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Impairments of social cognition and decision making in Alzheimer disease
S28
@zJ
Poster
IMPAIRMENTS
OF SOCIAL
ING IN ALZHEIMER
COGNITION
AND DECISION
MAK-
DISEASE
Janus L Kwner. Twxsu Torralva, Flnvia Dorrego, L&ma Suhr, Roul Currtw Institute of Neurologicul Rrseurch FLENI, Buenos Aires Argmtinrr; Eran Chemrrinski, Univ of Iowa, Iowa. IA Argentina; Esteban Fridman, Raul Carrea Institute of Neurologicul Research FLENI, Buenos Aires Argentinn Objective: To investigate the nature of deficits m social cognition and real-life decision-making in a group of patients wth Alzheimer direase (AD). Design: A comprehensive neuropsychological and psychiatric assessment, including the Moral Judgment Interview and the Bechara’s Card TeFt, was carried out in 25 patients with AD and 20 age-comparable normal controls. Results: AD patients obtained significantly lower scores on the Moral Judgment Interview and obtained significantly less earnings on the card test when compared to the normal control group. The Moral Judgment Interview score correlated significantly with Raven’s Progressive Matrices and Block Design, whereaa the Card Test correlated significantly with both the Benton Vicual Retention Test and the Buschke Selective Reminding Test. No significant correlations were observed between the experimental tasks and psychiatric variables such as irritability. apathy. depression, and delusions. Conclusions: AD patients demonstrated significant deficits on tasks assessing social cognition and real-life decision-making, These impairments correlated with deficits on tasks of abstract reasoning, constructional praxis. and memory, but not with behavioral problems frequently found in AD patients.
SPECIFICITY
OF DEPRESSIVE
SYMPTOMS
IN ALZHEIMER’S
Presentation:
Clinicul
Research
lysin five days per week for four weeks. Effects on cognition and global function were evaluated with the Alzheimer Disease Assessment Scale-Cognitive Subscale (ADASCog) and the Clinicians Interview-based Impression of Change with Caregiver Input wzale (CIBIC+) 4, 12, 24 weeks after the beginning of the injections. Results: A total of 192 patients were enrolled, 95 were randomized to Placebo, and 97 to Cerebrolyain. At baseline, there was a significant difference between groups for age, age of onset of dementia, and the number of patients with hallucinations. No group differences for change5 in the ADAS-Cog were detected at any time. However, there was a significant difference on the CIBlC+ (p=O.O33) in favor of Cerebrolysin at week 12. The number of CIBIC+ responders (score 5 4), was significantly higher (p=O.o07), with 68 (76%) in the Cerebrolysin group and 5 I (57%) in the Placebo group. Trends were noted in the Disability Assessment in Dementia scale and the Cornell Depression Scale. Adverse events were recorded in 73% of Placebo and 64% of Cerebrolysm patients. Most common adverse events were headaches, dizziness, weight lob\ and anxiety. Conclusions: Cerebrolysin treatment was well tolerated and resulted in significant improvements in the global score two months after the end of active treatment. Further experiments are warranted to explore the neurotrophic effect of Cerebrolysin in AD.
MAD-B STUDY: 11291THE CEBO-CONTROLLED HEIMER’S
A RANDOMIZED, TRIAL
WITH
DOUBLE-BLIND, CEREBROLYSIN
PLAIN ALZ-
DISEASE
Eckhart Ruether. Univ of Goettingm. Gorttingm Gurmany; Herbert Moe.nlrr. EBEWE Arzneimittrl GmbH, Untrrach Austria; Manfred Wind&h, JSW-Research. Gra: Austria
DISEASE
Sergio E Sturkstein, Raul Carrea Institute qfNeurologicn1 Research - FLENI, Buenos Aires Argentina; Eran Chemerins k’ I, Univ of Iowa. Iowa, IA Argentina: Gu.strwo Petmcca, Lilinno &be, Ruul Carreu lmtrtute of Neurological Research FLENI, Buenos Aires Argentina Objective: To awx the specificity of depressive symptoms in Alzheimer’s disease (AD), and examine discrepancies between patients and caregivers reports. Background: Whereas depression is a frequent finding in AD. few studies have examined the specificity of depressive symptoms in this disorder, and concordance among informants. Methods: Our sample included B series of 233 patients with AD, 47 patients with depression but no dementia comparable in age with the AD group, and 20 age-comparable normal controls. Patients and controls received a comprehensive psychiatric evaluation, which included the Hamilton Depression Scale (HAM-D) and the Structured Clinical Interview for DSM-IV (KID). Reaulth: AD patients with a score > 2 on item 1 of the HAM-D (“depressed mood”) as scored by their respective caregivers, were included into a depressed mood group (n=92), whereas patients xoring 0 on this item were included in a non-depressed mood group (n=62). A statistical comparison for the remaining HAM-D items between AD patients with or without depressed mood showed significant difference\ for all the items, except for IOFEof appetite and loss of weight. On the other hand, there were no significant differences on any single HAM-D item between AD patients without depressed mood and age-comparable normal controls. Depressed patients without AD showed significantly more severe suicidal ideation, somatic anxiety, loss of appetite, and loss of weight, but significantly leas psychomotor retardation than AD patients with depressed mood. Only one of the 62 AD patients without depressed mood (1.6%) had enough depressive symptoms (except for depressed mood or loss of interest) to meet DSM-IV criteria for major depression (i.e., a “marked” depression). Finally, AD patienta with depressed mood significantly under-reported the frequency of, insomnia. psychomotor retardation, loss of interest, loss of energy, hypochondriaaia, loss of libido, and loss of weight. Conclusions: Deprewve symptoms are not widespread among patients with AD, but are significantly related to an underlying depressed mood. AD pattents may not be fully ware of the extent of their deprcasivr symptoms.
