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Controversies of neurobiological correlates of apathy in Alzheimer's disease: A systematic review
P514
Poster Presentations: P3
Table 1 Baseline characteristics according to the two amnestic MCI subtypes
Demographics Age (years) Female Symptom duration (years) Education (years) K-MMSE Global deterioration scale CDR CDR-SB Geriatric depression scale Vascular risk factors Hypertension Diabetes mellitus Hyperlipidemia Cardiac disease Stroke history
Total (n¼62)
Retentiondeficit group (n¼41)
Retrievaldeficit group (n¼21)
67.3 6 8.1 33 (53.2) 3.2 6 3.5
66.8 6 8.2 20 (48.8) 3.4 6 4.0
68.2 6 7.9 13 (61.9) 2.9 6 2.2
0.528 0.327 0.611
11.8 6 5.3 27.7 6 1.7 3.0 6 0.0
12.6 6 5.3 27.9 6 1.7 3.0 6 0.0
10.4 6 5.3 27.4 6 1.7 3.0 6 0.0
0.117 0.270 >0.999
0.5 6 0.0 0.8 6 0.4 11.9 6 6.2
0.5 6 0.0 0.8 6 0.3 11.4 6 6.2
0.5 6 0.0 0.8 6 0.5 12.7 6 6.4
>0.999 0.668 0.443
26 (41.9) 9 (14.5) 14 (22.6) 9 (14.5) 6 (9.7)
12 (29.3) 4 (9.8) 10 (24.4) 6 (14.6) 4 (9.8)
14 (66.7) 5 (23.8) 4 (19.0) 3 (14.3) 2 (9.5)
0.005* 0.251 0.755 >0.999 >0.999
P value
Table 3 MRI findings of the two amnestic MCI subtypes
MTA (score 2) WMH ( moderate) Lacunar infarcts (number 3) Microbleeds (number 3)
Table 2 Neuropsychological profiles of the two amnestic MCI subtypes Retention-deficit group (n¼41) Digit span forward backward K-BNT RCFT copy score Verbal memory (SVLT) immediate recall total delayed recall recognition Visual memory (RCFT) immediate recall delayed recall recognition COWAT animal market phonemic total K-CWST color reading
Retrieval-deficit group (n¼21)
P value
6.6 6 1.2 4.4 6 1.4 47.1 6 7.0 34.5 6 2.0
6.6 6 1.1 4.1 6 1.1 45.6 6 7.0 34.1 6 1.8
0.965 0.291 0.427 0.513
14.34 6 2.8 3.0 6 2.0 8.8 6 2.0
16.9 6 3.9 2.5 6 1.3 10.1 6 1.0
0.012* 0.200 0.001*
13.3 6 6.4 13.5 6 6.3 9.5 6 2.2
12.9 6 6.8 12.4 6 5.8 9.4 6 1.4
0.831 0.487 0.948
14.4 6 3.2 15.0 6 5.6 24.4 6 6.9 91.3 6 13.4
14.2 6 3.4 16.8 6 4.9 24.4 6 9.0 86.2 6 21.0
0.865 0.213 0.985 0.315
MCI, mild cognitive impairment; K-BNT, Korean-Boston Naming Test; RCFT, Rey Complex Figure test; COWAT, Controlled Oral Word Association Test; K-CWST, Korean-Color Word Stroop Test. Values are presented as mean 6 standard deviation. The statistical analysis between two groups was done by the t-test or Mann-Whitney test. *P<0.05.
Retrievaldeficit group
P value
23.3% 25.6% 5.6% 16.0%
26.7% 15.8% 0.0% 0.0%
>0.999 0.513 >0.999 0.290
MRI, magnetic resonance imaging; MCI, mild cognitive impairment; MTA, medial temporal atrophy; WMH, white matter hyperintensities. The statistical analysis between two groups was done by the Fisher’s exact test. P3-175
MCI, mild cognitive impairment; K-MMSE, Korean version of MiniMental State Examination; CDR, Clinical Dementia Rating; CDR-SB, CDR-sum of boxes. Values are presented as mean 6 standard deviation or as number (percentage) of patients. The statistical analysis between two groups was done by the t-test and chisquare or Fisher’s exact test. *P<0.05.
