- Email: [email protected]
The Sydney Memory and Ageing Study (MAS): A population-based longitudinal investigation of cognitive health in the elderly
P290
Poster Presentations P2
University School of Medicine, Suwon, Republic of Korea; 6Sungkyunkwan University School of Medicine, Suwon, Republic of Korea; 7MunGyeong Jeil Hospital, Mungyeong-si, Republic of Korea; 8Konkuk University School of Medicine, Seoul, Republic of Korea; 9Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Republic of Korea. Contact e-mail: [email protected] Background: Considerable proportion of Alzheimer’s disease (AD) subjects show white matter(WM) ischemic changes on MRI of which the clinical significance is controversial. On the other hand, the subcortical ischemic vascular dementia (SVaD) patients typically exhibit varying degree of ischemic changes on MRI but the progress of dementia syndrome is slow and progressive, thus making it difficult to differentiate with AD. To clarify the relationship among the cognitive impairment, functional impairment, and WM ischemia on MRI, the authors recruited subjects with cognitive impairment, and re-classified them into 12 cell matrix that consisted of four cognition levels (normal, cognitively impaired, dementic, severely dementic) and three MRI ischemia severities (minimal, moderate, severe). The purpose of this classification is to elucidate the demographic and clinical characteristics of cognitively impaired (CI) subjects according to their level of cognitive impairment and the severity of WM ischemia. Here we report the basic features of this CREDOS (Clinical REsearch of Dementia Of South korea) dataset, so-called ‘‘12 Cell Diagnostic Matrix System.’’ Methods: Using common protocol for dementia assessment, 33 dementia clinic centers in South Korea recruited subjects with cognitive disorders with or without small vessel disease, evidenced by ischemic changes on MRI. By registering on the internet based database, the authors recruited 7,129 subjects with cognitive disorders. Final 2,826 cogntively impaired subjects irrespective of their MRI ischemia lesion were analyzed. Results: About half of the subjects (1,466; 51.9%) were mild to moderate dementia, of which the ischemia severity distribution were 9:3:2. For the cognitively impaired group, the ischemia severity distribution was 7:2:1. Mean age for the subjects was 74.4 þ/- 6.7, and the female ratio was two-fold. Education level 7.2 years for dementia with minimal ischemia, but 5.5 years for dementia with severe ischemic change on MRI. Conclusions: This study integrated cognitive impairment and white matter ischemic changes of dementia patients into newly-developed diagnostic system and revealed the clinical characteristics of the cohort, including demographic data, clinical features, co-morbidity, neuropsychological performance, neuropsychiatric symptoms, functional impairment. The CREDOS study will allow a detailed study of the longitudinal course of dementia.
P2-096
POLYMORPHISM OF GLUTATHIONE-STRANSFERASE (GSTM1 AND T1) IN DEMENTIA OF ALZHEIMER’S TYPE IN NORTH INDIAN POPULATION: A PRELIMINARY STUDY
Tandra Ghosh, Vivek Kumar, M. D. Mustafa, Sudip Dutta, B. D. Banerjee, M. S. Bhatia, S. S. Sircar, University College of Medical Sciences & GTBH, Delhi, India. Contact e-mail: [email protected]
Background: Alzheimer disease (AD) is the most common form of dementia. Risk factors include strong genetic component that involves gene-environment interaction also. Recent studies have focused on the role of oxidative stress and neuronal death in AD. Thus, the role of antioxidant glutathione S-transferase (GST) isoenzymes as risk factors for AD could be important. Reduced GST activity has been reported in multiple brain regions and in ventricular cerebrospinal fluid AD patients. Furthermore, there are no published data about the role of GST genotype polymorphisms, such as GSTT1 and GSTM1 on the susceptibility for AD in Indian population. GST M1 and GSTT1 both may be deleted completely and null genotype is associated with decreased enzymatic activity. The aim of our study was to determine the GSTM1 (homozygous deletion vs. non-deleted), and GSTT1 (homozygous deletion vs. nondeleted), polymorphisms in AD, to clarify their role as candidate genes. Methods: We included 60 AD patients {based on Hindi Mental State Examination (HMSE) and Clinical Dementia Rating (CDR) }scale from psychiatry and neurology OPD of Guru Teg Bahadur Hospital, New Delhi and 60 healthy controls matched for age, sex, and educational level for our preliminary case-control genetic association study. GSTM1 and GSTT1 genotypes