TREATMENT
OF
ALZHEIMER’S
DISEASE:
DOUBLE-BLIND,
PLACEBO-CONTROLLED
NEUROTROPHIC
AGENT
A RANDOMIZED, TRIAL
WITH
A
Michel Puni.net, Serge Gouthirr. McGill Crrfor Study on Aging, Montreul Cunadw Herbert Mor.ss/er. EBEWE Armrirnitte4 GmbH, Unternch Austria: Manfred Windisch. .JSW-Rrwarch. Gro: Austriu Objrctiw: Cerebrolysin is a compound with nrurotrophic activity. It ia produced by a standardised enzymatic cleavage of purified bran proteins and consist, of low molecular weight peptides and free amino acids. Cerehrolyain has been shown to be effective m the treatment of Alrheimer’s disease (AD) in earher small trials. The aim of this study was to evaluate the efficacy and tolerability of Cerebrolysin in patient\ with AD. Design: Multlcenter, randomixd. double-blind. placebo-controlled. parallel-group study. Patients were mlected intravenowly wth Placebo or 3OmL Ccrebro-
Objective. Cerebrolysin is a peptide preparation with neurotrophic activity. It consists of low molecular weigth peptides and free amino acids. In earlier clinical trials, it has been shown to be effective in the treatment of Alzheimer’s disease (AD) after only one month of active therapy. In the present study, the effects of repeated treatments with Cerebrolysin were investigated in patients with AD. Methods. Multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Patients were injected IV with Placebo OI 30mL Cerebrolysin on five days per week for four weeks. Treatment WBFrepeated after a two-month therapy-free interval. Effects on cognition and global function were evaluated with the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and the Clinical Global Impressions (CGI) 4, 16 (primary study endpoint), and 2X weeka after the beginning of the injections. Results. Of 147 patients enrolled, 71 were randomized to Placebo, and 76 to CERE. A statistically significant group difference was observed at week 16 for the CC1 (p
FLUID
DIAGNOSIS
PROTEIN
TAU
OF ALZHEIMER’S
LEVELS
IN THE
DIF-
DISEASE
Peter Schornknrcht, Johannrs Schroeder, Johunnes Pantel, Section of Geriatric P.sychiutry. Univ of Heidelberg, Heidelberg Germany: Egorr We&, Univ of Hcidelberg, Hridelbrrg Germmy; Tobius Hartmann, Ctr fix Moleculur Biology (ZMBH). Heidelberg Grrmony; Marco Esssig, Klaus Baudendistel. German Cancer Research Cn; Heidelberg Germuny; Konrud Bryreuthrr, Ctrfor Molrrular Biology (ZMBH), Hridelberg Germany Tau protein concentration in cerebrospinal fluid was determined in 55 patients with Alzheimer’s disease (AD), IX patient< with vascular dementia (VD), 19 patients with dementia caused by other disorders and 14 patienta with late life depression. Significantly (piO.05) elevated protein tau concentrations were found in AD patients (564.5 2 275.5 pg/ml) compared with all other patient groups (VD: 406.5 + 263.9 pg/mI: other dementia: 275.0 -t 135.4 pg/mI: depression: 212.9 ? 115.6 pg/ml). However, tau levels in AD patient5 covered a broad range (163.2 pg/ml 1200 pg/ml). The AD patients with tau levels below the 25%.percentile of the distribution (among them a high percentage of patientr with presenilc onset) showed tau levels similar to those of the patient, with late life depression. No Tignificant correlation between tau level\ and clinical variables such as severity of dementia, age. age of oncct. duratmn of ~llnee. and cerebral change\ a\ awssed by volumetric magnetic resonance
@zJ
Poster
IMPAIRMENTS
OF SOCIAL
ING IN ALZHEIMER
COGNITION
AND DECISION
MAK-
DISEASE
Janus L Kwner. Twxsu Torralva, Flnvia Dorrego, L&ma Suhr, Roul Currtw Institute of Neurologicul Rrseurch FLENI, Buenos Aires Argmtinrr; Eran Chemrrinski, Univ of Iowa, Iowa. IA Argentina; Esteban Fridman, Raul Carrea Institute of Neurologicul Research FLENI, Buenos Aires Argentinn Objective: To investigate the nature of deficits m social cognition and real-life decision-making in a group of patients wth Alzheimer direase (AD). Design: A comprehensive neuropsychological and psychiatric assessment, including the Moral Judgment Interview and the Bechara’s Card TeFt, was carried out in 25 patients with AD and 20 age-comparable normal controls. Results: AD patients obtained significantly lower scores on the Moral Judgment Interview and obtained significantly less earnings on the card test when compared to the normal control group. The Moral Judgment Interview score correlated significantly with Raven’s Progressive Matrices and Block Design, whereaa the Card Test correlated significantly with both the Benton Vicual Retention Test and the Buschke Selective Reminding Test. No significant correlations were observed between the experimental tasks and psychiatric variables such as irritability. apathy. depression, and delusions. Conclusions: AD patients demonstrated significant deficits on tasks assessing social cognition and real-life decision-making, These impairments correlated with deficits on tasks of abstract reasoning, constructional praxis. and memory, but not with behavioral problems frequently found in AD patients.
