- Email: [email protected]
Acceleration of cortical thinning in women with Alzheimer's disease
Poster Presentations: P4 defined by i) restriction in bathing or dressing (level 1), ii) restriction in bathing or dressing and in transferring (level 2), iii) restriction in bathing or dressing and in transfer and in feeding (level 3). Guttman scale analysis was used to test hierarchical relationships and reproducibility and scalability were calculated. The evolution after the next follow-up, two to three years later was described. Results: 808 cases of incident dementia were included, 6 participants were excluded because of missing data on the Katz scale. The hierarchical model fitted 99.3% of the subjects at baseline: 546 subjects (68.2%) were not ADL-restricted (level 0), 123 (15.3%) were restricted in bathing or dressing (level 1), 99 (12.3%) were restricted in level 2, and 28 (3.5%) were in level 3 (restricted in the 4 items). The Guttman analysis resulted in a scalogram of four items of Katz (coefficient of reproducibility ¼ 99.5%, coefficient of scalability ¼ 97.1%). Only 6 subjects were discordant (0.7%). After two to three years of follow-up, there was a significant trend towards increasing disability but mortality rate was high, particularly in the most severely disabled subjects (80.8% from level 3). Conclusions: The four items of the Katz’s scale could be used as a hierarchical cumulative scale to summarize data and define disability profiles over time in elderly subjects with dementia. P4-118
NEUROANATOMICAL SPECIFICITY OF PSYCHOSIS, DELUSIONS AND HALLUCINATIONS IN ALZHEIMER’S DISEASE
Stephane Poulin1, Simon Ducharme2, Bradford Dickerson2, 1Universite Laval, Quebec city, Quebec, Canada; 2Massachusetts General Hospital, Charlestown, Massachusetts, United States. Contact e-mail: stephane. [email protected] Background: Psychotic symptoms have a major impact on Alzheimer’s disease (AD) and have been associated with faster cognitive decline, caregiver burden and institutionalization. Thus far neuroimaging studies (total number of studies¼19) of the neural basis of psychotic symptoms in AD have produced inconsistent results. This inconsistency may in part be explained by differences in the symptoms being studied-while some studies have investigated psychosis as a single entity, others have focused on delusions or hallucinations in isolation. In previous studies, 3 different types of contrast have been employed: 1) psychosis vs no psychosis - PnP 2) delusions vs no delusions - DnD 3) hallucinations vs no hallucinations - HnH. The objective of the present study was to test whether the independent variable definition might explain results heterogeneity. More specifically the objective was to verify whether these different contrasts (PnP, DnD, HnH) produce different cortical correlates of psychosis in a large sample of mild AD. Methods: Subjects were all mild AD from the Alzheimer’s Disease Neuroimaging Initiative. Delusions and hallucinations were assessed at study entry with the Neuropsychiatric Inventory - caregiver version. Psychosis was defined as the presence of delusions and/or hallucinations. The neuropsychiatric status of control subjects was verified at the 12-month follow-up visit to validate the absence of psychosis, delusions and hallucinations. Using advanced morphometric techniques, three sets of statistical surface maps were generated, one for each of the possible contrast (PnP, DnD, HnH) and compared. Results: The different contrasts were associated with different patterns of cortical atrophy. Delusions were associated with a large area of atrophy of the anterior portion of the left dorsolateral prefrontal cortex. Psychosis was associated with similar although smaller areas of atrophy. Hallucinations were associated with right ventromedial/anterior cingulate and left anterior cingulate atrophy, but with relative preservation of areas of bilateral parietal and occipital cortices. Conclusions: In this study, psychosis, delusions and hallucinations in subjects with mild AD were associated with different patterns of cortical atrophy. This study suggests that a more specific characterization of psychosis may be critical to identify its underlying neuronal circuits. P4-119
AN UNUSUAL CASE OF LOGOPENIC PROGRESSIVE APHASIA ASSOCIATED WITH CORTICOBASAL SYNDROME
Lize Jiskoot1, Frank Jan Jong2, John van Swieten3, 1Erasmus Medical Center, Rotterdam, Netherlands; 2Erasmus Medical Center, Rotterdam,
P747
