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Imaging features of early stage of dementia with Lewy bodies
S788
Developing Topics: P4 Posters
disease is still not fully understood. In the present studies, the effect of nicotine on gastric myoelectrical activity (GMA) in Tg2576 mice, which overexpresses mutant human amyloid precursor proteins (hAPPS), was investigated. Methods: Female hAPPS and wild-type mice (6 month old, 20-25 g) were anaesthetised and surgically implanted with telemetry devices (PhysioTel Ò ETA-F20, Data Sciences International, U.S.A.) with recording wires sutured into the serosal side of the stomach. After 7 days recovery, animals were randomised to receive vehicle (saline 2ml/kg, i.p.) or nicotine (3mg/ kg, i.p.). Two hours of baseline GMA was recorded prior to drug/vehicle administration; recordings then continued for a further 6 h. Raw data were processed using Spike2 (Cambridge Electronic Design, U.K.) and analysed using a repeated measures 2-way ANOVA followed by Bonferroni t-tests. Results: The baseline dominant frequency (DF) of wild-type mice (n¼8) did not differ from that of hAPPS mice (n¼8): (6.6 6 0.8 counts per minute (cpm) v.s. 6.9 6 0.8 cpm, respectively, P>0.05). Saline had no effect on any of the parameters of the slow waves measured during the experiment (P>0.05). Nicotine reduced the DF gradually to 4.2 6 1.3 cpm (basal 6.6 6 0.8 cpm; P¼0.015, n¼5) in wild-type mice. The effects of nicotine lasted for 2 h before the DF shifted back to pre-nicotine levels. Nicotine failed to affect the DF in hAPPS mice (P>0.05) but transiently increased the % power of bradygastric range from 8.4 6 3.7% to 21.7 6 12.5% (P<0.05, n¼4). Conclusions: Whilst no differences in baseline GMA were detected between wild-type and hAPPS mice, the use of nicotine revealed subtle changes in the control of GMA. Further investigation of mechanisms controlling GMA in hAPPS mice may provide novel insights into the development of AD. P4-370
ADNI website (29/Feb/2012) for the following tests: Digit Span, Trail Making (TMT), WAIS Digit Symbol (DSST), Clock Drawing, Category Fluency, Boston Naming (BNT), Logical Memory (LMT) and Auditory Verbal Learning (AVLT). Analyses included repeated measures mixed modelling and effect size determination using Cohen’s d. Results: Data for up to 5 years were available for 226 non-demented controls aged 60 to 90 (mean age 76 years at onset). While the tests were able to differentiate the three cohorts extremely well; for the controls, no consistent pattern of decline was detected on any task over the study period. On the contrary, significant improvements occurred with repeated testing on most tests: eg AVLT (2 years), DSST (up to 2 years), TMT (up to 3 years), BNT & LMT (both up to 5 years). The effect sizes were in the small to large range: eg BNT (0.53 at 1 year), LMT immediate recall (0.72 at 3 years). Conclusions: Such training effects on neuropsychological tests have been previously reported (Wesnes & Pincock, 2002), while some computerised procedures, such as the CDR System, an integrated set of cognitive tasks designed specifically for, and used widely in longitudinal clinical trials, do not show practice effects after initial familiarisation. At this meeting (Wesnes et al), data are presented from the CDR System in a similar cohort to the ADNI Controls (256 non-demented individuals aged 70-90, mean 76), showing year-by-year declines over a 5-year period on comparable domains. Although the tests used in ADNI can reliably identify cognitive impairment, they will not prove useful in preclinical AD research.
IMAGING FEATURES OF EARLY STAGE OF DEMENTIA WITH LEWY BODIES
Chigusa Watanabe, Takako Makino, Hiroshimanishi Medical Center, Ootake, Hiroshima, Japan. Background: The neuroimaging findings in patients with mild cognitive impairment (MCI) associated with Alzheimer ’s disease (AD) or early stage of AD were well documented, as medial temporal atrophy on MRI, and temporoparietal and posterior cingulate hypometabolism on PET. In patients with Dementia with Lewy Bodies (DLB), the characteristic occipital cortical hypometabolism on PET was recognized. But it is still unclear the neuroimaging difference between AD and DLB in the early stages.The objective of this paper is to assess the neuroimaging characteristic on MRI and SPECT in early stages in DLB patients. Methods: We performed MRI examination (Siemens, MAGNETOM Harmony 1.5 T)in 17 cases of clinically probable DLB patientsM:F¼ 710, age 77.8 6 9.5 years, MMSE 246 3.36). Volumetric studies were performed to measure the hippocampal volumes. Visual rating was performed to measure the other areas including the midbrain. We examined single-photon emission computed tomography (SPECT) technetium-99m cysteinate dimmer (99m Tc-ECD) Toshiba, 7200DIand evaluated regional cerebral blood flow patterns using easy Z-score imaging system (eZIS) analysis. Results: Atrophy in medial temporal was relatively smaller than that of Alzheimer ’s disease. Atrophy in the midbrain was prominent in DLB patients. Less than half DLB patients showed hypoperfusion in occipital cortex on SPECT. Conclusions: We suggest that relatively small atrophy in medial temporal cortex, atrophy in the midbrain, hypoperfusion in the occipital cortex may be helpful in the diagnosis in the early stage of DLB. P4-371