were studied by multiplex PCR followed by gel documentation. Data was analyzed by logistic regression after age and sex matching. Odds ratio (OR) and 95% confidence interval (CI) was also calculated for combination of genotypes (both the gene present, both absent, either of them absent). Results: Deletion of GSTT1 (OR¼0.48, 95% CI: 0.17-1.37, p¼0.17) genotype was found 37% of cases in comparison to 22% in controls and GSTM1 (OR¼0.53, 95% CI: 0.201.37, p¼0.19) genotype was deleted in 54% cases compared to 39% in controls. Deletion of both GSTT1 and GSTM1 (OR¼ 2.96, 95% CI: 0.72-10.57, p¼0.04) genotype was found in 23% of cases than 13% in controls. Conclusions: Taken together, these results do not give evidence for association with either GSTM1 or GSTT1. However, greater degree of deletion of both GSTT1 and GSTM1 genotype may be a risk factor for AD. Study with a larger sample size is further required to address these uncertainties. P2-097
THE SYDNEY MEMORY AND AGEING STUDY (MAS): A POPULATION-BASED LONGITUDINAL INVESTIGATION OF COGNITIVE HEALTH IN THE ELDERLY
Nicole Kochan1, Henry Brodaty1,2, Julian Trollor1, Brian Draper1, Wei Wen1, Melissa Slavin1, Simone Reppermund1, John Crawford1, Kristan Kang1, G. A. (Tony) Broe3, Peter Schofield3, Perminder Sachdev1, 1 University of New South Wales, Sydney, Australia; 2Dementia Collaborative Research Centre, Sydney, Australia; 3Prince of Wales Medical Research Institute, Sydney, Australia. Contact e-mail: [email protected] Background: The Sydney Memory and Ageing Study (MAS) is a population-based longitudinal study of nondemented older individuals. The study aims to advance knowledge of causes, risk factors and protective factors, of neurocognitive disorders in the elderly by incorporating comprehensive and multidimensional investigations including neuroimaging and potential biomarkers. A second aim is to refine criteria for early diagnosis of prodromal stages of dementia. Methods: From 2005, 1037 community-dwelling persons, aged 70-90, were recruited randomly from the Australian Electoral Roll. At wave 1, participants received a comprehensive assessment: clinical examination, physical assessments (eg spirometry, balance), traditional and computerized neuropsychological assessments, donation of blood sample for biochemistry and DNA extraction/development of immortalized cell lines, proteomics, neuroimaging incorporating structural MRI, diffusion tensor imaging, susceptibility-weighted imaging and, for a subgroup, functional MRI protocol examining cortical responses to increasing cognitive challenge. Questionnaires regarding nutrition, current and previous levels of physical, cognitive and social activity and service utilization are collected and disease burden is calculated. Informants provide data on participants’ functional abilities and neuropsychiatric status. Participants receive a brief telephone assessment at 12 and 36-months and repeat comprehensive assessment every second year. Results: Wave 1 data collection was completed late 2007 and approximately half the
Poster Presentations P2 group have been seen for Wave 2. Cross-sectional data have raised interesting questions about the validity of current MCI diagnostic criteria. Over 95% of participants and/or their informants affirmed at least one of the questions about decline in memory and/or other cognitive abilities, calling into question the utility of the subjective complaints criterion. We have also highlighted the problems inherent in defining cognitive impairment for the MCI criteria and the considerable variability in prevalence depending on methods used to operationalize cognitive impairment. Early neuroimaging results, using the new DARTEL method of voxel-based morphometry (VBM) to evaluate the relationship between grey matter volume and verbal fluency performance, and the ability of DTI measures to reliably discriminate individuals with MCI from healthy elderly, are promising. Conclusions: The Memory and Ageing Study provides a large comprehensively assessed cohort with clinical, psychological, functional and biometric data, which will be a valuable resource for collaborative research on cognitive disorders in the elderly. P2-098
VERBAL FLUENCY AND PHYSICAL ACTIVITY IN THE AGING PROCESS: AN EPIDEMIOLOGICAL ˜ O PAULO, BRAZIL STUDY CARRIED OUT IN SA