Netherlands; 3Erasmus University Medical Center, Rotterdam, Netherlands. Contact e-mail: [email protected] Background: The overlap of corticobasal degeneration (CBD) with primary progressive aphasia (PPA) and frontotemporal dementia (FTD) is well-known and predicts underlying tau-positive pathology. Two PPA subtypes, progressive non-fluent aphasia and semantic dementia, are mostly associated with FTD pathology. A more recently defined third subtype, logopenic progressive aphasia (LPA) is typically associated with Alzheimer disease (AD) and underlying Alzheimer pathology. We present a patient with a combination of LPA and a corticobasal syndrome (CBS) in the absence of Alzheimer specific profile of CSF biomarkers. Results: E.H. is a 75-year old woman with a 2-year history of progressive word-finding difficulties initially without memory problems or personality changes. First evaluation showed difficulty starting and sparse, effortful halting speech, with frequent word distortions, phonemic errors, and impaired sentence repetition. Neurological examination was unremarkable. Neuropsychological evaluation: confirmed PPA classified as LPA according to Gorno-Tempini criteria, with mild deficits in memory, attention and visuospatial function. Clinical work-up: routine laboratory tests and CSF biomarkers for AD (Ab 1-42 1648 pg/ml and phospho-tau 181 56 pg/ml) were all normal. MRI showed left-sided frontal and parietal cortical atrophy (Figure 1a), 18FDG-PET hypometabolism in the left frontal and parietal and to a lesser extent left temporal and occipital lobes (Figure 1b). Follow-up: 3 years after symptom-onset the patient developed a right-sided pyramidal syndrome and dystonic movements of the right arm during gait (video), and a depression, in the presence of preserved disease insight. Personality changes and prominent memory deficits were still absent. The clinical presentation, CSF and imaging findings are strongly suggestive for CBD. Conclusions: This case is one of the few documented with both LPA and CBS. In contrast to previous clinicopathological studies, the present case of LPA with CBS has normal CSF biomarkers and is therefore unlikely to be associated with Alzheimer pathology. Amyloid-imaging might further help to exclude AD pathology, but was not performed. LPA is occasionally associated with CBS. Whether this reflects underlying FTD or Alzheimer pathology, or both remains to be elucidated.
P4-120
ACCELERATION OF CORTICAL THINNING IN WOMEN WITH ALZHEIMER’S DISEASE
Hanna Cho1, Sang Won Seo2, Seun Jeon3, Sue J. Kang4, Geon Ha Kim4, Young Noh4, Byoung Seok Ye4, Hee-Jin Kim5, Cindy Yoon6, Sung Tae Kim4, Jong-Min Lee3, Ju Hee Chin4, Duk L. Na2, 1Samsung Medical Center, Seoul, South Korea; 2Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 3 Hanyang University, Seoul, South Korea; 4Samsung Medical Center, Seoul, South Korea; 5Samsung Medical Center, Seoul, Seoul, South Korea; 6 Department of Neurology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea. Contact e-mail: iguhanna@ naver.com Background: Previous studies have consistently demonstrated that the incidence of Alzheimer’s disease (AD) is higher in women than in men. However, effects of gender differences over AD progression showed inconsistent results and also have received less attention than other demographics. Therefore, t he aim of this study is to investigate whether there exists gender difference on cortical thickness with respect to the disease progression of AD for five years. Methods: We prospectively recruited 36 patients with
P748
Poster Presentations: P4
early stage of Alzheimer’s disease (14 men and 22 women) and 14 normal controls. All subjects were assessed with neuropsychological tests and with magnetic resonance imaging at baseline and Year 1, Year 3 and Year 5. W e performed cortical thickness analysis using surface-based morphometry method of magnetic resonance imaging. Results: A t baseline, there were no differences in the cortical thickness between men and women with AD. However, over 5 years longitudinal follow-up, women with AD showed more rapid cortical thinning in the left prefrontal cortex, bilateral medial frontal cortex, bilateral tempo-parietal association cortex, and bilateral lateral temporal lobe, compared to men with AD. In contrast, there were no regions of significant rapid atrophy in men with AD. Conclusions: Our findings suggested that the women deteriorate faster in terms of cortical thickness than men in the AD progression, which might be related to cognitive reserve theory. P4-121
SIGNIFICANT RISK OF DEMENTIA IN SHUNTRESPONSIVE IDIOPATHIC NORMAL PRESSURE HYDROCEPHALUS
