- Email: [email protected]
CSF AD-PROFILE IN DEMENTIA WITH LEWY BODIES: EFFECT ON CLINICAL PARAMETERS AND COGNITIVE DECLINE
Oral Sessions: O4-06: Dementia with Lewy Bodies
O4-05-06
RED BLOOD CELL FATTY ACID PROFILES ARE SIGNIFICANTLY ALTERED IN MILD COGNITIVE IMPAIRMENT AND ALZHEIMER’S DISEASE CASES AND POTENTIALLY DIAGNOSTICALLY RELEVANT
Michael Felix Fenech1, Philip Thomas2, Sau Lai Lee3, Jane Hecker4, Jeffrey Faunt5, 1CSIRO, Adelaide, Australia; 2CSIRO Food and Nutritional Sciences, Adelaide, Australia; 3University of Adelaide, Adelaide, Australia; 4 Calvary Rehabilitation Hospital, Walkerville, SA, Australia; 5Royal Adelaide Hospital, Adelaide, Australia. Contact e-mail: michael.fenech@ csiro.au Background: Dietary fatty acid (FA) intake is associated with risk for cognitive decline and dementia but the major differences in the red blood cell (RBC) FA profile that are associated with mild cognitive impairment (MCI) or Alzheimer’s disease (AD) remain undefined. The aim of this study was to determine the RBC FA profile that best distinguishes MCI and AD cases from healthy controls and the diagnostic value of these parameters. Methods: 20 newly clinically diagnosed MCI (age 58-89 years) and 20 AD patients (age 46-90 years) were recruited by experienced clinicians using NINCDS-ADRDA criteria together with 40 age and gender matched healthy controls (age 46-90 years). RBC FA profile was measured using gas liquid chromatography following one-step extraction and transmethylesterification. Results: The saturated FAs stearic acid, arachidic acid, behenic acid, tricosanoic acid and lignoceric acid were significantly elevated in the MCI cohort (all p < 0.005 or less) and palmitic acid (p<0.0001) was increased in both MCI and AD compared to controls. The monounsaturated fatty acid (MUFA) elaidic acid was also significantly elevated in both the MCI and AD cohorts (p¼0.003). The polyunsaturated fatty acid (PUFA) linolenic acid was significantly reduced in both MCI and AD relative to controls (p¼0.0003). Other PUFA were also significantly reduced in MCI cases including linolelaidic acid (p¼0.001), g-linolenic acid (p¼0.03), eicosatrienoic acid (p¼0.01), and arachidonic acid (p<0.0001). The long chain n-3 PUFA docosahexaenoic acid was also significantly reduced in both the MCI and AD cohorts compared to controls (p<0.0001). In MCI, the ROC curve area under the curve (AUC) was >0.80 for three saturated FAs (behenic acid, AUC¼0.80; stearic acid, AUC¼0.80 and palmitic acid, AUC¼0.85), the MUFA elaidic acid (AUC¼0.80) and the PUFA g-linolenic acid (AUC¼ 0.81). For the AD cohort the highest ROC curve AUC was found for palmitic acid (AUC¼0.75) and elaidic acid (AUC¼0.79). The best sensitivity (90, 85%) and specificity (70, 72%) was obtained for palmitic and stearic acid respectively in MCIs. Conclusions: RBC FA profiles could be used to potentially identify individuals who are at high risk for MCI/AD and inform the design of preventative dietary intervention. WEDNESDAY, JULY 16, 2014 ORAL SESSIONS O4-06 DEMENTIA WITH LEWY BODIES O4-06-01
A 5-YEAR LONGITUDINAL STUDY OF PATIENTS WITH DEMENTIA WITH LEWY BODIES AND ALZHEIMER’S DISEASE
Arvid Rongve1, Hogne Sønnesyn2, Ragnhild Skogseth3, Dag Aarsland2, 1 Helse Fonna, Haugesund, Norway; 2Stavanger University Hospital, Stavanger, Norway; 3Haraldsplass Hospital, Bergen, Norway. Contact e-mail: [email protected] Background: Lewy body dementia (LBD) is the second most common neurodegenerative dementia representing 15-20% of people with dementia. The clinical presentation is complex, and cognitive decline is usually accompanied by motor, neuropsychiatric, and autonomous symptoms and a variety of sleep disturbances. The clinical impact is therefore high, as shown in previous reports based on the DemVest cohort showing higher institutionalization (Rongve 2013), mortality (Østerhus 2013), and healthrelated costs (Vossius 2013) in LBD compared to AD. Few prospective studies of DLB exist. The aim of this study was to compare the rate of cognitive and functional decline in LBD and Alzheimer’s disease (AD) over 5