Thais B. L. da Silva1, Moˆnica S. Yassuda2, 1University of Sa˜o Paulo, Sa˜o Paulo, Brazil; 2University of Sa˜o Paulo, Sa˜o Paulo, Brazil, Brazil. Contact e-mail: [email protected] Background: Studies have documented significant decline among the elderly in some cognitive abilities, including the executive functions associated with the ability to plan, monitor, organize, sort, among others. The verbal fluency test animal category has been considered an important measure of preservation of executive functions. To study the association between physical activity and cognition, by correlating performance on the verbal fluency test variables to the level of physical activity of participants, and socio-demographic variables among elderly residents in Ermelino Matarazzo, a poor district of Sa˜o Paulo city. Methods: 383 elderly (60 years and over) participated in a cross-sectional study which used epidemiological methodology. Physical activity was assessed by the IPAQ (International Physical Activity Questionnaire) and the VIGITEL questionnaire (Surveillance of Risk Factors for Chronic Diseases through Telephone Interviews). Cognition was assessed by the verbal fluency animal category test. Results: The performance in verbal fluency was compared among the elderly who were active and inactive in locomotion, walking and leisure. There was superior performance for the active elderly, however, the difference between the groups only approached and the statistical significance for locomotion and walking. There was significant difference between the active and inactive groups for the number of animals spoken in the first 15 seconds, suggesting that active seniors are faster in semantic search. Performance was higher among men, among younger elderly (60-69 years) and among older people with five or more years of schooling. Conclusions: Active lifestyle may influence cognitive performance. P2-099
EARLY WINDOW OF MORTALITY RISK ON 3XTGAD MICE TREATED WITH AN ANTIPSYCHOTIC DRUG AT ADVANCED STAGES OF THE DISEASE
Lydia Gimenez Llort1, Helga Rivas1, Xe`nia Planas-Pujol2, Josep GarreOlmo2, Frank M. Laferla3, Joan Vilalta-Franch4, Secundı´ Lopez-Pousa4, 1 Dept of Psychiatry & Forensic Medicine, Institute of Neurosciences, Autonomous University of Barcelona, Bellaterra, Barcelona, Spain; 2Research Unit. Hospital de Sta Caterina, Institut d’Assiste`ncia Sanita`ria, Salt, Girona, Spain; 3Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA; 4Memory and Dementia Assessment Unit (UVAMID), Hospital de Sta Caterina, Institut d’Assiste`ncia Sanita`ria, Salt, Girona, Spain. Contact e-mail: [email protected] Background: Psychosis, aggression, and agitation are common problems in patients with dementia, and when severe or persistent, can cause considerable patient distress and disability, as well as caregiver strain and early
P291
institutionalization. In April 2005, the FDA determined that atypical antipsychotics were associated with a significantly greater mortality risk compared to placebo which prompted the addition of an FDA black-box warning regarding this risk. Now, the ACNP White Paper (2008) has reviewed this relevant issue and made clinical and research recommendations regarding the use of antipsychotics in elderly dementia patients with psychosis and/or agitation. In a recent retrospective work, we have confirmed the increase of mortality risk in patients at advanced ages of the disease who received risperidone therapy but we could not find any relationship to metabolic syndrome nor history of heart disease. Now, we are studying and monitoring the putative effects of etiological factors in 3xTgAD mice (harbouring PS1M146V, APPSwe, tauP301L) receiving a low dose of risperidone at advanced stages of the disease. Methods: Cognitive, BPSDlike symptoms and IPGTT of 12 month-old (bA neuropathological stage) male adult 3xTgAD and NonTg mice were evaluated before the start of treatment. Thereafter, half of the 3xTgAD mice were daily treated with a low dose of risperidone. Behavior and survival curves were recorded thought the experiment till very advances stages of the disease (both bA and tau pathologies). Results: We have found a clear risk mortality window close to the start of the treatment. The treated animals did not get much benefits of risperidone neither at cognitive nor BPSD-like symptoms and long-term survival was also shorter as compared to saline-treated 3xTgAD and NTg mice Conclusions: We have replicated the increased mortality risk on 3xTgAD mice. Therefore this animal model can be very useful to study the physiopathogenic factors involved in this subject of considerable public health significance. This early window of increased risk mortality fits with that described also for cerebrovascular adverse events in elderly users of antipsychotics what helps to delimitate a critical time window for critical causal events. Work supported by SAF200613642,UVAMID.