Retentiondeficit group
RELATIONSHIPS BETWEEN GLOBAL COGNITIVE DYSFUNCTION AND PET BIOMARKERS IN NORMAL AGING, MILD COGNITIVE IMPAIRMENT AND ALZHEIMER’S DISEASE
Eun Hyun Seo1, Dong Young Lee2, IL Han Choo2, Bo Kyung Sohn3, Jee Wook Kim4, Yu Kyeong Kim5, Eun Jin Yoon2, Jong Inn Woo2, 1Seoul National University, Seoul, South Korea; 2Seoul National University Hospital, Seoul, South Korea; 3Seoul National University, Seoul, South Korea; 4Department of Neuropsychiatry, Hallym University Hangang Sacred Heart Hospital, Seoul, South Korea; 5Seoul National University Bundang Hospital, Seongnam, South Korea. Background: Background: The relationship between Alzheimer’s disease (AD) pathological burdens and cognitive dysfunction still remain unclear. This study aimed to investigate the relationships of global cognitive dysfunction with cerebral beta-amyloid beta (burden and synaptic dysfunction, measured by [11 C]-labeled Pittsburgh Compound B (PiB)-positron emission tomography (PET) and [18 F] fluorodeoxyglucose (FDG)-PET, respectively, in cognitively normal (CN), mild cognitive impairment (MCI) and AD dementia. Methods: Twenty nine cognitively normal (CN) elderly, 30 subjects with mild cognitive impairment (MCI), and 26 with AD underwent clinical evaluation, PiB-PET and FDG-PET scanning. Two total scores (TS-l and TS-ll) of the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery (CERAD-NP) were calculated. Data were analyzed on a voxel-basis using statistical parametric mapping 2. Each TS was used as a covariate to find regions showing significant voxel-wise correlations (linear regression models adjusted for demographic influences). Results: For whole group, both TS showed negative correlations with Ab deposition in frontal and temporopaietal regions. Similarly, both TSs showed positive correlations with regional cerebral glucose metabolism (rCMglc) in frontal and temporopaietal regions. In CN, both TSs showed negative correlations with Ab deposition in left fusiform, left lingual gyrus, left inferior frontal gyrus and bilateral subcortical regions. TS-l showed positive correlations with rCMglc in left precuneus and right cuneus and TS-ll showed correlations in the slightly wider areas including bilateral parietal and frontal gyri and left temporal gyus. In regard of MCI, both TSs showed positive correlations with rCMglc in the bilateral frontal gyri and bilateral thalamus, whereas no correlation between each TS and Ab deposition was found. For AD, TS-l showed positive correlations with rCMglc in right inferior temporal gyrus and TS-ll showed correlations in bilateral inferior temporal gyri, whereas any correlation between each TS and Ab deposition was not found. Conclusions: Our results suggest that although both cerebral Ab burden and synaptic dysfunction have close relationships with general cognition, each of them probably makes differential contributions to cognitive decline according to the cognitive subgroups. P3-176
CONTROVERSIES OF NEUROBIOLOGICAL CORRELATES OF APATHY IN ALZHEIMER’S DISEASE: A SYSTEMATIC REVIEW
Florindo Stella1, Marcia Radanovic2, Ivan Aprahamian3, Sergio Hototian4, Michelle Ljubetic5, Larissa Andrade6, Orestes Forlenza7, 1UNESP -
