- Email: [email protected]
P2-201: ER stress is associated with phosphorylation of tau in the pathology of Alzheimer's disease and Pick's disease
Poster Presentations P2: atrophy in whom the first symptom was a massive short term memory deficit (encoding deficit of visual and verbal sequences). This deficit mimics the “re´ponse a` coˆte´” (Ganser, 1898). Methods: 32 patients were included : a) 16 patients with a “Ganser-like” syndrome (GL group, mean age ⫽ 58 years ⫾ 6; mean MMSE ⫽ 16.9 ⫾ 3,7) and b) 16 patients with typical AD (AD group; mean age ⫽ 70 years ⫾ 9; mean MMSE ⫽ 18.8 ⫾ 2.3). The MMSE score was not different between groups (p ⫽ 0.19). The neuropsychological performance and the perfusion profile (SPECT - 99m Tc) of both groups were compared. Results: All patients of GL group presented with parietal symptoms. Gestural apraxia was the most frequent symptom (94% of patients), followed by simultagnosia and acalculia (88%). Between the two groups, working memory test performance was significantly different, both in verbal and visual modalities: 6,4 (⫾ 1.89) for the GL group and of 9.9 (⫾1.65) for the AD group for verbal and visual direct spans and 4 (⫾ 1.89) for the GL group and of 7.3 (⫾1.3) for the AD group for verbal and visual indirect spans. In the Grober and Buschke memory test which assesses long term episodic memory, the GL group had a lower encoding capacity than the AD group (p ⬍ 0.0001): 4,39 (⫾ 3.94) versus 9.12 (⫾ 2.39), respectively. The comparison of SPECT data showed a more severe hypoperfusion in parietal regions in GL group, with a more severe deficit in the left hemisphere in 11 out of 16 patients. Conclusions: Severe short term memory deficit, resembling a pseudopsychiatric disorder, can be observed as an early sign of degenerative process in young patients. This clinical presentation is similar to the “re´ponse a` coˆte´” observed in Ganser’s syndrome. This symptomatology is associated with parietal atrophy. This new presentation is important to recognize and underlines the role of parietal regions in working memory process, as it has already been demonstrated by functional imaging studies. P2-199
THE EFFECTS OF BILATERAL SUBTHALAMIC NUCLEUS DEEP BRAIN STIMULATION ON COGNITION IN PARKINSON’S DISEASE
Jae-Hyeok Heo1, Min Ky Kim1, Jin Young Ahn1, Tai Hwan Park1, Kyoung-Min Lee2, Sun Ha Paek2, Beom S. Jeon2, 1Seoul Medical Center, Seoul, Republic of Korea; 2Seoul National University Hospital, Seoul, Republic of Korea. Contact e-mail: [email protected] Background: The long term effects of subthalamic nucleus (STN) stimulation on cognition and mood have not been well established. The authors estimated the cognitive and mood effects of bilateral subthalamic nucleus deep brain stimulation (STN DBS) in patients with Parkinson’s disease (PD) at 6 months and 1 year postoperatively. Methods: Forty-six patients were recruited from the Movement Disorder Center at Seoul National University Hospital. Neuropsychologic tests were performed three times, before, 6 months after, and 1 year after surgery. Mean patient age was 58 and mean education duration eight years. Eighteen of the 46 patients were men.The instruments used for assessing cognitive functions were; the Mini-Mental Status Examination (MMSE), the Trail Making Test (TMT), the Korean Boston Naming Test (K-BNT), the Rey-Kim Memory Battery, the Grooved pegboard test, the Stroop test, a fluency test, the Wisconsin Card Sorting test (WCST), and the Beck depression inventory (BDI). Results: Of these tests, the verbal memory test, the Stroop test, and the fluency test showed statistically significant changes. The verbal memory test using the Rey-Kim memory battery showed a decline in delayed recall and recognition at 6 months and one year postoperatively, whereas nonverbal memory showed no meaningful change. In terms of frontal lobe function tests, Stroop test and fluency test findings were found to be aggravated at 6 months and this continued at 1 year postoperatively. Previous studies have consistently reported a reduction in verbal fluency and improvements in self-reported symptoms of depression after STN DBS. However, in the present study, Beck depression inventory (B.D.I.) was not significantly changed. Other tests, namely, MMSE, TMT, K-BNT, Grooved pegboard test, and the WCST also failed to show significant changes. Of the baseline characteristics, age at onset, number of years in