P2-100
COGNITIVE LEISURE ACTIVITY AS A PROTECTIVE FACTOR IN A PROSPECTIVE AGEING STUDY IN GERMANY
Christine Sattler, Pablo Toro, Johannes Schro¨der, University of Heidelberg, Heidelberg, Germany. Contact e-mail: christine.sattler@med. uni-heidelberg.de Background: Growing epidemiological evidence suggests that premorbid participation in cognitive leisure activities reduces the risk of dementia. We investigated if this protective effect was present in the populationbased Interdisciplinary Longitudinal Study on Adult Development and Aging (ILSE) and thus modulated the risk for developing either mild cognitive impairment (MCI) or Alzheimer’s disease (AD) in a representative birth cohort born between 1930 and 1932. The investigation of a representative birth cohort offers decisive advantages, such as an exclusion of age effects and age-related cohort effects. Methods: 500 participants of the ILSE-study were examined in 1993/94 (t1), 1997/98 (t2) and 2005/07 (t3). Participants were carefully screened for physical and mental health trough extensive medical interviews as well as physical and neuropsychological examinations throughout all examination waves. In addition the participants were asked to fill out a questionnaire concerning their current frequency of participation in cognitive and other leisure activities (e. g. reading, solving crossword puzzles). Participants were categorized as highly, moderately or poorly cognitively active according to their questionnaire statements. Results: 381 participants of the original cohort were re-examined at t3. Prevalence of MCI increased from 13 % to 23 % and 29 % over time. In addition 7 % of the participants developed AD at t3. Subjects who were highly cognitively active at t1 showed a reduced risk of developing MCI or AD in the 13-year follow-up period compared to healthy controls (OR¼0.23, 95 % CI 0.06-0.81, p<0.05 - scores adjusted for education and household income). Conclusions: Our results confirm the hypothesis that a high level of premorbid cognitive activity constitutes a protective factor for the development of MCI and AD. This effect remains significant after adjustment for education and household income.
Poster Presentations P2
University School of Medicine, Suwon, Republic of Korea; 6Sungkyunkwan University School of Medicine, Suwon, Republic of Korea; 7MunGyeong Jeil Hospital, Mungyeong-si, Republic of Korea; 8Konkuk University School of Medicine, Seoul, Republic of Korea; 9Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Republic of Korea. Contact e-mail: [email protected] Background: Considerable proportion of Alzheimer’s disease (AD) subjects show white matter(WM) ischemic changes on MRI of which the clinical significance is controversial. On the other hand, the subcortical ischemic vascular dementia (SVaD) patients typically exhibit varying degree of ischemic changes on MRI but the progress of dementia syndrome is slow and progressive, thus making it difficult to differentiate with AD. To clarify the relationship among the cognitive impairment, functional impairment, and WM ischemia on MRI, the authors recruited subjects with cognitive impairment, and re-classified them into 12 cell matrix that consisted of four cognition levels (normal, cognitively impaired, dementic, severely dementic) and three MRI ischemia severities (minimal, moderate, severe). The purpose of this classification is to elucidate the demographic and clinical characteristics of cognitively impaired (CI) subjects according to their level of cognitive impairment and the severity of WM ischemia. Here we report the basic features of this CREDOS (Clinical REsearch of Dementia Of South korea) dataset, so-called ‘‘12 Cell Diagnostic Matrix System.’’ Methods: Using common protocol for dementia assessment, 33 dementia clinic centers in South Korea recruited subjects with cognitive disorders with or without small vessel disease, evidenced by ischemic changes on MRI. By registering on the internet based database, the authors recruited 7,129 subjects with cognitive disorders. Final 2,826 cogntively impaired subjects irrespective of their MRI ischemia lesion were analyzed. Results: About half of the subjects (1,466; 51.9%) were mild to moderate dementia, of which the ischemia severity distribution were 9:3:2. For the cognitively impaired group, the ischemia severity distribution was 7:2:1. Mean age for the subjects was 74.4 þ/- 6.7, and the female ratio was two-fold. Education level 7.2 years for dementia with minimal ischemia, but 5.5 years for dementia with severe ischemic change on MRI. Conclusions: This study integrated cognitive impairment and white matter ischemic changes of dementia patients into newly-developed diagnostic system and revealed the clinical characteristics of the cohort, including demographic data, clinical features, co-morbidity, neuropsychological performance, neuropsychiatric symptoms, functional impairment. The CREDOS study will allow a detailed study of the longitudinal course of dementia.