Poster Presentations: P3 University Estadual Paulista, Biosciences Institute, Rio Claro, Sao Paulo, Brazil; 2Laboratory of Neurosciences - FMUSP, S~ao Paulo, Brazil; 3 Institute of Psychiatry - Hospital das Clınicas da FMUSP, S~ao Paulo, Brazil; 4Laboratory of Neurosciences, Sao Paulo, Brazil; 5Laboratory of Neurosciences, University of Sao Paulo, Brazil; 6UNESP - University Estadual Paulista, Rio Claro, Sao Paulo, Brazil; 7Laboratory of Neurosciences - FMUSP, S~ ao Paulo, Brazil. Background: Apathy has been reported as the most common neuropsychiatric syndrome in patients with Alzheimer’s disease (AD) with prevalence of 55-70%. Despite high prevalence, neurobiological correlates seem to be controversial. Dysfunction in frontal, temporal or parietal cortex, and basal ganglia have been mentioned in several studies involving structural and functional neuroimaging on apathy in AD. The aim of this study was to analyze neurobiological correlates of apathy in AD based on evidences of the literature involving structural or functional neuroimaging and classical AD biomarkers. Methods: We made a systematic review of publications, which included association between apathy in AD and structural (MRI, CT, DTI) or functional (PET, SPECT, spectroscopy) neuroimaging, and classical AD biomarkers (allele epsilon 4, APOE, beta-amyloid, neurofibrillary tangles). Results: We found 66 articles (27 were inserted in our analysis; 39 were excluded). The 27 publications were divided into two parts: brain neuroimaging (23 studies); and brain neurobiological biomarkers (5 studies). One study was involved in both parts. Frontal region was the most focused structure (17 studies) involving ortibofrontal, middle, and dorsolateral areas. Anterior cingulate (12 studies) was the second emphasized region, followed by temporal (7 studies), basal ganglia (7 studies), and parietal region (4 studies). Three investigations found no correlation between apathy and brain regions. More than one region was analyzed in the same study. Cognitive processes were correlated with specific brain regions. For instance, dysfunction of frontal areas have been linked to decline in planning and decision making, which are crucial for organizing and behavior performance. Disturbances of anterior cingulate were related to loss of motivation, loss of goaldirected behavior, and emotional blunting. Hypoactivity of basal ganglia was connected with decrease of dopaminergic process and loss of motor performance in motivated behavior. Atrophy of Meynert nucleus was linked to cholinergic and cognition decline, related to cognitive support for motivated behavior. Conclusions: Despite frontal regions (associated with planning and decision making) and anterior cingulate (related to emotional blunting and loss of motivation) have been considered crucial structures associated with apathy in AD, the results from studies remain controversial.
P3-177
COMBINING CLASSICAL CONDITIONING AND BRAIN-STATE CLASSIFICATION FOR THE DEVELOPMENT OF A BRAIN-COMPUTER INTERFACE (BCI) FOR ALZHEIMER’S PATIENTS
Giulia Liberati1, Ralf Veit2, Josue Dalboni da Rocha3, Sunjung Kim2, Dorothee Lule4, Christine von Arnim4, Antonino Raffone5, Marta Olivetti Belardinelli5, Niels Birbaumer2, Ranganatha Sitaram2, 1 Interuniversity Centre for Research on Cognitive Processing in Natural and Artificial Systems, Rome, Italy; 2Institute of Medical Psychology and Behavioral Neurobiology, Eberhard Karls-University, T€ubingen, Germany; 3 Institute of Medical Psychology and Behavioral Neurobiology, Eberhard Karls-University, T€ ubingen, Germany; 4Neurophysiology - Department of Neurology, University of Ulm, Ulm, Germany; 5Interuniversity Centre for Research on Cognitive Processing in Natural and Artificial Systems, Rome, Italy. Background: Alzheimer’s Disease (AD) patients who have lost the ability to communicate verbally may benefit from a Brain-Computer Interface (BCI), which could allow them to convey basic thoughts and emotions, e.g. by associating affirmative and non-affirmative thinking to a positive and a negative emotion, respectively. One possibility to develop a BCI that can be used with AD patients is to modulate brain responses with a se-