P261
years. Aim of the study: To study the clinical course over 5 years from diagnosis of mild dementia Methods: We consecutively included persons diagnosed with mild dementia according to consensus criteria for AD, LBD or other dementias from geriatric and old age psychiatric outpatient clinics in western Norway during 2005-2007 (the DemVest study). From April 2007 on only patients with LBD were included. Participants were enrolled in annual follow up examinations, which included clinical and neuropsychological examination using standardized tests. At baseline, blood tests and MRI were performed for all patients, and most people with suspect LBD underwent DaTSCAN. CSF was examined available in a subgroup. Clinical dementia diagnoses were made according to NINDS-ADRDA (probable and possible AD) and International consensus criteria for possible and probable DLB and PDD. Diagnoses were repeatedly revised by a consensus group. Global cognition was assessed using the MMSE, and function with the Clinical Dementia Rating scale sum of boxes (CDR). Results: Data are currently available for 211 patients, 127 with AD (71% female, age 75.5(7.7) years) and 55 with LBD (11 PDD) (44% female, 76.5(7.8) years). Cognition and function did not differ at baseline, mean MMSE score was 23.7(2.3) in AD and 23.9(3.0) in LBD. There were no significant difference at any time point in mean MMSE or CDR scores between AD and LBD patients (Figure). Conclusions: The rate of cognitive and functional decline did not differ between LBD and AD over 5 years. Our findings thus suggest that non-cognitive symptoms such as hallucinations, parkinsonism, sleep problems and autonomous dysfunction are driving the more severe prognosis in LBD. References: Rongve A, Vossius C, Nore S, Testad I, Aarsland D. Int J Geriatr Psychiatry. 2013 Aug 13. http://dx.doi.org/10.1002/gps. 4015. [Epub ahead of print] Vossius C, Rongve A, Testad I, Wimo A, Aarsland D. Am J Geriatr Psychiatry. 2013 Mar 13. pii: S1064-7481(12)00042-5. http://dx.doi.org/10.1016/j.jagp.2012.08.014. Østerhus R et al. Dem Ger Cogn Disord. In press.
O4-06-02
CSF AD-PROFILE IN DEMENTIA WITH LEWY BODIES: EFFECT ON CLINICAL PARAMETERS AND COGNITIVE DECLINE
Afina W. Lemstra1, Sietske A. Sikkes2, Charlotte E. Teunissen3, Annelies van der Vlies2, Philip Scheltens4, 1VU University Medical Center, Amsterdam, Netherlands; 2VU University Medical Center, Amsterdam, Netherlands; 3Alzheimer Center, VU Medical Center, Amsterdam, Netherlands; 4VU University Medical Center, Amsterdam, Netherlands. Contact e-mail: [email protected] Background: Dementia with Lewy Bodies (DLB) is considered the second most common neurodegenerative dementia disorder after Alzheimer’s disease (AD). DLB is an alpha-synucleinopathy, but a substantial proportion of DLB-patients has concomitant AD-pathology. Neuropathological studies suggest that AD-pathology influences disease progression in DLB. The effect of AD-pathology on clinical symptoms is less clear. In this study we investigated the influence of concomitant AD-pathology, as reflected by the presence of AD-biomarkers in the cerebrospinal fluid (CSF), on clinical characteristics, neuropsychological test performance and cognitive decline in a large DLB-cohort. Methods: 120 probable DLB-patients with CSF available were selected from the Amsterdam Dementia Cohort. Ab42, tau and ptau-181 were measured in CSF by ELISA. A CSF AD-profile was predefined by the formula Ab42/152+8.25xptau < 1 (Schoonenboom, 2012). Patients were divided in an AD-positive group
P262
Oral Sessions: O4-06: Dementia with Lewy Bodies