Ville Leinonen1, Irina Alafuzoff2, Sakari Savolainen1, Anna Sutela1, Jaana Rummukainen1, Mitja Kurki1, Hilkka Soininen3, Jaakko Rinne1, Juha E. J€a€askel€ainen1, Anne Koivisto1, 1Kuopio University Hospital, Kuopio, Finland; 2University of Eastern Finland, Kuopio, Finland; 3 University of Eastern Finland, Kuopio, Finland. Contact e-mail: ville. [email protected] Background: Idiopathic normal pressure hydrocephalus (iNPH) causes cognitive decline that can be alleviated by shunting, but long-term outcome studies are scarce. Our aim was to elucidate the long-term risk of cognitive decline in shunt-responsive iNPH patients. Methods: Initially 468 patients underwentclinical and radiological examination, 24hour intraventricular pressure monitoring, frontal cortical brain biopsy (Kuopio University Hospital NPH Registry www.uef.fi/nph). Accordingly 193 were diagnosed with iNPH and shunted, 157 (81%) were initially responding to the shunt and 146 were available to analyze the signs of subsequent dementia. The Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition, and specified memory disorder criteria were used. Results: At the end of follow-up (median 4.8 yrs), 117 (80%) of the 146 iNPH patients had cognitive decline and 67 (46%) had developed clinical dementia, most commonly iNPH-related dementia, Alzheimer’s disease (AD; n¼19; 13%) and vascular dementia. In multivariate analysis, memory deficit as the first symptom before the shunt (OR 18.3; 95% CI 1.9-175), male sex (3.29; 1.11-9.73), age (1.17 per year; 1.07-1.28), and follow-up time (1.20 per year; 1.02-1.40) predicted subsequent dementia. AD was predicted by amyloid-b alone (OR 4.6; 1.6-13) and together with hyperphosporylated tau (6.6; 1.0-43) in the brain biopsy. However, brain biopsy did not predict the initial shunt response. Noteworthy, 8 (5%) iNPH patients developed dementia - inspite of initial response to the shunt - without signs of any other neurodegenerative disease in clinical, neuroradiological, or frontal cortical brain biopsy evaluation. These 8 patients initially presented with a full triad of symptoms, gait disturbance being the most frequent initial symptom followed by deterioration in cognition. Conclusions: The novel findings in the 146 iNPH patients initially responsive to the CSF shunt were: (1) a significant risk of developing subsequent dementia during the follow-up, most commonly due to iNPH-related dementia followed by concurrent AD or vascular dementia; (2) a small subgroup developing dementia (iNPH dementia) without any other neurodegenerative comorbidities. These results warrant active neurological follow-up of shunted iNPH patients. P4-122
COGNITIVE EVIDENCE IN PEOPLE WITH ALZHEIMER’S DISEASE THAT COMPROMISED HIPPOCAMPAL NEUROGENESIS IS RELATED BOTH TO APOE-34 STATUS AND CSF BETAAMYLOID 42
Keith Wesnes1, 1Bracket Global, Goring on Thames, England, United Kingdom. Contact e-mail: [email protected]
Background: Emerging evidence suggests that decreased adult hippocampal neurogenesis represents an early critical event in the course of Alzheimer’s disease (AD). In mice, adult neurogenesis was reduced by knock-in alleles for human ApoE4. Decreased dentate gyrus (DG) neural progenitor cells proliferation has been observed in 3xTg-AD mice; this reduction being directly associated with the presence of Aß plaques and an increase in the number of Aß-containing neurons in the hippocampus. Cognitive tasks involving difficult object pattern separations (OPS) have been shown to reflect DG activity and thus neurogenesis in both animals and man. Data presented at this meeting (Wesnes K. Alzheimer’s & Dementia 2010, 6: Supplement e45) showed selective difficult OPS age-related declines in healthy individuals aged 18 to 87 (n¼3065); and selective declines in amnestic Mild Cognitive Impairment (n¼73). This study used the same OPS paradigm in ADto seek relationships with APOE4 status and CSF Aß42. Methods: The CDR System OPS task involves the presentation of pictures which must later be discriminated from closely similar pictures (difficult OPS); a paradigm shown by fMRI to reflect DG activity. This paper presents previously unanalysed and unpresented OPS data from 74 genotyped mild-moderate AD patients in whom CSF Aß42 was measured (Wesnes K et al, Acta Neurologica Scandinavica 2010, 122: 270-277). Results: APOE4 homozygotes were not compromised on the easy OPS compared with the other patients (E2/E3;E2/E4;E3/E3;E3/E4). In contrast the E4/E4 patients were poorer at the difficult OPS (F¼2.9, df 4,45 p¼0.031). In all patients CSF Aß42 correlated with the ability to make the difficult OPS discriminations (r¼0.3.p¼0.014), but not easier discriminations (r¼0.14). OPS decision speed correlated negatively, and thus the association was not due to increased impulsivity. No significant association was seen on a non-DG sensitive word recognition paradigm (r¼0.15). Conclusions: These are to our knowledge the first human OPS data to suggest a genetic link to poor hippocampal neurogenesis in AD; as well as a relationship to Aß42. Therapies which target neurogenesis may thus be useful in preventing the early stages of AD, notably in APOE4 carriers, and such a population would be suitable for long-term studies of such agents in preclinical AD.