P515
mantic classical conditioning paradigm, in order to associate congruent and incongruent word pairs with emotionally positive and negative stimuli, facilitating the discrimination between “affirmative” and “non-affirmative” thinking. Using a classical conditioning paradigm is convenient, since it does not require AD patients to put active effort in learning how the BCI works. Methods: In our classical conditioning paradigm, already tested on 11 healthy subjects, the unconditioned stimuli consist of a positive and negative emotional sound (a baby laugh and a scream, respectively). The conditioned stimuli, presented aurally, are congruent (e.g. ’fruit-apple’) and incongruent (e.g. ’fruit-dog’) word pairs. During the conditioning acquisition, congruent and incongruent word pairs are associated to the baby laugh and the scream respectively. Functional magnetic resonance imaging (fMRI) will be performed on AD patients (Mini Mental State Examination score: 18-24; intact auditory system) on a 3T scanner. To classify the signals corresponding to congruent and incongruent word pairs, both univariate (General Linear Model) and multivariate (Support Vector Machine, SVM) analyses will be performed. Results: Both univariate and multivatiate analyses on healthy subjects confirmed the possibility to discriminate between affirmative and non-affirmative responses. We hypothesize that a similar differentiation may be found in AD patients, since classical conditioning was demonstrated to be possible, at least to some extent, in these patients.The study with AD patients is ongoing, and preliminary results will be presented during the conference. Conclusions: The encouraging results obtained with healthy subjects show that basic affirmative/non affirmative thinking discrimination is possible within an fMRI-BCI setting. The development of a BCI for AD patients could be an important step for allowing not only basic communication, but possibly lending a path for rehabilitation and diagnosis.
P3-178
ASSOCIATION BETWEEN DEPRESSIVE SYMPTOMS, COGNITIVE DECLINE, AND WHITE MATTER INTEGRITY IN COGNITIVELY NORMAL ADULTS WITH A FAMILY HISTORY OF ALZHEIMER’S DISEASE
Grace Lee1, Katie Smith2, Lori Holleran2, Ahra Ko3, George Bartzokis3, Po-Haong Lu3, 1UCLA Easton Center for Alzheimer’s Disease Research, Los Angeles, California, United States; 2Pepperdine, Los Angeles, California, United States; 3UCLA, Los Angeles, California, United States. Background: Depression is frequently observed in patients with Alzheimer’s Disease (AD) and has been shown to predict higher rates of progression from mild cognitive impairment (MCI) to AD. The neurobiological mechanism underlying this relationship may be related to white matter breakdown, which has been independently associated with both depression and AD. The current study examined the relationship between depressive symptoms, decline in processing speed, and white matter integrity on diffusion tensor imaging (DTI) in a high-risk sample of cognitively normal adults with a family history of AD. Methods: 51 subjects (29 males) from the UCLA Alzheimer’s Disease Research Center with a family history of AD who were cognitively normal at baseline with at least 2 follow-up visits were included in the present study. Subjects ranged in age from 47 to 88 years (mean¼66.1, sd¼8.5). Correlation analyses between baseline scores on the Geriatric Depression Scale (GDS), change in cognitive processing speed (CPS: WAIS-III Digit Symbol, Trails A) from baseline to 2-year