(DLB-AD+) and AD-negative group (DLB-AD-) based on this profile. Cross-sectional data on age, sex, extrapyramidal signs, MMSE, CAMcog, DAD, NPI and duration of disease were compared. Neuropsychological test scores were standardized and clustered into four cognitive domains (memory, executive functioning, attention and visuospatial abilities). Global cognitive decline was measured with the MMSE and linear mixed models were used to investigate the relationship with AD-profile. Results: A CSF AD-profile was found in 48 patients (40%). Patients in the DLBAD+ group were older (71 vs. 66 years, p ¼0.002), more often female (27.1 vs. 9.7%, p ¼0.023) and performed worse on daily functioning (Median DAD-scores 61.5/100 vs. 84/100, p ¼0.02). There were no differences in MMSE, CAMcog, NPI, or duration of disease. After correction for age, sex and education, patients in the DLB-AD+ group performed worse on memory tasks (OR¼0.53, 95%CI 0.29-0.96, p ¼0.035). Linear mixed models with a mean follow-up of 2 years (range 1-6 years) showed a trend towards faster decline on the MMSE in the DLB-AD+ group. Conclusions: This study in a large, clinically well-characterised cohort of probable DLB patients showed that concomitant AD-pathology is associated with worse performance in daily functioning and worse memory function. Longitudinal data suggest faster cognitive decline. In addition to data from neuropathological studies, these results confirm that AD-pathology has relevant additional clinical effects in DLB. O4-06-03
PREVALENCE OF DLB FEATURES IN POSSIBLE DEMENTIA WITH LEWY BODIES AND ITS RELATIONSHIP TO CHANGES IN DEMENTIA DIAGNOSTIC CATEGORY AFTER DOPAMINE TRANSPORTER IMAGING USING DATSCANÔ
Zuzana Walker1, Michael Rainer2, Alan Thomas3, Naji Tabet4, Fraser Inglis5, Mihaela Banica6, Igor D. Grachev7, Emilio Moreno8, Alessandro Padovani9, 1University College London, London, United Kingdom; 2Centre for Mental Health in Old Age, Vienna, Austria; 3Institute for Ageing and Health, Newcastle, United Kingdom; 4Brighton and Sussex Medical School, Brighton, United Kingdom; 5Glasgow Memory Clinic Ltd, Glasgow, United Kingdom; 6University of Trieste, Trieste, Italy; 7GE Healthcare, Princeton, New Jersey, United States; 8GE Healthcare, Madrid, Spain; 9Universit a degli Studi di Brescia AO Spedali Civili, Brescia, Italy. Contact e-mail: [email protected] Background: The clinical diagnosis of dementia with Lewy bodies (DLB) is based on core and suggestive features. We set out to investigate whether dopamine transporter imaging using DaTSCANÔ would help in diagnosing DLB (by changing the diagnosis from possible DLB to probable DLB or non-DLB) and to identify which core and suggestive features would most be associated with a follow-up diagnosis of probable DLB. Methods: 187 patients with possible DLB were recruited from 21 centres in 6 European countries. Patients were randomized to have a DaTSCANÔ (n¼127) or to have no imaging (Control group, n¼60). The proportion of patients with changes in clinical diagnosis was assessed in terms of DLB features at baseline and after obtaining DaTSCANÔ results. The evolution of features and diagnosis was compared at 8 and 24-weeks of follow-up. Results: 170 subjects were considered valid for the primary endpoint assessment. Overall prevalence of DLB features was similar between the two study groups. Parkinsonism was the most frequent DLB feature (29%), followed by fluctuations (28%), hallucinations (24%) and REM sleep behaviour disorders (17%). No patients reported neuroleptic sensitivity.More patients in the DaTSCANÔ group had a change in diagnostic category after 8 weeks (61% vs 4%; P<.0001) while at 24-weeks there continued to be a major difference between the two groups (71 vs 16% p<0.0001).Parkinsonism at baseline was more prevalent in probable DLB and was the only feature that evolved at 6-months follow-up particularly in patients with final diagnosis of probable DLB and abnormal DaTSCANÔ imaging results. UPDRS-III changes were in the same direction. There were no differences between the groups with regard to other clinical features at baseline and/or at 6 months. Conclusions: In subjects with possible DLB changes in diagnostic category were more frequent in the DaTSCANÔ group particularly in those with abnormal images. The clinical evolution over 6-months