P2-096
POLYMORPHISM OF GLUTATHIONE-STRANSFERASE (GSTM1 AND T1) IN DEMENTIA OF ALZHEIMER’S TYPE IN NORTH INDIAN POPULATION: A PRELIMINARY STUDY
Tandra Ghosh, Vivek Kumar, M. D. Mustafa, Sudip Dutta, B. D. Banerjee, M. S. Bhatia, S. S. Sircar, University College of Medical Sciences & GTBH, Delhi, India. Contact e-mail: [email protected]
Background: Alzheimer disease (AD) is the most common form of dementia. Risk factors include strong genetic component that involves gene-environment interaction also. Recent studies have focused on the role of oxidative stress and neuronal death in AD. Thus, the role of antioxidant glutathione S-transferase (GST) isoenzymes as risk factors for AD could be important. Reduced GST activity has been reported in multiple brain regions and in ventricular cerebrospinal fluid AD patients. Furthermore, there are no published data about the role of GST genotype polymorphisms, such as GSTT1 and GSTM1 on the susceptibility for AD in Indian population. GST M1 and GSTT1 both may be deleted completely and null genotype is associated with decreased enzymatic activity. The aim of our study was to determine the GSTM1 (homozygous deletion vs. non-deleted), and GSTT1 (homozygous deletion vs. nondeleted), polymorphisms in AD, to clarify their role as candidate genes. Methods: We included 60 AD patients {based on Hindi Mental State Examination (HMSE) and Clinical Dementia Rating (CDR) }scale from psychiatry and neurology OPD of Guru Teg Bahadur Hospital, New Delhi and 60 healthy controls matched for age, sex, and educational level for our preliminary case-control genetic association study. GSTM1 and GSTT1 genotypes were studied by multiplex PCR followed by gel documentation. Data was analyzed by logistic regression after age and sex matching. Odds ratio (OR) and 95% confidence interval (CI) was also calculated for combination of genotypes (both the gene present, both absent, either of them absent). Results: Deletion of GSTT1 (OR¼0.48, 95% CI: 0.17-1.37, p¼0.17) genotype was found 37% of cases in comparison to 22% in controls and GSTM1 (OR¼0.53, 95% CI: 0.201.37, p¼0.19) genotype was deleted in 54% cases compared to 39% in controls. Deletion of both GSTT1 and GSTM1 (OR¼ 2.96, 95% CI: 0.72-10.57, p¼0.04) genotype was found in 23% of cases than 13% in controls. Conclusions: Taken together, these results do not give evidence for association with either GSTM1 or GSTT1. However, greater degree of deletion of both GSTT1 and GSTM1 genotype may be a risk factor for AD. Study with a larger sample size is further required to address these uncertainties. P2-097
THE SYDNEY MEMORY AND AGEING STUDY (MAS): A POPULATION-BASED LONGITUDINAL INVESTIGATION OF COGNITIVE HEALTH IN THE ELDERLY
Nicole Kochan1, Henry Brodaty1,2, Julian Trollor1, Brian Draper1, Wei Wen1, Melissa Slavin1, Simone Reppermund1, John Crawford1, Kristan Kang1, G. A. (Tony) Broe3, Peter Schofield3, Perminder Sachdev1, 1 University of New South Wales, Sydney, Australia; 2Dementia Collaborative Research Centre, Sydney, Australia; 3Prince of Wales Medical Research Institute, Sydney, Australia. Contact e-mail: [email protected] Background: The Sydney Memory and Ageing Study (MAS) is a population-based longitudinal study of nondemented older individuals. The study aims to advance knowledge of causes, risk factors and protective factors, of neurocognitive disorders in the elderly by incorporating comprehensive and multidimensional investigations including neuroimaging and potential biomarkers. A second aim is to refine criteria for early diagnosis of prodromal stages of dementia. Methods: From 2005, 1037 community-dwelling persons, aged 70-90, were recruited randomly from the Australian Electoral Roll. At wave 1, participants received a comprehensive assessment: clinical examination, physical assessments (eg spirometry, balance), traditional and computerized neuropsychological assessments, donation of blood sample for biochemistry and DNA extraction/development of immortalized cell lines, proteomics, neuroimaging incorporating structural MRI, diffusion tensor imaging, susceptibility-weighted imaging and, for a subgroup, functional MRI protocol examining cortical responses to increasing cognitive challenge. Questionnaires regarding nutrition, current and previous levels of physical, cognitive and social activity and service utilization are collected and disease burden is calculated. Informants provide data on participants’ functional abilities and neuropsychiatric status. Participants receive a brief telephone assessment at 12 and 36-months and repeat comprehensive assessment every second year. Results: Wave 1 data collection was completed late 2007 and approximately half the