follow-up, and DTI measures of white matter integrity were computed. Binary logistic regression was used to determine the association between GDS and conversion to amnestic MCI. Results: Baseline GDS scores were negatively correlated with change in CPS over 2 years (r ¼ -0.314, p¼.025). In a subset of subjects (n¼21) who underwent magnetic resonance imaging, GDS was also significantly correlated with fractional anisotropy (r ¼ -0.484, p¼.026) and marginally correlated with radial diffusivity (r ¼ 0.388, p¼.082) in frontal white matter. Both relationships indicate higher scores on the GDS were associated with reduced white matter integrity. In the entire sample, GDS was a significant predictor of conversion to MCI (p¼.015), even after controlling for age, years of education, and gender. Conclusions: Depressive
Poster Presentations: P3
Table 1 Baseline characteristics according to the two amnestic MCI subtypes
Demographics Age (years) Female Symptom duration (years) Education (years) K-MMSE Global deterioration scale CDR CDR-SB Geriatric depression scale Vascular risk factors Hypertension Diabetes mellitus Hyperlipidemia Cardiac disease Stroke history
Total (n¼62)
Retentiondeficit group (n¼41)
Retrievaldeficit group (n¼21)
67.3 6 8.1 33 (53.2) 3.2 6 3.5
66.8 6 8.2 20 (48.8) 3.4 6 4.0
68.2 6 7.9 13 (61.9) 2.9 6 2.2
0.528 0.327 0.611
11.8 6 5.3 27.7 6 1.7 3.0 6 0.0
12.6 6 5.3 27.9 6 1.7 3.0 6 0.0
10.4 6 5.3 27.4 6 1.7 3.0 6 0.0
0.117 0.270 >0.999
0.5 6 0.0 0.8 6 0.4 11.9 6 6.2
0.5 6 0.0 0.8 6 0.3 11.4 6 6.2
0.5 6 0.0 0.8 6 0.5 12.7 6 6.4
>0.999 0.668 0.443
26 (41.9) 9 (14.5) 14 (22.6) 9 (14.5) 6 (9.7)
12 (29.3) 4 (9.8) 10 (24.4) 6 (14.6) 4 (9.8)
14 (66.7) 5 (23.8) 4 (19.0) 3 (14.3) 2 (9.5)
0.005* 0.251 0.755 >0.999 >0.999
P value
Table 3 MRI findings of the two amnestic MCI subtypes
MTA (score 2) WMH ( moderate) Lacunar infarcts (number 3) Microbleeds (number 3)
Table 2 Neuropsychological profiles of the two amnestic MCI subtypes Retention-deficit group (n¼41) Digit span forward backward K-BNT RCFT copy score Verbal memory (SVLT) immediate recall total delayed recall recognition Visual memory (RCFT) immediate recall delayed recall recognition COWAT animal market phonemic total K-CWST color reading
Retrieval-deficit group (n¼21)
P value
6.6 6 1.2 4.4 6 1.4 47.1 6 7.0 34.5 6 2.0
6.6 6 1.1 4.1 6 1.1 45.6 6 7.0 34.1 6 1.8
0.965 0.291 0.427 0.513
14.34 6 2.8 3.0 6 2.0 8.8 6 2.0
16.9 6 3.9 2.5 6 1.3 10.1 6 1.0
0.012* 0.200 0.001*
13.3 6 6.4 13.5 6 6.3 9.5 6 2.2
12.9 6 6.8 12.4 6 5.8 9.4 6 1.4
0.831 0.487 0.948
14.4 6 3.2 15.0 6 5.6 24.4 6 6.9 91.3 6 13.4
14.2 6 3.4 16.8 6 4.9 24.4 6 9.0 86.2 6 21.0
0.865 0.213 0.985 0.315
MCI, mild cognitive impairment; K-BNT, Korean-Boston Naming Test; RCFT, Rey Complex Figure test; COWAT, Controlled Oral Word Association Test; K-CWST, Korean-Color Word Stroop Test. Values are presented as mean 6 standard deviation. The statistical analysis between two groups was done by the t-test or Mann-Whitney test. *P<0.05.
Retrievaldeficit group
P value
23.3% 25.6% 5.6% 16.0%
26.7% 15.8% 0.0% 0.0%
>0.999 0.513 >0.999 0.290
MRI, magnetic resonance imaging; MCI, mild cognitive impairment; MTA, medial temporal atrophy; WMH, white matter hyperintensities. The statistical analysis between two groups was done by the Fisher’s exact test. P3-175
MCI, mild cognitive impairment; K-MMSE, Korean version of MiniMental State Examination; CDR, Clinical Dementia Rating; CDR-SB, CDR-sum of boxes. Values are presented as mean 6 standard deviation or as number (percentage) of patients. The statistical analysis between two groups was done by the t-test and chisquare or Fisher’s exact test. *P<0.05.