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full-time education, and L-dopa equivalent dosage were found to be correlated with a postoperative decline in neuropsychological test results. Conclusions: In conclusion, bilateral STN DBS in Parkinson’s disease did not lead to a significant global deterioration in cognitive function. However, our findings suggest that it has minor detrimental long-term impacts on memory and frontal lobe function. P2-200
THE EFFECT OF DEPRESSION LEVEL AND DEPRESSION FACTORS ON COGNITIVE FUNCTION IN NEUROPSYCHIATRIC PATIENTS
Baik Seok Kee1, Woong Hahm2, Young Cheul Eun1, Hyun Ju Cho1, 1 Chung-Ang University Hospital, Seoul, Republic of Korea; 2Keyo Hospital, Uiwang, Republic of Korea. Contact e-mail: [email protected] Background: To evaluate the depression patterns of patients visiting our dementia clinics and their effects on the cognitive function and the activity of daily living. Methods: The patients were given brain MRI, neurological examination, the Seoul neuropsychological screening battery, the geriatric depression scale(GDS) and the activity of daily living scale (ADL). Results: The depression rate of Alzheimer patients was the highest compared with other group. However, the vascular dementia showed the highest depression level. The results of factor analysis for the GDS were classified 4 factors such as depression, worry, dysphoria, and apathy. The depression factor of GDS was related to the attention, immediate visual recall, and executive function. On the other hand, the apathy factor were related to the core symptoms of dementia. Conclusions: It is important to ensure that the dementia patients need appropriate managements of depression through the evaluation of depression elements, as well as an treatment of dementia. P2-201
ER STRESS IS ASSOCIATED WITH PHOSPHORYLATION OF TAU IN THE PATHOLOGY OF ALZHEIMER’S DISEASE AND PICK’S DISEASE
Diana A. T. Nijholt1, Elise S. van Haastert2, Annemieke J. Rozemuller2, Rob Zwart1, Frank Baas1, Jeroen J. Hoozemans2, Wiep Scheper1, 1Amsterdam Medical Centre, Amsterdam, The Netherlands; 2VU University Medical Centre, Amsterdam, The Netherlands. Contact e-mail: [email protected] Background: The unfolded protein response (UPR) is a protein quality control mechanism that protects cells against endoplasmatic reticulum (ER) stress. Previous studies in our group and others have demonstrated involvement of the UPR in Alzheimer’s disease (AD). UPR markers (e.g. Bip and pPERK) were found in pre-tangle neurons containing hyperphosphorylated tau. In this study we demonstrate activation of the UPR in an other tauopathy, Pick’s disease (PiD), suggesting a causal role between UPR activation and tau hyperphosphorylation. Methods: Immunohistochemistry was used to assay the accumulation of tau and the activation of the UPR in post-mortem brain tissue derived form patients with sporadic PiD. Specific antibodies for phosphorylated tau, tau isoforms and UPR proteins were used on hippocampus, frontal cortex and temporal cortex from PiD, AD and nondemented control cases. Results: Our data indicate a connection between activation of the UPR and phosphorylation of tau. Activation of the UPR was observed in neurons in PiD and AD. In PiD, UPR activation markers were associated with neurons containing Pick bodies. Concomitantly with the accumulation of tau in astrocytes in PiD we also observed activation of the UPR in these cells, a phenomenon not observed in AD. Conclusions: Our data suggest a causal connection between activation of the UPR and tau phosphorylation in both AD and PiD. These observations suggest UPR activation might be an important mechanism in the development of tauopathies.