SPECIFICITY
OF DEPRESSIVE
SYMPTOMS
IN ALZHEIMER’S
Presentation:
Clinicul
Research
lysin five days per week for four weeks. Effects on cognition and global function were evaluated with the Alzheimer Disease Assessment Scale-Cognitive Subscale (ADASCog) and the Clinicians Interview-based Impression of Change with Caregiver Input wzale (CIBIC+) 4, 12, 24 weeks after the beginning of the injections. Results: A total of 192 patients were enrolled, 95 were randomized to Placebo, and 97 to Cerebrolyain. At baseline, there was a significant difference between groups for age, age of onset of dementia, and the number of patients with hallucinations. No group differences for change5 in the ADAS-Cog were detected at any time. However, there was a significant difference on the CIBlC+ (p=O.O33) in favor of Cerebrolysin at week 12. The number of CIBIC+ responders (score 5 4), was significantly higher (p=O.o07), with 68 (76%) in the Cerebrolysin group and 5 I (57%) in the Placebo group. Trends were noted in the Disability Assessment in Dementia scale and the Cornell Depression Scale. Adverse events were recorded in 73% of Placebo and 64% of Cerebrolysm patients. Most common adverse events were headaches, dizziness, weight lob\ and anxiety. Conclusions: Cerebrolysin treatment was well tolerated and resulted in significant improvements in the global score two months after the end of active treatment. Further experiments are warranted to explore the neurotrophic effect of Cerebrolysin in AD.
MAD-B STUDY: 11291THE CEBO-CONTROLLED HEIMER’S
A RANDOMIZED, TRIAL
WITH
DOUBLE-BLIND, CEREBROLYSIN
PLAIN ALZ-
DISEASE
Eckhart Ruether. Univ of Goettingm. Gorttingm Gurmany; Herbert Moe.nlrr. EBEWE Arzneimittrl GmbH, Untrrach Austria; Manfred Wind&h, JSW-Research. Gra: Austria
DISEASE
Sergio E Sturkstein, Raul Carrea Institute qfNeurologicn1 Research - FLENI, Buenos Aires Argentina; Eran Chemerins k’ I, Univ of Iowa. Iowa, IA Argentina: Gu.strwo Petmcca, Lilinno &be, Ruul Carreu lmtrtute of Neurological Research FLENI, Buenos Aires Argentina Objective: To awx the specificity of depressive symptoms in Alzheimer’s disease (AD), and examine discrepancies between patients and caregivers reports. Background: Whereas depression is a frequent finding in AD. few studies have examined the specificity of depressive symptoms in this disorder, and concordance among informants. Methods: Our sample included B series of 233 patients with AD, 47 patients with depression but no dementia comparable in age with the AD group, and 20 age-comparable normal controls. Patients and controls received a comprehensive psychiatric evaluation, which included the Hamilton Depression Scale (HAM-D) and the Structured Clinical Interview for DSM-IV (KID). Reaulth: AD patients with a score > 2 on item 1 of the HAM-D (“depressed mood”) as scored by their respective caregivers, were included into a depressed mood group (n=92), whereas patients xoring 0 on this item were included in a non-depressed mood group (n=62). A statistical comparison for the remaining HAM-D items between AD patients with or without depressed mood showed significant difference\ for all the items, except for IOFEof appetite and loss of weight. On the other hand, there were no significant differences on any single HAM-D item between AD patients without depressed mood and age-comparable normal controls. Depressed patients without AD showed significantly more severe suicidal ideation, somatic anxiety, loss of appetite, and loss of weight, but significantly leas psychomotor retardation than AD patients with depressed mood. Only one of the 62 AD patients without depressed mood (1.6%) had enough depressive symptoms (except for depressed mood or loss of interest) to meet DSM-IV criteria for major depression (i.e., a “marked” depression). Finally, AD patienta with depressed mood significantly under-reported the frequency of, insomnia. psychomotor retardation, loss of interest, loss of energy, hypochondriaaia, loss of libido, and loss of weight. Conclusions: Deprewve symptoms are not widespread among patients with AD, but are significantly related to an underlying depressed mood. AD pattents may not be fully ware of the extent of their deprcasivr symptoms.