without DaTSCANÔ did not impact the diagnosis. Parkinsonism, but not other clinical features increased during the 24-weeks of follow-up. O4-06-04
MULTIMODAL EEG-MRI IN THE DIFFERENTIAL DIAGNOSIS OF AD AND DLB
John-Paul Taylor1, Sean J. Colloby1, Kristinn Johnsen2, Gısli Holmar Johannesson2, 1Newcastle University, Newcastle upon Tyne, United Kingdom; 2Mentis Cura, Reykjavik, Iceland. Contact e-mail: [email protected] Background: The differential diagnosis of Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) remains challenging; currently the best neuroimaging discriminator is the single photon emission tomography (SPECT) based DaTscan. However this modality fails to diagnosis approximately 15-20% of DLB patients who, despite having cortical Lewy body disease, do not have a significant loss of dopaminergic neurones from their substantia nigra. Therefore other discriminatory biomarkers may be useful. The objective of the present study was to investigate whether combined electroencephalography (EEG) and magnetic resonance imaging (MRI) classifiers can assist in the differential diagnosis of DLB vs. AD. Methods: Fifty one subjects (30 AD, 21 DLB) underwent high density EEG and 3T T1 MR imaging. EEG classifiers (temporal and spatial) were generated using support vector machine (SVM) statistical pattern recognition algorithms. MRI indices were derived from standard automated anatomical labelling (AAL) regions that were found to differentially effect AD and DLB in a voxel-based morphometry (VBM) study using SPM8. Exploratory stepwise logistic regression analyses were then conducted to identify separate EEG and MRI predictors of AD and DLB. Lastly, a combined EEG-MRI predictive model was then generated in classifying AD and DLB. Results: The identified MRI indices were: right cerebellum lobule VIII, left hippocampus, left precentral gyrus and left inferior temporal gyrus. For EEG, logistic regression analysis revealed two classifiers (ADms and ADmsLP) predicted AD and DLB (model: c 2 ¼22.1, df¼2, p<0.001, Nagelkerke R 2 ¼0.47, classification accuracy ¼ 77% (AD 87%, DLB 62%)). For MRI, logistic regression analysis revealed that left hippocampus and left precentral regions predicted AD and DLB (model: c 2 ¼21.3, df¼2, p<0.001, Nagelkerke R 2 ¼ 0.46, classification accuracy ¼ 78% (AD 83%, DLB 71%)). However, a combined EEG-MRI model (4 parameters) showed improved classification (model: c 2 ¼36.6, df¼4, p<0.001, Nagelkerke R 2 ¼ 0.69, classification accuracy ¼86% (AD 90%, DLB 81%)). Conclusions: Although suggestive and requiring validation in independent cohorts,diagnostic performance (DLB sensitivity 91%, AD specificity 90%) could be improved when combining EEG and MRI parameters in the differential diagnosis of AD and DLB and thus may either represent alternative or adjunctive biomarkers to the DaTSCAN. O4-06-05
DATSCAN FINDINGS IN PATIENTS WITH REM SLEEP BEHAVIOR DISORDER AND/OR COGNITIVE IMPAIRMENT
Bradley F. Boeve1, Val J. Lowe2, Kejal Kantarci1, Jonathan Graff-Radford1, David Thomas Jones1, Patrick Peller1, Michelle M. Mielke1, Tanis J. Ferman3, Michael Silber1, Erik St. Louis1, Glenn Smith1, Jamie Bennett1, Jeremiah Aakre1, Vernon Pankratz1, David S. Knopman1, Ronald Carl Petersen2, 1Mayo Clinic, Rochester, Minnesota, United States; 2 Mayo Clinic Rochester, Rochester, Minnesota, United States; 3Mayo Clinic, Rochester, Minnesota, United States. Contact e-mail: vlowe@mayo. edu Background: We sought to analyze the findings on DaTscan among patients with idiopathic REM sleep behavior disorder (iRBD), amnestic mild cognitive impairment (aMCI), nonamnestic MCI (naMCI), Alzheimer’s dementia (ADem) and dementia with Lewy bodies (DLB). Reduced striatonigral uptake on DaTscan reflects dopamine deficiency, and this finding is typical of DLB. One would predict that those clinical syndromes associated with underlying Lewy body disease (LBD) pathology (eg, iRBD, naMCI and DLB) are more likely to have reduced striatonigral uptake compared to those with a non-LBD substrate (eg, aMCI and ADem). Methods: DaTscan imaging was performed 3-6 hours after
