Empathy and frontal behavioral patterns discriminate between vascular dementia, Alzheimer's disease and frontotemporal dementia

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in POC, hippocampus and insula between the two groups. Conclusions: In this study, we determined the morphological and functional changes in the brain areas most susceptible to AD pathology. We revealed that the reduction of BOLD response due to the disease in POC and hippocampus was much greater than the structural changes in the corresponding areas. These results indicate that olfactory fMRI can be a more sensitive marker for detection and evaluation of AD.

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Fig 1. Comparison of total volume and activation volume in hippocampus and POC between NC and AD groups.

Fig 2. Olfactory fMRI activation difference between AD and NC groups. One-tailed two sample t-test of NC to AD showed significant reduction in activation of AD in the hippocampus(A) and POC(B) areas. relationship of atrophy in central olfactory structures to their functional deficit in AD by quantitatively determine the relationship of olfactory fMRI activation with local atrophy in the POC and hippocampus. Methods: 12 AD and 20 age-matched normal controls (NC) participated in this study. All AD and NC participants completed the University of Pennsylvania Smell Identification Test (UPSIT). The anatomical and fMRI images were acquired using a 3T MRI scanner. The olfactory stimulation paradigm consisted of three concentrations (0.10%, 0.32% and 1.0%) of the odorant (lavender) administered sequentially with three repetitions for each concentration. Each odor stimulation lasted for 6s, followed by 42s of baseline with odorless air. The hippocampus and POC were manually segmented and were saved as ROIs for subsequent fMRI activation voxels in those two local regions. Results: The UPSIT scores were significantly different (21.17 6 7.94 for AD and 30.85 6 5.69 for NC). The volumes and activation voxels of POC and hippocampus are showed in Fig. 1,. The AD group showed prominent atrophy in both hippocampus and POC. Compared to NC group, the average volumes of the POC and hippocampus in the AD group were reduced by 39% and 44%. There was a high correlation between the atrophy of POC and hippocampus (p <0.001). Olfactory activations in the corresponding structures show a much greater reduction in AD: 98% in POC and 95% in hippocampus. The activation reduction and local atrophy in these two regions were significantly correlated (P ¼ 0.008 for POC and P ¼ 0.033 for hippocampus). Fig. 2 demonstrated olfactory fMRI activation difference

RELATIONSHIP BETWEEN CEREBRAL GLUCOSE METABOLISM AND [C-11]BF-227 ACCUMULATION IN THE STAGES FROM COGNITIVELY NORMAL TO ALZHEIMER’S DISEASE

Kengo Ito1, Kentaro Hatano1, Ken Fujiwara1, Akinori Nakamura1, Yukihiko Washimi1, Yutaka Arahata1, Hideyuki Hattori1, Kenji Yoshiyama2, Hisayuki Miura1, Nobuyuki Okamura3, Kazuhiko Yanai4, 1National Center for Geriatrics and Gerontology, Obu, Japan; 2Osaka University, Osaka, Japan; 3Tohoku University School of Medicine, Sendai, Japan; 4Tohoku University, Sendai, Japan. Background: [C-11] BF-227 (2-(2-[2-dimethylaminothiazol-5-yl]ethenyl)6-(2-[fluoro]ethoxy) benzoxazole) is a PET probe for detection of dense amyloid deposits, which has been developed in Tohoku University. The purpose of this study was to investigate change of glucose metabolism depending on BF-227 accumulation in cognitively normal subjects, subjective cognitive complaint (SCI), and amnestic mild cognitive impairment (aMCI). Methods: [C-11] BF-227 (2-(2-[2-dimethylaminothiazol-5-yl] ethenyl)- 6-(2-[fluoro]ethoxy) benzoxazole) is a PET probe for detection of dense amyloid deposits, which has been developed in Tohoku University. The purpose of this study was to investigate change of glucose metabolism depending on BF-227 accumulation in cognitively normal subjects, subjective cognitive complaint (SCI), and amnestic mild cognitive impairment (aMCI). Results: Slightly decreased metabolic area was detected in the precuneus in NLn4 and SMC compared to NLn11. In NLn11 and NLn15 the glucose metabolism in the precuneus was inversely correlated with mean cortical SUVR of BF-227. The mean cortical SUVR of BF-227 was inversely correlated with WMS-R logical memory I and II in NLn11. Conclusions: The results suggest that BF-227 binding corresponds to pathological and symptomatic progression in preclinical and prodromal stage. P4-371