Poster Presentations P2 group have been seen for Wave 2. Cross-sectional data have raised interesting questions about the validity of current MCI diagnostic criteria. Over 95% of participants and/or their informants affirmed at least one of the questions about decline in memory and/or other cognitive abilities, calling into question the utility of the subjective complaints criterion. We have also highlighted the problems inherent in defining cognitive impairment for the MCI criteria and the considerable variability in prevalence depending on methods used to operationalize cognitive impairment. Early neuroimaging results, using the new DARTEL method of voxel-based morphometry (VBM) to evaluate the relationship between grey matter volume and verbal fluency performance, and the ability of DTI measures to reliably discriminate individuals with MCI from healthy elderly, are promising. Conclusions: The Memory and Ageing Study provides a large comprehensively assessed cohort with clinical, psychological, functional and biometric data, which will be a valuable resource for collaborative research on cognitive disorders in the elderly. P2-098
VERBAL FLUENCY AND PHYSICAL ACTIVITY IN THE AGING PROCESS: AN EPIDEMIOLOGICAL ˜ O PAULO, BRAZIL STUDY CARRIED OUT IN SA
Thais B. L. da Silva1, Moˆnica S. Yassuda2, 1University of Sa˜o Paulo, Sa˜o Paulo, Brazil; 2University of Sa˜o Paulo, Sa˜o Paulo, Brazil, Brazil. Contact e-mail: [email protected] Background: Studies have documented significant decline among the elderly in some cognitive abilities, including the executive functions associated with the ability to plan, monitor, organize, sort, among others. The verbal fluency test animal category has been considered an important measure of preservation of executive functions. To study the association between physical activity and cognition, by correlating performance on the verbal fluency test variables to the level of physical activity of participants, and socio-demographic variables among elderly residents in Ermelino Matarazzo, a poor district of Sa˜o Paulo city. Methods: 383 elderly (60 years and over) participated in a cross-sectional study which used epidemiological methodology. Physical activity was assessed by the IPAQ (International Physical Activity Questionnaire) and the VIGITEL questionnaire (Surveillance of Risk Factors for Chronic Diseases through Telephone Interviews). Cognition was assessed by the verbal fluency animal category test. Results: The performance in verbal fluency was compared among the elderly who were active and inactive in locomotion, walking and leisure. There was superior performance for the active elderly, however, the difference between the groups only approached and the statistical significance for locomotion and walking. There was significant difference between the active and inactive groups for the number of animals spoken in the first 15 seconds, suggesting that active seniors are faster in semantic search. Performance was higher among men, among younger elderly (60-69 years) and among older people with five or more years of schooling. Conclusions: Active lifestyle may influence cognitive performance. P2-099
EARLY WINDOW OF MORTALITY RISK ON 3XTGAD MICE TREATED WITH AN ANTIPSYCHOTIC DRUG AT ADVANCED STAGES OF THE DISEASE
Lydia Gimenez Llort1, Helga Rivas1, Xe`nia Planas-Pujol2, Josep GarreOlmo2, Frank M. Laferla3, Joan Vilalta-Franch4, Secundı´ Lopez-Pousa4, 1 Dept of Psychiatry & Forensic Medicine, Institute of Neurosciences, Autonomous University of Barcelona, Bellaterra, Barcelona, Spain; 2Research Unit. Hospital de Sta Caterina, Institut d’Assiste`ncia Sanita`ria, Salt, Girona, Spain; 3Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA; 4Memory and Dementia Assessment Unit (UVAMID), Hospital de Sta Caterina, Institut d’Assiste`ncia Sanita`ria, Salt, Girona, Spain. Contact e-mail: [email protected] Background: Psychosis, aggression, and agitation are common problems in patients with dementia, and when severe or persistent, can cause considerable patient distress and disability, as well as caregiver strain and early