O4-05-06
RED BLOOD CELL FATTY ACID PROFILES ARE SIGNIFICANTLY ALTERED IN MILD COGNITIVE IMPAIRMENT AND ALZHEIMER’S DISEASE CASES AND POTENTIALLY DIAGNOSTICALLY RELEVANT
Michael Felix Fenech1, Philip Thomas2, Sau Lai Lee3, Jane Hecker4, Jeffrey Faunt5, 1CSIRO, Adelaide, Australia; 2CSIRO Food and Nutritional Sciences, Adelaide, Australia; 3University of Adelaide, Adelaide, Australia; 4 Calvary Rehabilitation Hospital, Walkerville, SA, Australia; 5Royal Adelaide Hospital, Adelaide, Australia. Contact e-mail: michael.fenech@ csiro.au Background: Dietary fatty acid (FA) intake is associated with risk for cognitive decline and dementia but the major differences in the red blood cell (RBC) FA profile that are associated with mild cognitive impairment (MCI) or Alzheimer’s disease (AD) remain undefined. The aim of this study was to determine the RBC FA profile that best distinguishes MCI and AD cases from healthy controls and the diagnostic value of these parameters. Methods: 20 newly clinically diagnosed MCI (age 58-89 years) and 20 AD patients (age 46-90 years) were recruited by experienced clinicians using NINCDS-ADRDA criteria together with 40 age and gender matched healthy controls (age 46-90 years). RBC FA profile was measured using gas liquid chromatography following one-step extraction and transmethylesterification. Results: The saturated FAs stearic acid, arachidic acid, behenic acid, tricosanoic acid and lignoceric acid were significantly elevated in the MCI cohort (all p < 0.005 or less) and palmitic acid (p<0.0001) was increased in both MCI and AD compared to controls. The monounsaturated fatty acid (MUFA) elaidic acid was also significantly elevated in both the MCI and AD cohorts (p¼0.003). The polyunsaturated fatty acid (PUFA) linolenic acid was significantly reduced in both MCI and AD relative to controls (p¼0.0003). Other PUFA were also significantly reduced in MCI cases including linolelaidic acid (p¼0.001), g-linolenic acid (p¼0.03), eicosatrienoic acid (p¼0.01), and arachidonic acid (p<0.0001). The long chain n-3 PUFA docosahexaenoic acid was also significantly reduced in both the MCI and AD cohorts compared to controls (p<0.0001). In MCI, the ROC curve area under the curve (AUC) was >0.80 for three saturated FAs (behenic acid, AUC¼0.80; stearic acid, AUC¼0.80 and palmitic acid, AUC¼0.85), the MUFA elaidic acid (AUC¼0.80) and the PUFA g-linolenic acid (AUC¼ 0.81). For the AD cohort the highest ROC curve AUC was found for palmitic acid (AUC¼0.75) and elaidic acid (AUC¼0.79). The best sensitivity (90, 85%) and specificity (70, 72%) was obtained for palmitic and stearic acid respectively in MCIs. Conclusions: RBC FA profiles could be used to potentially identify individuals who are at high risk for MCI/AD and inform the design of preventative dietary intervention. WEDNESDAY, JULY 16, 2014 ORAL SESSIONS O4-06 DEMENTIA WITH LEWY BODIES O4-06-01
A 5-YEAR LONGITUDINAL STUDY OF PATIENTS WITH DEMENTIA WITH LEWY BODIES AND ALZHEIMER’S DISEASE
Arvid Rongve1, Hogne Sønnesyn2, Ragnhild Skogseth3, Dag Aarsland2, 1 Helse Fonna, Haugesund, Norway; 2Stavanger University Hospital, Stavanger, Norway; 3Haraldsplass Hospital, Bergen, Norway. Contact e-mail: [email protected] Background: Lewy body dementia (LBD) is the second most common neurodegenerative dementia representing 15-20% of people with dementia. The clinical presentation is complex, and cognitive decline is usually accompanied by motor, neuropsychiatric, and autonomous symptoms and a variety of sleep disturbances. The clinical impact is therefore high, as shown in previous reports based on the DemVest cohort showing higher institutionalization (Rongve 2013), mortality (Østerhus 2013), and healthrelated costs (Vossius 2013) in LBD compared to AD. Few prospective studies of DLB exist. The aim of this study was to compare the rate of cognitive and functional decline in LBD and Alzheimer’s disease (AD) over 5