EMPATHY AND FRONTAL BEHAVIORAL PATTERNS DISCRIMINATE BETWEEN VASCULAR DEMENTIA, ALZHEIMER’S DISEASE AND FRONTOTEMPORAL DEMENTIA

Suvarna Alladi, Sivaranjani Ch, Mekala Shailaja, Chadalawada Santhoshi, Richa Nigam, Subhash Kaul, Nizam’s Institute of Medical Sciences, Hyderabad, India. Background: Behavioral disturbances in social situations are common in dementia syndromes. Recent studies implicate impairment in empathy and frontal systems to account for these changes. We aimed to study empathy and frontal behavior in subtypes of dementia, i.e., Vascular Dementia (VaD), Alzheimer’s Disease (AD) and Frontotemporal Dementia (FTD) and look for patterns that could discriminate between them. Methods: Empathy was assessed in patients with VaD (n ¼ 15), AD (n ¼ 15) and FTD (n ¼ 14) by interviewing caregivers using Interpersonal Reactivity Index (IRI) adapted to Telugu speaking population, both before and after the onset of illness. Empathic Concern (EC) and Personal Distress (PD) subscales were used to assess emotional empathy, and Perspective Taking (PT) subscale was used to assess cognitive empathy. Behavioral evaluation was done with Frontal Systems Behavior Scale (FrSBe) within which three aspects were studied- apathy, disinhibition, and executive dysfunction. Results: The three groups of dementia subtypes were matched for dementia severity, education and gender. FTD patients had significant decline in all subscales of empathy (p < 0.002). PT score dropped significantly in VaD (p <0.0001) while there was no decline in any of the empathy scores in AD. There was an increase in total FrSBe and its subscale

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scores after onset of illness in all dementia subtypes. On covariate analysis, patients with FTD had a significant increase in total scores of FrSBe, disinhibition and executive dysfunction compared to AD and VaD. Worsening of apathy was to same extent in all subtypes. Conclusions: This study demonstrated specific patterns of impaired empathy and frontal behavior in dementia subtypes. Cognitive empathy declined in VaD while FTD patients demonstrated impairment of both cognitive and emotional empathy. AD patients showed no change in ability to empathise. Apathy, executive dysfunction and disinhibition were common in all three subtypes, however FTD had more severe impairment in executive dysfunction and disinhibition. P4-372

COGNITIVE INTERVENTION IN A VARIANT OF ALZHEIMER’S DISEASE: A CASE REPORT  Jorge Alves, Rosana Magalh~aes, Sara Cruz, Adriana Sampaio, Oscar Gonc¸alves, University of Minho, Braga, Portugal. Background: Some variants of Alzheimer’s disease (AD) have been previously identified and described in the literature. Despite the existence of a few studies describing the neuropsychological deficits present in atypical presentations, there is still sparse research on cognitive intervention in atypical presentations of AD. Methods: In this work we report the case of a 57 years old patient diagnosed with a variant of Alzheimer’s disease that presented to our services complaining about temporal disorientation, watching time and reading problems. After a neuropsychological assessment he was submitted to a cognitive intervention program which comprised two blocks of 15 sessions of 2 hours delivered 3 times a week. This cognitive rehabilitation program included exercises like identification of numbers, simple math operations, object naming exercises, clock exercises and providing strategies for orientation. The focus of the intervention was therefore to improve functionality and autonomy through direct retraining and compensation. We conducted neuropsychological assessments at the following moments: baseline, at the end of the first block, after the second block of the program and follow-up. Results: The neuropsychological assessment exhibited deficits in learning and memory (visual and verbal auditory) as well as visual perceptive and visual constructive abilities, and temporal disorientation. After the intervention small improvements in temporal orientation (with some clues), verbal learning and memory and psychomotor abilities were observed. Difficulties in sustained attention and severe deficits in visual constructive abilities were still evident. The patient reported being more confident and some differences in mood were noticed by patient’s significant others. 9 months after the intervention the patient was stable on measures of learning and memory. Conclusions: In accordance with the only previous published work on cognitive intervention in AD variants, we observed that this type of intervention can provide small improvements which are clinically relevant. Further studies should be carried out in order to systematically evaluate the potentialities of cognitive intervention in AD variants. P4-373