Retentiondeficit group
RELATIONSHIPS BETWEEN GLOBAL COGNITIVE DYSFUNCTION AND PET BIOMARKERS IN NORMAL AGING, MILD COGNITIVE IMPAIRMENT AND ALZHEIMER’S DISEASE
Eun Hyun Seo1, Dong Young Lee2, IL Han Choo2, Bo Kyung Sohn3, Jee Wook Kim4, Yu Kyeong Kim5, Eun Jin Yoon2, Jong Inn Woo2, 1Seoul National University, Seoul, South Korea; 2Seoul National University Hospital, Seoul, South Korea; 3Seoul National University, Seoul, South Korea; 4Department of Neuropsychiatry, Hallym University Hangang Sacred Heart Hospital, Seoul, South Korea; 5Seoul National University Bundang Hospital, Seongnam, South Korea. Background: Background: The relationship between Alzheimer’s disease (AD) pathological burdens and cognitive dysfunction still remain unclear. This study aimed to investigate the relationships of global cognitive dysfunction with cerebral beta-amyloid beta (burden and synaptic dysfunction, measured by [11 C]-labeled Pittsburgh Compound B (PiB)-positron emission tomography (PET) and [18 F] fluorodeoxyglucose (FDG)-PET, respectively, in cognitively normal (CN), mild cognitive impairment (MCI) and AD dementia. Methods: Twenty nine cognitively normal (CN) elderly, 30 subjects with mild cognitive impairment (MCI), and 26 with AD underwent clinical evaluation, PiB-PET and FDG-PET scanning. Two total scores (TS-l and TS-ll) of the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery (CERAD-NP) were calculated. Data were analyzed on a voxel-basis using statistical parametric mapping 2. Each TS was used as a covariate to find regions showing significant voxel-wise correlations (linear regression models adjusted for demographic influences). Results: For whole group, both TS showed negative correlations with Ab deposition in frontal and temporopaietal regions. Similarly, both TSs showed positive correlations with regional cerebral glucose metabolism (rCMglc) in frontal and temporopaietal regions. In CN, both TSs showed negative correlations with Ab deposition in left fusiform, left lingual gyrus, left inferior frontal gyrus and bilateral subcortical regions. TS-l showed positive correlations with rCMglc in left precuneus and right cuneus and TS-ll showed correlations in the slightly wider areas including bilateral parietal and frontal gyri and left temporal gyus. In regard of MCI, both TSs showed positive correlations with rCMglc in the bilateral frontal gyri and bilateral thalamus, whereas no correlation between each TS and Ab deposition was found. For AD, TS-l showed positive correlations with rCMglc in right inferior temporal gyrus and TS-ll showed correlations in bilateral inferior temporal gyri, whereas any correlation between each TS and Ab deposition was not found. Conclusions: Our results suggest that although both cerebral Ab burden and synaptic dysfunction have close relationships with general cognition, each of them probably makes differential contributions to cognitive decline according to the cognitive subgroups. P3-176
CONTROVERSIES OF NEUROBIOLOGICAL CORRELATES OF APATHY IN ALZHEIMER’S DISEASE: A SYSTEMATIC REVIEW
Florindo Stella1, Marcia Radanovic2, Ivan Aprahamian3, Sergio Hototian4, Michelle Ljubetic5, Larissa Andrade6, Orestes Forlenza7, 1UNESP -
Poster Presentations: P3 University Estadual Paulista, Biosciences Institute, Rio Claro, Sao Paulo, Brazil; 2Laboratory of Neurosciences - FMUSP, S~ao Paulo, Brazil; 3 Institute of Psychiatry - Hospital das Clınicas da FMUSP, S~ao Paulo, Brazil; 4Laboratory of Neurosciences, Sao Paulo, Brazil; 5Laboratory of Neurosciences, University of Sao Paulo, Brazil; 6UNESP - University Estadual Paulista, Rio Claro, Sao Paulo, Brazil; 7Laboratory of Neurosciences - FMUSP, S~ ao Paulo, Brazil. Background: Apathy has been reported as the most common neuropsychiatric syndrome in patients with Alzheimer’s disease (AD) with prevalence of 55-70%. Despite high prevalence, neurobiological correlates seem to be controversial. Dysfunction