P261
years. Aim of the study: To study the clinical course over 5 years from diagnosis of mild dementia Methods: We consecutively included persons diagnosed with mild dementia according to consensus criteria for AD, LBD or other dementias from geriatric and old age psychiatric outpatient clinics in western Norway during 2005-2007 (the DemVest study). From April 2007 on only patients with LBD were included. Participants were enrolled in annual follow up examinations, which included clinical and neuropsychological examination using standardized tests. At baseline, blood tests and MRI were performed for all patients, and most people with suspect LBD underwent DaTSCAN. CSF was examined available in a subgroup. Clinical dementia diagnoses were made according to NINDS-ADRDA (probable and possible AD) and International consensus criteria for possible and probable DLB and PDD. Diagnoses were repeatedly revised by a consensus group. Global cognition was assessed using the MMSE, and function with the Clinical Dementia Rating scale sum of boxes (CDR). Results: Data are currently available for 211 patients, 127 with AD (71% female, age 75.5(7.7) years) and 55 with LBD (11 PDD) (44% female, 76.5(7.8) years). Cognition and function did not differ at baseline, mean MMSE score was 23.7(2.3) in AD and 23.9(3.0) in LBD. There were no significant difference at any time point in mean MMSE or CDR scores between AD and LBD patients (Figure). Conclusions: The rate of cognitive and functional decline did not differ between LBD and AD over 5 years. Our findings thus suggest that non-cognitive symptoms such as hallucinations, parkinsonism, sleep problems and autonomous dysfunction are driving the more severe prognosis in LBD. References: Rongve A, Vossius C, Nore S, Testad I, Aarsland D. Int J Geriatr Psychiatry. 2013 Aug 13. http://dx.doi.org/10.1002/gps. 4015. [Epub ahead of print] Vossius C, Rongve A, Testad I, Wimo A, Aarsland D. Am J Geriatr Psychiatry. 2013 Mar 13. pii: S1064-7481(12)00042-5. http://dx.doi.org/10.1016/j.jagp.2012.08.014. Østerhus R et al. Dem Ger Cogn Disord. In press.
O4-06-02
CSF AD-PROFILE IN DEMENTIA WITH LEWY BODIES: EFFECT ON CLINICAL PARAMETERS AND COGNITIVE DECLINE
Afina W. Lemstra1, Sietske A. Sikkes2, Charlotte E. Teunissen3, Annelies van der Vlies2, Philip Scheltens4, 1VU University Medical Center, Amsterdam, Netherlands; 2VU University Medical Center, Amsterdam, Netherlands; 3Alzheimer Center, VU Medical Center, Amsterdam, Netherlands; 4VU University Medical Center, Amsterdam, Netherlands. Contact e-mail: [email protected] Background: Dementia with Lewy Bodies (DLB) is considered the second most common neurodegenerative dementia disorder after Alzheimer’s disease (AD). DLB is an alpha-synucleinopathy, but a substantial proportion of DLB-patients has concomitant AD-pathology. Neuropathological studies suggest that AD-pathology influences disease progression in DLB. The effect of AD-pathology on clinical symptoms is less clear. In this study we investigated the influence of concomitant AD-pathology, as reflected by the presence of AD-biomarkers in the cerebrospinal fluid (CSF), on clinical characteristics, neuropsychological test performance and cognitive decline in a large DLB-cohort. Methods: 120 probable DLB-patients with CSF available were selected from the Amsterdam Dementia Cohort. Ab42, tau and ptau-181 were measured in CSF by ELISA. A CSF AD-profile was predefined by the formula Ab42/152+8.25xptau < 1 (Schoonenboom, 2012). Patients were divided in an AD-positive group
P262
Oral Sessions: O4-06: Dementia with Lewy Bodies