COGNITIVE INTERVENTION IN ALZHEIMER’S DISEASE: A TREATMENT OPTION TO CONSIDER?  Jorge Alves, Rosana Magalh~aes, Adriana Sampaio, Oscar Gonc¸alves, University of Minho, Braga, Portugal. Background: The major goal of cognitive intervention is to treat the cognitive deficits resulting from brain damage. This type of intervention has been used in the context of Alzheimer’s disease (AD), however there are still no definite conclusions about its efficacy and cost-effectiveness. These issues assume even more relevance if we consider the individual and societal costs of the disease. Methods: We reviewed recent literature in the field of cognitive intervention for people with AD. We explored data about efficacy and cost-effectiveness of this approach. Bibliometric and funding data were also collected. Results: Some of the studies showed improvements in participants’ cognition. There is a limited amount of data on cost-effectiveness. The number of published studies on cognitive intervention in AD is scarce when comparing with pharmacotherapy for cognitive symptoms in AD. However the ratios of high quality studies (i.e. randomized controlled trials) are similar. Search on comparative funding between cognitive intervention and pharmacotherapy pointed to a substantially superior funding for cogni-

tion therapies. Conclusions: Due to the scarcity of studies it is impossible to establish definite conclusions. Manual inspection of the obtained data on funding revealed unrealistic estimations due to search engine limitations, therefore these results are not considered. Even though the reviewed studies showed that there is little evidence to support the efficacy of cognitive intervention in AD, the largest RCT’s yielded improvements in cognition. Moreover specific cognitive interventions could enhance the effects of drug therapy and be more cost-effective than traditional treatment by itself. This assumption seems reasonable when we consider that cognitive intervention in older adults can reduce medical care expenditures. We therefore conclude that it is necessary to obtain a substantial body of evidence to settle this question. Future research should also systematically explore clinical significance, functionality outcomes, individual and societal costs when assessing the outcomes of the different cognitive interventions ultimately evaluating the capability of cognitive intervention to decrease the disease burden of AD. In addition, consensus about a neuropsychological assessment battery for use in clinical trials should be reached by a panel of experts. P4-374

YOUNG EXPANDED LESION THAN ELDER SINCE EARLY STAGE IN ALZHEIMER’S DISEASE

Chigusa Watanabe, Sadao Katayama, National Hospital Organization Hiroshima-Nishi Medical Center, Ootake, Japan. Background: Onset of Alzheimer’s disease is a wide age from a young age to old age, otherwise the age differences is not clear. Among patients with similar memory impairment, we clarify difference of the brain dysfunction and changes of them about 400 days after in different age groups. Methods: During April 2007 to March 2011, visited the clinic to forget things, forget without obvious pathological, motor dysfunction, hearing impairment and visual dysfunction in daily life, by receive the brain function tests (Rivermead behavioral memory test (RBMT), test of frontal assessment battery (FAB) and MMSE, the head MRI, showed no lesions other than the obvious brain atrophy, and SPECT (3D-SSP analysis) showed low perfusion in the posterior cingulate gyrus, parietal and temporal lobe, the patient was diagnosed with Alzheimer’s disease. Among them, the degree of memory impairment, MMSE 2 or 3 points/3 on word registration and standard profile score (SPS) of RBMT 0-4 points/ 24 in 530 patients among 55w85 years-old, SPS of RBMT for each three age group (A:55-65, B:66-75, C:76-85 age group) differences of the values of the each brain functional test were analyzed, statistically. Furthermore, the change of the value of the each test 400 days after re-examined was compared in each age group. Results: In the whole of the SPS, A group, B group, C group in the order, RBMT raw score, MMSE total score was significantly lower. FAB showed a similar trend. The re-examination after about 400 days, RBMT SPS, SS, MMSE any type, B, C were significantly lower than those in Group A. Conclusions: Early onset patient of Alzheimer’s disease revealed more intellectual dysfunction except memory dysfunction and showed more rapid progress rather than late onset patient in the same level of memory loss. P4-375

ACTION-INTENTIONAL SPATIAL BIAS IN A PATIENT WITH POSTERIOR CORTICAL ATROPHY

Jay Kwon1, Matthew Cohen2, Kenneth Heilman2, 1Department of Neurology, Changwon Fatima Hospital, Changwon, South Korea; 2 Department of Psychology, University of Florida, Gainesville, Florida, United States. Background: Patients without sensory neglect might demonstrate a spatial bias when drawing. Methods: To better understand the mechanism of this bias, we examined a 61 year-old woman with probable posterior cortical atrophy (PCA) who on imaging showed right hemisphere atrophy and dysfunction. Results: When drawing a clock she correctly made a circle but when writing the numbers deviated to the left. A blindfolded midsagittal plane pointing test revealed that her leftward directional bias was action-intentional rather than perceptual-attentional. Conclusions: This bias (ipsilateral intentional neglect) was made manifest by altering visual feedback such as having her focus her attention on the clock numbers.