P4-123
THE DYNAMIC CHANGING OF OCCIPITAL DEMENTIA AND POSTERIOR CORTICAL ATROPHY
Canyan Liu1, Jing Gao1, Na Niu1, 1Peking Union Medical College Hospital, Beijing, China. Contact e-mail: [email protected]
NEUROANATOMICAL SPECIFICITY OF PSYCHOSIS, DELUSIONS AND HALLUCINATIONS IN ALZHEIMER’S DISEASE
Stephane Poulin1, Simon Ducharme2, Bradford Dickerson2, 1Universite Laval, Quebec city, Quebec, Canada; 2Massachusetts General Hospital, Charlestown, Massachusetts, United States. Contact e-mail: stephane. [email protected] Background: Psychotic symptoms have a major impact on Alzheimer’s disease (AD) and have been associated with faster cognitive decline, caregiver burden and institutionalization. Thus far neuroimaging studies (total number of studies¼19) of the neural basis of psychotic symptoms in AD have produced inconsistent results. This inconsistency may in part be explained by differences in the symptoms being studied-while some studies have investigated psychosis as a single entity, others have focused on delusions or hallucinations in isolation. In previous studies, 3 different types of contrast have been employed: 1) psychosis vs no psychosis - PnP 2) delusions vs no delusions - DnD 3) hallucinations vs no hallucinations - HnH. The objective of the present study was to test whether the independent variable definition might explain results heterogeneity. More specifically the objective was to verify whether these different contrasts (PnP, DnD, HnH) produce different cortical correlates of psychosis in a large sample of mild AD. Methods: Subjects were all mild AD from the Alzheimer’s Disease Neuroimaging Initiative. Delusions and hallucinations were assessed at study entry with the Neuropsychiatric Inventory - caregiver version. Psychosis was defined as the presence of delusions and/or hallucinations. The neuropsychiatric status of control subjects was verified at the 12-month follow-up visit to validate the absence of psychosis, delusions and hallucinations. Using advanced morphometric techniques, three sets of statistical surface maps were generated, one for each of the possible contrast (PnP, DnD, HnH) and compared. Results: The different contrasts were associated with different patterns of cortical atrophy. Delusions were associated with a large area of atrophy of the anterior portion of the left dorsolateral prefrontal cortex. Psychosis was associated with similar although smaller areas of atrophy. Hallucinations were associated with right ventromedial/anterior cingulate and left anterior cingulate atrophy, but with relative preservation of areas of bilateral parietal and occipital cortices. Conclusions: In this study, psychosis, delusions and hallucinations in subjects with mild AD were associated with different patterns of cortical atrophy. This study suggests that a more specific characterization of psychosis may be critical to identify its underlying neuronal circuits. P4-119
AN UNUSUAL CASE OF LOGOPENIC PROGRESSIVE APHASIA ASSOCIATED WITH CORTICOBASAL SYNDROME
Lize Jiskoot1, Frank Jan Jong2, John van Swieten3, 1Erasmus Medical Center, Rotterdam, Netherlands; 2Erasmus Medical Center, Rotterdam,
P747
Netherlands; 3Erasmus University Medical Center, Rotterdam, Netherlands. Contact e-mail: [email protected] Background: The overlap of corticobasal degeneration (CBD) with primary progressive aphasia (PPA) and frontotemporal dementia (FTD) is well-known and predicts underlying tau-positive pathology. Two PPA subtypes, progressive non-fluent aphasia and semantic dementia, are mostly associated with FTD pathology. A more recently defined third subtype, logopenic progressive aphasia (LPA) is typically associated with Alzheimer disease (AD) and underlying Alzheimer pathology. We present a patient with a combination of LPA and a corticobasal syndrome (CBS) in the absence of Alzheimer specific profile of CSF biomarkers. Results: E.H. is a 75-year old woman with a 2-year history of progressive word-finding difficulties initially without memory problems or personality changes. First evaluation showed difficulty starting and sparse, effortful halting speech, with frequent word distortions, phonemic errors, and impaired sentence repetition. Neurological examination was unremarkable. Neuropsychological evaluation: confirmed PPA classified as LPA according to Gorno-Tempini criteria, with mild deficits in memory, attention and visuospatial function. Clinical work-up: routine laboratory tests and CSF biomarkers for AD (Ab 1-42 1648 pg/ml and phospho-tau 181 56 pg/ml) were all normal. MRI showed left-sided frontal and parietal cortical atrophy (Figure 1a), 18FDG-PET hypometabolism in the left frontal and parietal and to a lesser extent left temporal and occipital lobes (Figure 1b). Follow-up: 3 years after symptom-onset the patient developed a right-sided pyramidal syndrome and dystonic movements of the right arm during gait (video), and a depression, in the presence of preserved disease insight. Personality changes and prominent memory deficits were still absent. The clinical presentation, CSF and imaging findings are strongly suggestive for CBD. Conclusions: This case is one of the few documented with both LPA and CBS. In contrast to previous clinicopathological studies, the present case of LPA with CBS has normal CSF biomarkers and is therefore unlikely to be associated with Alzheimer pathology. Amyloid-imaging might further help to exclude AD pathology, but was not performed. LPA is occasionally associated with CBS. Whether this reflects underlying FTD or Alzheimer pathology, or both remains to be elucidated.