(DLB-AD+) and AD-negative group (DLB-AD-) based on this profile. Cross-sectional data on age, sex, extrapyramidal signs, MMSE, CAMcog, DAD, NPI and duration of disease were compared. Neuropsychological test scores were standardized and clustered into four cognitive domains (memory, executive functioning, attention and visuospatial abilities). Global cognitive decline was measured with the MMSE and linear mixed models were used to investigate the relationship with AD-profile. Results: A CSF AD-profile was found in 48 patients (40%). Patients in the DLBAD+ group were older (71 vs. 66 years, p ¼0.002), more often female (27.1 vs. 9.7%, p ¼0.023) and performed worse on daily functioning (Median DAD-scores 61.5/100 vs. 84/100, p ¼0.02). There were no differences in MMSE, CAMcog, NPI, or duration of disease. After correction for age, sex and education, patients in the DLB-AD+ group performed worse on memory tasks (OR¼0.53, 95%CI 0.29-0.96, p ¼0.035). Linear mixed models with a mean follow-up of 2 years (range 1-6 years) showed a trend towards faster decline on the MMSE in the DLB-AD+ group. Conclusions: This study in a large, clinically well-characterised cohort of probable DLB patients showed that concomitant AD-pathology is associated with worse performance in daily functioning and worse memory function. Longitudinal data suggest faster cognitive decline. In addition to data from neuropathological studies, these results confirm that AD-pathology has relevant additional clinical effects in DLB. O4-06-03
PREVALENCE OF DLB FEATURES IN POSSIBLE DEMENTIA WITH LEWY BODIES AND ITS RELATIONSHIP TO CHANGES IN DEMENTIA DIAGNOSTIC CATEGORY AFTER DOPAMINE TRANSPORTER IMAGING USING DATSCANÔ
Zuzana Walker1, Michael Rainer2, Alan Thomas3, Naji Tabet4, Fraser Inglis5, Mihaela Banica6, Igor D. Grachev7, Emilio Moreno8, Alessandro Padovani9, 1University College London, London, United Kingdom; 2Centre for Mental Health in Old Age, Vienna, Austria; 3Institute for Ageing and Health, Newcastle, United Kingdom; 4Brighton and Sussex Medical School, Brighton, United Kingdom; 5Glasgow Memory Clinic Ltd, Glasgow, United Kingdom; 6University of Trieste, Trieste, Italy; 7GE Healthcare, Princeton, New Jersey, United States; 8GE Healthcare, Madrid, Spain; 9Universit a degli Studi di Brescia AO Spedali Civili, Brescia, Italy. Contact e-mail: [email protected] Background: The clinical diagnosis of dementia with Lewy bodies (DLB) is based on core and suggestive features. We set out to investigate whether dopamine transporter imaging using DaTSCANÔ would help in diagnosing DLB (by changing the diagnosis from possible DLB to probable DLB or non-DLB) and to identify which core and suggestive features would most be associated with a follow-up diagnosis of probable DLB. Methods: 187 patients with possible DLB were recruited from 21 centres in 6 European countries. Patients were randomized to have a DaTSCANÔ (n¼127) or to have no imaging (Control group, n¼60). The proportion of patients with changes in clinical diagnosis was assessed in terms of DLB features at baseline and after obtaining DaTSCANÔ results. The evolution of features and diagnosis was compared at 8 and 24-weeks of follow-up. Results: 170 subjects were considered valid for the primary endpoint assessment. Overall prevalence of DLB features was similar between the two study groups. Parkinsonism was the most frequent DLB feature (29%), followed by fluctuations (28%), hallucinations (24%) and REM sleep behaviour disorders (17%). No patients reported neuroleptic sensitivity.More patients in the DaTSCANÔ group had a change in diagnostic category after 8 weeks (61% vs 4%; P<.0001) while at 24-weeks there continued to be a major difference between the two groups (71 vs 16% p<0.0001).Parkinsonism at baseline was more prevalent in probable DLB and was the only feature that evolved at 6-months follow-up particularly in patients with final diagnosis of probable DLB and abnormal DaTSCANÔ imaging results. UPDRS-III changes were in the same direction. There were no differences between the groups with regard to other clinical features at baseline and/or at 6 months. Conclusions: In subjects with possible DLB changes in diagnostic category were more frequent in the DaTSCANÔ group particularly in those with abnormal images. The clinical evolution over 6-months
without DaTSCANÔ did not impact the diagnosis. Parkinsonism, but not other clinical features increased during the 24-weeks of follow-up. O4-06-04