THE EFFECTS OF BILATERAL SUBTHALAMIC NUCLEUS DEEP BRAIN STIMULATION ON COGNITION IN PARKINSON’S DISEASE
Jae-Hyeok Heo1, Min Ky Kim1, Jin Young Ahn1, Tai Hwan Park1, Kyoung-Min Lee2, Sun Ha Paek2, Beom S. Jeon2, 1Seoul Medical Center, Seoul, Republic of Korea; 2Seoul National University Hospital, Seoul, Republic of Korea. Contact e-mail: [email protected] Background: The long term effects of subthalamic nucleus (STN) stimulation on cognition and mood have not been well established. The authors estimated the cognitive and mood effects of bilateral subthalamic nucleus deep brain stimulation (STN DBS) in patients with Parkinson’s disease (PD) at 6 months and 1 year postoperatively. Methods: Forty-six patients were recruited from the Movement Disorder Center at Seoul National University Hospital. Neuropsychologic tests were performed three times, before, 6 months after, and 1 year after surgery. Mean patient age was 58 and mean education duration eight years. Eighteen of the 46 patients were men.The instruments used for assessing cognitive functions were; the Mini-Mental Status Examination (MMSE), the Trail Making Test (TMT), the Korean Boston Naming Test (K-BNT), the Rey-Kim Memory Battery, the Grooved pegboard test, the Stroop test, a fluency test, the Wisconsin Card Sorting test (WCST), and the Beck depression inventory (BDI). Results: Of these tests, the verbal memory test, the Stroop test, and the fluency test showed statistically significant changes. The verbal memory test using the Rey-Kim memory battery showed a decline in delayed recall and recognition at 6 months and one year postoperatively, whereas nonverbal memory showed no meaningful change. In terms of frontal lobe function tests, Stroop test and fluency test findings were found to be aggravated at 6 months and this continued at 1 year postoperatively. Previous studies have consistently reported a reduction in verbal fluency and improvements in self-reported symptoms of depression after STN DBS. However, in the present study, Beck depression inventory (B.D.I.) was not significantly changed. Other tests, namely, MMSE, TMT, K-BNT, Grooved pegboard test, and the WCST also failed to show significant changes. Of the baseline characteristics, age at onset, number of years in
T429
full-time education, and L-dopa equivalent dosage were found to be correlated with a postoperative decline in neuropsychological test results. Conclusions: In conclusion, bilateral STN DBS in Parkinson’s disease did not lead to a significant global deterioration in cognitive function. However, our findings suggest that it has minor detrimental long-term impacts on memory and frontal lobe function. P2-200
THE EFFECT OF DEPRESSION LEVEL AND DEPRESSION FACTORS ON COGNITIVE FUNCTION IN NEUROPSYCHIATRIC PATIENTS
Baik Seok Kee1, Woong Hahm2, Young Cheul Eun1, Hyun Ju Cho1, 1 Chung-Ang University Hospital, Seoul, Republic of Korea; 2Keyo Hospital, Uiwang, Republic of Korea. Contact e-mail: [email protected] Background: To evaluate the depression patterns of patients visiting our dementia clinics and their effects on the cognitive function and the activity of daily living. Methods: The patients were given brain MRI, neurological examination, the Seoul neuropsychological screening battery, the geriatric depression scale(GDS) and the activity of daily living scale (ADL). Results: The depression rate of Alzheimer patients was the highest compared with other group. However, the vascular dementia showed the highest depression level. The results of factor analysis for the GDS were classified 4 factors such as depression, worry, dysphoria, and apathy. The depression factor of GDS was related to the attention, immediate visual recall, and executive function. On the other hand, the apathy factor were related to the core symptoms of dementia. Conclusions: It is important to ensure that the dementia patients need appropriate managements of depression through the evaluation of depression elements, as well as an treatment of dementia. P2-201
ER STRESS IS ASSOCIATED WITH PHOSPHORYLATION OF TAU IN THE PATHOLOGY OF ALZHEIMER’S DISEASE AND PICK’S DISEASE
Diana A. T. Nijholt1, Elise S. van Haastert2, Annemieke J. Rozemuller2, Rob Zwart1, Frank Baas1, Jeroen J. Hoozemans2, Wiep Scheper1, 1Amsterdam Medical Centre, Amsterdam, The Netherlands; 2VU University Medical Centre, Amsterdam, The Netherlands. Contact e-mail: [email protected] Background: The unfolded protein response (UPR) is a protein quality control mechanism that protects cells against endoplasmatic reticulum (ER) stress. Previous studies in our group and others have demonstrated involvement of the UPR in Alzheimer’s disease (AD). UPR markers (e.g. Bip and pPERK) were found in pre-tangle neurons containing hyperphosphorylated tau. In this study we demonstrate activation of the UPR in an other tauopathy, Pick’s disease (PiD), suggesting a causal role between UPR activation and tau hyperphosphorylation. Methods: Immunohistochemistry was used to assay the accumulation of tau and the activation of the UPR in post-mortem brain tissue derived form patients with sporadic PiD. Specific antibodies for phosphorylated tau, tau isoforms and UPR proteins were used on hippocampus, frontal cortex and temporal cortex from PiD, AD and nondemented control cases. Results: Our data indicate a connection between activation of the UPR and phosphorylation of tau. Activation of the UPR was observed in neurons in PiD and AD. In PiD, UPR activation markers were associated with neurons containing Pick bodies. Concomitantly with the accumulation of tau in astrocytes in PiD we also observed activation of the UPR in these cells, a phenomenon not observed in AD. Conclusions: Our data suggest a causal connection between activation of the UPR and tau phosphorylation in both AD and PiD. These observations suggest UPR activation might be an important mechanism in the development of tauopathies.