in frontal, temporal or parietal cortex, and basal ganglia have been mentioned in several studies involving structural and functional neuroimaging on apathy in AD. The aim of this study was to analyze neurobiological correlates of apathy in AD based on evidences of the literature involving structural or functional neuroimaging and classical AD biomarkers. Methods: We made a systematic review of publications, which included association between apathy in AD and structural (MRI, CT, DTI) or functional (PET, SPECT, spectroscopy) neuroimaging, and classical AD biomarkers (allele epsilon 4, APOE, beta-amyloid, neurofibrillary tangles). Results: We found 66 articles (27 were inserted in our analysis; 39 were excluded). The 27 publications were divided into two parts: brain neuroimaging (23 studies); and brain neurobiological biomarkers (5 studies). One study was involved in both parts. Frontal region was the most focused structure (17 studies) involving ortibofrontal, middle, and dorsolateral areas. Anterior cingulate (12 studies) was the second emphasized region, followed by temporal (7 studies), basal ganglia (7 studies), and parietal region (4 studies). Three investigations found no correlation between apathy and brain regions. More than one region was analyzed in the same study. Cognitive processes were correlated with specific brain regions. For instance, dysfunction of frontal areas have been linked to decline in planning and decision making, which are crucial for organizing and behavior performance. Disturbances of anterior cingulate were related to loss of motivation, loss of goaldirected behavior, and emotional blunting. Hypoactivity of basal ganglia was connected with decrease of dopaminergic process and loss of motor performance in motivated behavior. Atrophy of Meynert nucleus was linked to cholinergic and cognition decline, related to cognitive support for motivated behavior. Conclusions: Despite frontal regions (associated with planning and decision making) and anterior cingulate (related to emotional blunting and loss of motivation) have been considered crucial structures associated with apathy in AD, the results from studies remain controversial.
P3-177
COMBINING CLASSICAL CONDITIONING AND BRAIN-STATE CLASSIFICATION FOR THE DEVELOPMENT OF A BRAIN-COMPUTER INTERFACE (BCI) FOR ALZHEIMER’S PATIENTS
Giulia Liberati1, Ralf Veit2, Josue Dalboni da Rocha3, Sunjung Kim2, Dorothee Lule4, Christine von Arnim4, Antonino Raffone5, Marta Olivetti Belardinelli5, Niels Birbaumer2, Ranganatha Sitaram2, 1 Interuniversity Centre for Research on Cognitive Processing in Natural and Artificial Systems, Rome, Italy; 2Institute of Medical Psychology and Behavioral Neurobiology, Eberhard Karls-University, T€ubingen, Germany; 3 Institute of Medical Psychology and Behavioral Neurobiology, Eberhard Karls-University, T€ ubingen, Germany; 4Neurophysiology - Department of Neurology, University of Ulm, Ulm, Germany; 5Interuniversity Centre for Research on Cognitive Processing in Natural and Artificial Systems, Rome, Italy. Background: Alzheimer’s Disease (AD) patients who have lost the ability to communicate verbally may benefit from a Brain-Computer Interface (BCI), which could allow them to convey basic thoughts and emotions, e.g. by associating affirmative and non-affirmative thinking to a positive and a negative emotion, respectively. One possibility to develop a BCI that can be used with AD patients is to modulate brain responses with a se-
P515