TREATMENT
OF
ALZHEIMER’S
DISEASE:
DOUBLE-BLIND,
PLACEBO-CONTROLLED
NEUROTROPHIC
AGENT
A RANDOMIZED, TRIAL
WITH
A
Michel Puni.net, Serge Gouthirr. McGill Crrfor Study on Aging, Montreul Cunadw Herbert Mor.ss/er. EBEWE Armrirnitte4 GmbH, Unternch Austria: Manfred Windisch. .JSW-Rrwarch. Gro: Austriu Objrctiw: Cerebrolysin is a compound with nrurotrophic activity. It ia produced by a standardised enzymatic cleavage of purified bran proteins and consist, of low molecular weight peptides and free amino acids. Cerehrolyain has been shown to be effective m the treatment of Alrheimer’s disease (AD) in earher small trials. The aim of this study was to evaluate the efficacy and tolerability of Cerebrolysin in patient\ with AD. Design: Multlcenter, randomixd. double-blind. placebo-controlled. parallel-group study. Patients were mlected intravenowly wth Placebo or 3OmL Ccrebro-
Objective. Cerebrolysin is a peptide preparation with neurotrophic activity. It consists of low molecular weigth peptides and free amino acids. In earlier clinical trials, it has been shown to be effective in the treatment of Alzheimer’s disease (AD) after only one month of active therapy. In the present study, the effects of repeated treatments with Cerebrolysin were investigated in patients with AD. Methods. Multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Patients were injected IV with Placebo OI 30mL Cerebrolysin on five days per week for four weeks. Treatment WBFrepeated after a two-month therapy-free interval. Effects on cognition and global function were evaluated with the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and the Clinical Global Impressions (CGI) 4, 16 (primary study endpoint), and 2X weeka after the beginning of the injections. Results. Of 147 patients enrolled, 71 were randomized to Placebo, and 76 to CERE. A statistically significant group difference was observed at week 16 for the CC1 (p
FLUID
DIAGNOSIS
PROTEIN
TAU
OF ALZHEIMER’S
LEVELS
IN THE
DIF-
DISEASE
Peter Schornknrcht, Johannrs Schroeder, Johunnes Pantel, Section of Geriatric P.sychiutry. Univ of Heidelberg, Heidelberg Germany: Egorr We&, Univ of Hcidelberg, Hridelbrrg Germmy; Tobius Hartmann, Ctr fix Moleculur Biology (ZMBH). Heidelberg Grrmony; Marco Esssig, Klaus Baudendistel. German Cancer Research Cn; Heidelberg Germuny; Konrud Bryreuthrr, Ctrfor Molrrular Biology (ZMBH), Hridelberg Germany Tau protein concentration in cerebrospinal fluid was determined in 55 patients with Alzheimer’s disease (AD), IX patient< with vascular dementia (VD), 19 patients with dementia caused by other disorders and 14 patienta with late life depression. Significantly (piO.05) elevated protein tau concentrations were found in AD patients (564.5 2 275.5 pg/ml) compared with all other patient groups (VD: 406.5 + 263.9 pg/mI: other dementia: 275.0 -t 135.4 pg/mI: depression: 212.9 ? 115.6 pg/ml). However, tau levels in AD patient5 covered a broad range (163.2 pg/ml 1200 pg/ml). The AD patients with tau levels below the 25%.percentile of the distribution (among them a high percentage of patientr with presenilc onset) showed tau levels similar to those of the patient, with late life depression. No Tignificant correlation between tau level\ and clinical variables such as severity of dementia, age. age of oncct. duratmn of ~llnee. and cerebral change\ a\ awssed by volumetric magnetic resonance