P4-120
ACCELERATION OF CORTICAL THINNING IN WOMEN WITH ALZHEIMER’S DISEASE
Hanna Cho1, Sang Won Seo2, Seun Jeon3, Sue J. Kang4, Geon Ha Kim4, Young Noh4, Byoung Seok Ye4, Hee-Jin Kim5, Cindy Yoon6, Sung Tae Kim4, Jong-Min Lee3, Ju Hee Chin4, Duk L. Na2, 1Samsung Medical Center, Seoul, South Korea; 2Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 3 Hanyang University, Seoul, South Korea; 4Samsung Medical Center, Seoul, South Korea; 5Samsung Medical Center, Seoul, Seoul, South Korea; 6 Department of Neurology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea. Contact e-mail: iguhanna@ naver.com Background: Previous studies have consistently demonstrated that the incidence of Alzheimer’s disease (AD) is higher in women than in men. However, effects of gender differences over AD progression showed inconsistent results and also have received less attention than other demographics. Therefore, t he aim of this study is to investigate whether there exists gender difference on cortical thickness with respect to the disease progression of AD for five years. Methods: We prospectively recruited 36 patients with
P748
Poster Presentations: P4
early stage of Alzheimer’s disease (14 men and 22 women) and 14 normal controls. All subjects were assessed with neuropsychological tests and with magnetic resonance imaging at baseline and Year 1, Year 3 and Year 5. W e performed cortical thickness analysis using surface-based morphometry method of magnetic resonance imaging. Results: A t baseline, there were no differences in the cortical thickness between men and women with AD. However, over 5 years longitudinal follow-up, women with AD showed more rapid cortical thinning in the left prefrontal cortex, bilateral medial frontal cortex, bilateral tempo-parietal association cortex, and bilateral lateral temporal lobe, compared to men with AD. In contrast, there were no regions of significant rapid atrophy in men with AD. Conclusions: Our findings suggested that the women deteriorate faster in terms of cortical thickness than men in the AD progression, which might be related to cognitive reserve theory. P4-121
SIGNIFICANT RISK OF DEMENTIA IN SHUNTRESPONSIVE IDIOPATHIC NORMAL PRESSURE HYDROCEPHALUS
Ville Leinonen1, Irina Alafuzoff2, Sakari Savolainen1, Anna Sutela1, Jaana Rummukainen1, Mitja Kurki1, Hilkka Soininen3, Jaakko Rinne1, Juha E. J€a€askel€ainen1, Anne Koivisto1, 1Kuopio University Hospital, Kuopio, Finland; 2University of Eastern Finland, Kuopio, Finland; 3 University of Eastern Finland, Kuopio, Finland. Contact e-mail: ville. [email protected] Background: Idiopathic normal pressure hydrocephalus (iNPH) causes cognitive decline that can be alleviated by shunting, but long-term outcome studies are scarce. Our aim was to elucidate the long-term risk of cognitive decline in shunt-responsive iNPH patients. Methods: Initially 468 patients underwentclinical and radiological examination, 24hour intraventricular pressure monitoring, frontal cortical brain biopsy (Kuopio University Hospital NPH Registry www.uef.fi/nph). Accordingly 193 were diagnosed with iNPH and shunted, 157 (81%) were initially responding to the shunt and 146 were available to analyze the signs of subsequent dementia. The Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition, and specified memory disorder criteria were used. Results: At the end of follow-up (median 4.8 yrs), 117 (80%) of the 146 iNPH patients had cognitive decline and 67 (46%) had developed clinical dementia, most commonly iNPH-related dementia, Alzheimer’s disease (AD; n¼19; 13%) and vascular dementia. In multivariate analysis, memory deficit as the first symptom before the shunt (OR 18.3; 95% CI 1.9-175), male sex (3.29; 1.11-9.73), age (1.17 per year; 1.07-1.28), and follow-up time (1.20 per year; 1.02-1.40) predicted subsequent dementia. AD was predicted