P291
institutionalization. In April 2005, the FDA determined that atypical antipsychotics were associated with a significantly greater mortality risk compared to placebo which prompted the addition of an FDA black-box warning regarding this risk. Now, the ACNP White Paper (2008) has reviewed this relevant issue and made clinical and research recommendations regarding the use of antipsychotics in elderly dementia patients with psychosis and/or agitation. In a recent retrospective work, we have confirmed the increase of mortality risk in patients at advanced ages of the disease who received risperidone therapy but we could not find any relationship to metabolic syndrome nor history of heart disease. Now, we are studying and monitoring the putative effects of etiological factors in 3xTgAD mice (harbouring PS1M146V, APPSwe, tauP301L) receiving a low dose of risperidone at advanced stages of the disease. Methods: Cognitive, BPSDlike symptoms and IPGTT of 12 month-old (bA neuropathological stage) male adult 3xTgAD and NonTg mice were evaluated before the start of treatment. Thereafter, half of the 3xTgAD mice were daily treated with a low dose of risperidone. Behavior and survival curves were recorded thought the experiment till very advances stages of the disease (both bA and tau pathologies). Results: We have found a clear risk mortality window close to the start of the treatment. The treated animals did not get much benefits of risperidone neither at cognitive nor BPSD-like symptoms and long-term survival was also shorter as compared to saline-treated 3xTgAD and NTg mice Conclusions: We have replicated the increased mortality risk on 3xTgAD mice. Therefore this animal model can be very useful to study the physiopathogenic factors involved in this subject of considerable public health significance. This early window of increased risk mortality fits with that described also for cerebrovascular adverse events in elderly users of antipsychotics what helps to delimitate a critical time window for critical causal events. Work supported by SAF200613642,UVAMID.
P2-100
COGNITIVE LEISURE ACTIVITY AS A PROTECTIVE FACTOR IN A PROSPECTIVE AGEING STUDY IN GERMANY
Christine Sattler, Pablo Toro, Johannes Schro¨der, University of Heidelberg, Heidelberg, Germany. Contact e-mail: christine.sattler@med. uni-heidelberg.de Background: Growing epidemiological evidence suggests that premorbid participation in cognitive leisure activities reduces the risk of dementia. We investigated if this protective effect was present in the populationbased Interdisciplinary Longitudinal Study on Adult Development and Aging (ILSE) and thus modulated the risk for developing either mild cognitive impairment (MCI) or Alzheimer’s disease (AD) in a representative birth cohort born between 1930 and 1932. The investigation of a representative birth cohort offers decisive advantages, such as an exclusion of age effects and age-related cohort effects. Methods: 500 participants of the ILSE-study were examined in 1993/94 (t1), 1997/98 (t2) and 2005/07 (t3). Participants were carefully screened for physical and mental health trough extensive medical interviews as well as physical and neuropsychological examinations throughout all examination waves. In addition the participants were asked to fill out a questionnaire concerning their current frequency of participation in cognitive and other leisure activities (e. g. reading, solving crossword puzzles). Participants were categorized as highly, moderately or poorly cognitively active according to their questionnaire statements. Results: 381 participants of the original cohort were re-examined at t3. Prevalence of MCI increased from 13 % to 23 % and 29 % over time. In addition 7 % of the participants developed AD at t3. Subjects who were highly cognitively active at t1 showed a reduced risk of developing MCI or AD in the 13-year follow-up period compared to healthy controls (OR¼0.23, 95 % CI 0.06-0.81, p<0.05 - scores adjusted for education and household income). Conclusions: Our results confirm the hypothesis that a high level of premorbid cognitive activity constitutes a protective factor for the development of MCI and AD. This effect remains significant after adjustment for education and household income.