MULTIMODAL EEG-MRI IN THE DIFFERENTIAL DIAGNOSIS OF AD AND DLB
John-Paul Taylor1, Sean J. Colloby1, Kristinn Johnsen2, Gısli Holmar Johannesson2, 1Newcastle University, Newcastle upon Tyne, United Kingdom; 2Mentis Cura, Reykjavik, Iceland. Contact e-mail: [email protected] Background: The differential diagnosis of Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) remains challenging; currently the best neuroimaging discriminator is the single photon emission tomography (SPECT) based DaTscan. However this modality fails to diagnosis approximately 15-20% of DLB patients who, despite having cortical Lewy body disease, do not have a significant loss of dopaminergic neurones from their substantia nigra. Therefore other discriminatory biomarkers may be useful. The objective of the present study was to investigate whether combined electroencephalography (EEG) and magnetic resonance imaging (MRI) classifiers can assist in the differential diagnosis of DLB vs. AD. Methods: Fifty one subjects (30 AD, 21 DLB) underwent high density EEG and 3T T1 MR imaging. EEG classifiers (temporal and spatial) were generated using support vector machine (SVM) statistical pattern recognition algorithms. MRI indices were derived from standard automated anatomical labelling (AAL) regions that were found to differentially effect AD and DLB in a voxel-based morphometry (VBM) study using SPM8. Exploratory stepwise logistic regression analyses were then conducted to identify separate EEG and MRI predictors of AD and DLB. Lastly, a combined EEG-MRI predictive model was then generated in classifying AD and DLB. Results: The identified MRI indices were: right cerebellum lobule VIII, left hippocampus, left precentral gyrus and left inferior temporal gyrus. For EEG, logistic regression analysis revealed two classifiers (ADms and ADmsLP) predicted AD and DLB (model: c 2 ¼22.1, df¼2, p<0.001, Nagelkerke R 2 ¼0.47, classification accuracy ¼ 77% (AD 87%, DLB 62%)). For MRI, logistic regression analysis revealed that left hippocampus and left precentral regions predicted AD and DLB (model: c 2 ¼21.3, df¼2, p<0.001, Nagelkerke R 2 ¼ 0.46, classification accuracy ¼ 78% (AD 83%, DLB 71%)). However, a combined EEG-MRI model (4 parameters) showed improved classification (model: c 2 ¼36.6, df¼4, p<0.001, Nagelkerke R 2 ¼ 0.69, classification accuracy ¼86% (AD 90%, DLB 81%)). Conclusions: Although suggestive and requiring validation in independent cohorts,diagnostic performance (DLB sensitivity 91%, AD specificity 90%) could be improved when combining EEG and MRI parameters in the differential diagnosis of AD and DLB and thus may either represent alternative or adjunctive biomarkers to the DaTSCAN. O4-06-05
DATSCAN FINDINGS IN PATIENTS WITH REM SLEEP BEHAVIOR DISORDER AND/OR COGNITIVE IMPAIRMENT
Bradley F. Boeve1, Val J. Lowe2, Kejal Kantarci1, Jonathan Graff-Radford1, David Thomas Jones1, Patrick Peller1, Michelle M. Mielke1, Tanis J. Ferman3, Michael Silber1, Erik St. Louis1, Glenn Smith1, Jamie Bennett1, Jeremiah Aakre1, Vernon Pankratz1, David S. Knopman1, Ronald Carl Petersen2, 1Mayo Clinic, Rochester, Minnesota, United States; 2 Mayo Clinic Rochester, Rochester, Minnesota, United States; 3Mayo Clinic, Rochester, Minnesota, United States. Contact e-mail: vlowe@mayo. edu Background: We sought to analyze the findings on DaTscan among patients with idiopathic REM sleep behavior disorder (iRBD), amnestic mild cognitive impairment (aMCI), nonamnestic MCI (naMCI), Alzheimer’s dementia (ADem) and dementia with Lewy bodies (DLB). Reduced striatonigral uptake on DaTscan reflects dopamine deficiency, and this finding is typical of DLB. One would predict that those clinical syndromes associated with underlying Lewy body disease (LBD) pathology (eg, iRBD, naMCI and DLB) are more likely to have reduced striatonigral uptake compared to those with a non-LBD substrate (eg, aMCI and ADem). Methods: DaTscan imaging was performed 3-6 hours after