months. We began treatment with donepezil on the lower dose of 2.5mg/day orally and we enhanced the dose to 5mg/day one month later. Results: After 1 month’s treatment, they improved to a controllable psychiatric condition, without having any adverse effects. After 3 months of treatment with the higher dose, their cognitive and executive functions were slightly improved and their behavior was remarkably improved, without experiencing any episodes of drug toxicity. The patients’ condition remained stable for 6 months after the initial administration of the drug. Conclusion: Our cases indicate that donepezil treatment under prudent use may be well tolerated and have a beneficial impact on chronic hemodialysis patients with Alzheimer’s disease.
P3-456
DIFFERENTIAL QUANTITATIVE EEG EFFECTS OF RIVASTIGMINE AND MEMANTINE IN ALZHEIMER PATIENTS
Georg Adler1, Oliver Hennig1, Eva Grips1, Petra van Keulen2, Martin Roser2, Ferenc Tracik3, Lutz Froelich1, 1Central Institute of Mental Health, Mannheim, Germany; 2Psychiatrisches Zentrum Calw, Calw, Germany; 3Novartis GmbH, Nu¨rnberg, Germany. Contact e-mail: [email protected] Background: In the quantitative EEG of Alzheimer patients, mean theta power is increased and left temporal alpha coherence is decreased. Under treatment with the acetylcholine esterase inhibitor rivastigmine theta power decreases. Theta power decrease in Alzheimer patients within one or two weeks of rivastigmine treatment has been found to be related to therapeutic response, a strong theta decrease predicting a good therapeutic efficacy of rivastigmine. Little is known about the quantitative EEG effects of memantine, a noncompetitive NMDA receptor antagonist, which is also used for the treatment of Alzheimer’s disease. Objective(s): We conduct an ongoing study comparing the short-term EEG effects of rivastigmine and memantine in Alzheimer patients. Methods: An interim analysis was performed, using the data of 49 Alzheimer patients (NINCDS-ADRDA criteria), 15 men and 34 women at ages of 62 to 85 years (mean: 76 years). EEG was assessed prior to treatment initiation. Then, the patients were randomized in a 1:1 ratio to either treatment with rivastigmine (3 mg p.d.) or memantine (10 mg p.d.). After 2 weeks of treatment, a second EEG recording was performed. EEG data were quantitatively analyzed, calculating mean theta power and left temporal alpha coherence before and under treatment with either rivastigmine or memantine. Results: Mean theta power decreased under both treatments. However, theta decrease was only found significant under rivastigmine (from 34.4 ⫹ 23.4 V2 to 20.1 ⫹ 14.7 V2; df⫽23, t⫽3.908, p⫽0.001), not under memantine (from 30.1 ⫹ 30.6 V2 to 26.6 ⫹ 24.9 V2; df⫽24, t⫽1.388, p⫽0.178). Theta decrease was significantly stronger under rivastigmine than under memantine treatment (-14.3 ⫹ 17.8 V2 vs. -3.6 ⫹ 12.8 V2; df⫽47, t⫽-2.403, p⫽0.021). Left temporal alpha coherence remained unchanged under either treatment. Conclusions: Rivastigmine showed significant EEG effects, probably brought about by its cholinergic efficacy. We failed to demonstrate such effects in memantine, although they might be anticipated by vigilanceincreasing properties of this substance. P3-457
TREATMENT OF SEVERE ALZHEIMER’S DISEASE WITH DONEPEZIL: RESULTS FROM A 24-WEEK, PARALLEL, PLACEBO-CONTROLLED STUDY IN JAPAN
Akira Homma1, Itaru Arimoto2, Kasumi Daidoji2, Toshio Ohbayashi2, Hideo Ozawa3, 1Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan; 2Eisai Co., Ltd., Tokyo, Japan. Contact e-mail: [email protected] Background: Post-hoc analyses of donepezil treatment in more severe AD patients have demonstrated benefits in cognitive and functional measures. These results require substantiation in prospective, controlled trials with populations clinically defined as having severe AD. Objective(s): To determine donepezil’s efficacy and tolerability in severe Alzheimer’s disease (AD). Methods: Severe AD patients (MMSE scores, 1-12; MHI scores, 6; FAST scores 6) were enrolled in this parallel, double-blind, placebo-controlled study in 66 sites in Japan. Patients (n⫽325) were randomized to donepezil 5-mg (after 3mg/d for 2 weeks, n⫽110), donepezil 10-mg (after 3mg/d for 2 weeks followed by 5-mg/d for 4 weeks, n⫽103), or placebo (n⫽112) for 24 weeks. Twenty three patients withdrew from the study before administering study drugs. A total of 290 patients (n⫽96 in 5-mg, n⫽92 in 10-mg, 102 in placebo, respectively) were analyzed for efficacy. Statistical analyses were done on full analysis set last observation carried forward (FAS-LOCF) population and FAS observed case (FAS-OC) at Week 24 population. Primary outcome measures were change from baseline to endpoint (FAS-LOCF) in Severe Impairment