by amyloid-b alone (OR 4.6; 1.6-13) and together with hyperphosporylated tau (6.6; 1.0-43) in the brain biopsy. However, brain biopsy did not predict the initial shunt response. Noteworthy, 8 (5%) iNPH patients developed dementia - inspite of initial response to the shunt - without signs of any other neurodegenerative disease in clinical, neuroradiological, or frontal cortical brain biopsy evaluation. These 8 patients initially presented with a full triad of symptoms, gait disturbance being the most frequent initial symptom followed by deterioration in cognition. Conclusions: The novel findings in the 146 iNPH patients initially responsive to the CSF shunt were: (1) a significant risk of developing subsequent dementia during the follow-up, most commonly due to iNPH-related dementia followed by concurrent AD or vascular dementia; (2) a small subgroup developing dementia (iNPH dementia) without any other neurodegenerative comorbidities. These results warrant active neurological follow-up of shunted iNPH patients. P4-122
COGNITIVE EVIDENCE IN PEOPLE WITH ALZHEIMER’S DISEASE THAT COMPROMISED HIPPOCAMPAL NEUROGENESIS IS RELATED BOTH TO APOE-34 STATUS AND CSF BETAAMYLOID 42
Keith Wesnes1, 1Bracket Global, Goring on Thames, England, United Kingdom. Contact e-mail: [email protected]
Background: Emerging evidence suggests that decreased adult hippocampal neurogenesis represents an early critical event in the course of Alzheimer’s disease (AD). In mice, adult neurogenesis was reduced by knock-in alleles for human ApoE4. Decreased dentate gyrus (DG) neural progenitor cells proliferation has been observed in 3xTg-AD mice; this reduction being directly associated with the presence of Aß plaques and an increase in the number of Aß-containing neurons in the hippocampus. Cognitive tasks involving difficult object pattern separations (OPS) have been shown to reflect DG activity and thus neurogenesis in both animals and man. Data presented at this meeting (Wesnes K. Alzheimer’s & Dementia 2010, 6: Supplement e45) showed selective difficult OPS age-related declines in healthy individuals aged 18 to 87 (n¼3065); and selective declines in amnestic Mild Cognitive Impairment (n¼73). This study used the same OPS paradigm in ADto seek relationships with APOE4 status and CSF Aß42. Methods: The CDR System OPS task involves the presentation of pictures which must later be discriminated from closely similar pictures (difficult OPS); a paradigm shown by fMRI to reflect DG activity. This paper presents previously unanalysed and unpresented OPS data from 74 genotyped mild-moderate AD patients in whom CSF Aß42 was measured (Wesnes K et al, Acta Neurologica Scandinavica 2010, 122: 270-277). Results: APOE4 homozygotes were not compromised on the easy OPS compared with the other patients (E2/E3;E2/E4;E3/E3;E3/E4). In contrast the E4/E4 patients were poorer at the difficult OPS (F¼2.9, df 4,45 p¼0.031). In all patients CSF Aß42 correlated with the ability to make the difficult OPS discriminations (r¼0.3.p¼0.014), but not easier discriminations (r¼0.14). OPS decision speed correlated negatively, and thus the association was not due to increased impulsivity. No significant association was seen on a non-DG sensitive word recognition paradigm (r¼0.15). Conclusions: These are to our knowledge the first human OPS data to suggest a genetic link to poor hippocampal neurogenesis in AD; as well as a relationship to Aß42. Therapies which target neurogenesis may thus be useful in preventing the early stages of AD, notably in APOE4 carriers, and such a population would be suitable for long-term studies of such agents in preclinical AD.
P4-123
THE DYNAMIC CHANGING OF OCCIPITAL DEMENTIA AND POSTERIOR CORTICAL ATROPHY
Canyan Liu1, Jing Gao1, Na Niu1, 1Peking Union Medical College Hospital, Beijing, China. Contact e-mail: [email protected]