mantic classical conditioning paradigm, in order to associate congruent and incongruent word pairs with emotionally positive and negative stimuli, facilitating the discrimination between “affirmative” and “non-affirmative” thinking. Using a classical conditioning paradigm is convenient, since it does not require AD patients to put active effort in learning how the BCI works. Methods: In our classical conditioning paradigm, already tested on 11 healthy subjects, the unconditioned stimuli consist of a positive and negative emotional sound (a baby laugh and a scream, respectively). The conditioned stimuli, presented aurally, are congruent (e.g. ’fruit-apple’) and incongruent (e.g. ’fruit-dog’) word pairs. During the conditioning acquisition, congruent and incongruent word pairs are associated to the baby laugh and the scream respectively. Functional magnetic resonance imaging (fMRI) will be performed on AD patients (Mini Mental State Examination score: 18-24; intact auditory system) on a 3T scanner. To classify the signals corresponding to congruent and incongruent word pairs, both univariate (General Linear Model) and multivariate (Support Vector Machine, SVM) analyses will be performed. Results: Both univariate and multivatiate analyses on healthy subjects confirmed the possibility to discriminate between affirmative and non-affirmative responses. We hypothesize that a similar differentiation may be found in AD patients, since classical conditioning was demonstrated to be possible, at least to some extent, in these patients.The study with AD patients is ongoing, and preliminary results will be presented during the conference. Conclusions: The encouraging results obtained with healthy subjects show that basic affirmative/non affirmative thinking discrimination is possible within an fMRI-BCI setting. The development of a BCI for AD patients could be an important step for allowing not only basic communication, but possibly lending a path for rehabilitation and diagnosis.
P3-178
ASSOCIATION BETWEEN DEPRESSIVE SYMPTOMS, COGNITIVE DECLINE, AND WHITE MATTER INTEGRITY IN COGNITIVELY NORMAL ADULTS WITH A FAMILY HISTORY OF ALZHEIMER’S DISEASE
Grace Lee1, Katie Smith2, Lori Holleran2, Ahra Ko3, George Bartzokis3, Po-Haong Lu3, 1UCLA Easton Center for Alzheimer’s Disease Research, Los Angeles, California, United States; 2Pepperdine, Los Angeles, California, United States; 3UCLA, Los Angeles, California, United States. Background: Depression is frequently observed in patients with Alzheimer’s Disease (AD) and has been shown to predict higher rates of progression from mild cognitive impairment (MCI) to AD. The neurobiological mechanism underlying this relationship may be related to white matter breakdown, which has been independently associated with both depression and AD. The current study examined the relationship between depressive symptoms, decline in processing speed, and white matter integrity on diffusion tensor imaging (DTI) in a high-risk sample of cognitively normal adults with a family history of AD. Methods: 51 subjects (29 males) from the UCLA Alzheimer’s Disease Research Center with a family history of AD who were cognitively normal at baseline with at least 2 follow-up visits were included in the present study. Subjects ranged in age from 47 to 88 years (mean¼66.1, sd¼8.5). Correlation analyses between baseline scores on the Geriatric Depression Scale (GDS), change in cognitive processing speed (CPS: WAIS-III Digit Symbol, Trails A) from baseline to 2-year follow-up, and DTI measures of white matter integrity were computed. Binary logistic regression was used to determine the association between GDS and conversion to amnestic MCI. Results: Baseline GDS scores were negatively correlated with change in CPS over 2 years (r ¼ -0.314, p¼.025). In a subset of subjects (n¼21) who underwent magnetic resonance imaging, GDS was also significantly correlated with fractional anisotropy (r ¼ -0.484, p¼.026) and marginally correlated with radial diffusivity (r ¼ 0.388, p¼.082) in frontal white matter. Both relationships indicate higher scores on the GDS were associated with reduced white matter integrity. In the entire sample, GDS was a significant predictor of conversion to MCI (p¼.015), even after controlling for age, years of education, and gender. Conclusions: Depressive