THE NEUROPSYCHOLOGICAL TESTS USED IN ADNI WILL NOT PROVE USEFUL FOR CLINICAL TRIALS IN PRECLINICAL ALZHEIMER’S DISEASE
Keith Wesnes, Bracket Global, Goring on Thames, United Kingdom. Background: Recent research criteria for preclinical Alzheimer’s disease (AD) acknowledge the requirement for sensitive measures of ’psychomotor function’ to identify early clinical manifestations of AD (Sperling et al 2011). The Alzheimer’s Disease Neuroimaging Initiative (ADNI) employed eight widely used neuropsychological tests to identify the transition from normal aging to the earliest stages of memory loss through MCI/AD. The purpose of the present analysis was to determine the utility of the ADNI tests for repeated administration in preclinical AD research. Methods: Data from the Control, amnestic MCI and mild AD cohorts were downloaded from the
P4-372
EVIDENCE OF ALTERED TRKB PRE-MRNA SPLICING IN ALZHEIMER’S DISEASE
Jenny Wong1, Brett Garner2, Glenda Halliday3, John Kwok4, 1University of Wollongong, Wollongong, Australia; 2Illawara Health and Medical Research Institute, Wollongong, Australia; 3Neuroscience Research Australia, Randwick, Australia; 4Neuroscience Research Australia, Randwick-Sydney, Australia. Background: The mechanism(s) underlying brain-derived neurotrophic factor (BDNF) signaling dysfunction in Alzheimer’s disease (AD) are unknown. The BDNF receptor, tropomyosin receptor kinase B (TrkB) is the principal component of the BDNF signaling pathway. Recently, we reported elevated levels of the neuron-specific TrkB alternative transcript, TrkB-Shc, in the hippocampus of human AD brains and that its cellular overexpression negatively impacts BDNF signaling. In this current study, we determined how TrkB-Shc transcripts are increased in AD. Methods: We utilized human control/AD (n¼6/6) hippocampal brain tissue (Sydney Brain Bank, Australia). SHSY5Y neuronal cells were used in cell culture assays. A TrkB minigene was used to assess TrkB pre-mRNA splicing. Gene expression changes were measured by quantitative real-time PCR (mRNA) and western blotting (protein). Results: Utilizing a TrkB minigene transiently transfected into SHSY5Y cells, we
Developing Topics: P4 Posters
disease is still not fully understood. In the present studies, the effect of nicotine on gastric myoelectrical activity (GMA) in Tg2576 mice, which overexpresses mutant human amyloid precursor proteins (hAPPS), was investigated. Methods: Female hAPPS and wild-type mice (6 month old, 20-25 g) were anaesthetised and surgically implanted with telemetry devices (PhysioTel Ò ETA-F20, Data Sciences International, U.S.A.) with recording wires sutured into the serosal side of the stomach. After 7 days recovery, animals were randomised to receive vehicle (saline 2ml/kg, i.p.) or nicotine (3mg/ kg, i.p.). Two hours of baseline GMA was recorded prior to drug/vehicle administration; recordings then continued for a further 6 h. Raw data were processed using Spike2 (Cambridge Electronic Design, U.K.) and analysed using a repeated measures 2-way ANOVA followed by Bonferroni t-tests. Results: The baseline dominant frequency (DF) of wild-type mice (n¼8) did not differ from that of hAPPS mice (n¼8): (6.6 6 0.8 counts per minute (cpm) v.s. 6.9 6 0.8 cpm, respectively, P>0.05). Saline had no effect on any of the parameters of the slow waves measured during the experiment (P>0.05). Nicotine reduced the DF gradually to 4.2 6 1.3 cpm (basal 6.6 6 0.8 cpm; P¼0.015, n¼5) in wild-type mice. The effects of nicotine lasted for 2 h before the DF shifted back to pre-nicotine levels. Nicotine failed to affect the DF in hAPPS mice (P>0.05) but transiently increased the % power of bradygastric range from 8.4 6 3.7% to 21.7 6 12.5% (P<0.05, n¼4). Conclusions: Whilst no differences in baseline GMA were detected between wild-type and hAPPS mice, the use of nicotine revealed subtle changes in the control of GMA. Further investigation of mechanisms controlling GMA in hAPPS mice may provide novel insights into the development of AD. P4-370
ADNI website (29/Feb/2012) for the following tests: Digit Span, Trail Making (TMT), WAIS Digit Symbol (DSST), Clock Drawing, Category Fluency, Boston Naming (BNT), Logical Memory (LMT) and Auditory Verbal Learning (AVLT). Analyses included repeated measures mixed modelling and effect size determination using Cohen’s d. Results: Data for up to 5 years were available for 226 non-demented controls aged 60 to 90 (mean age 76 years at onset). While the tests were able to differentiate the three cohorts extremely well; for the controls, no consistent pattern of decline was detected on any task over the study period. On the contrary, significant improvements occurred with repeated testing on most tests: eg AVLT (2 years), DSST (up to 2 years), TMT (up to 3 years), BNT & LMT (both up to 5 years). The effect sizes were in the small to large range: eg BNT (0.53 at 1 year), LMT immediate recall (0.72 at 3 years). Conclusions: Such training effects on neuropsychological tests have been previously reported (Wesnes & Pincock, 2002), while some computerised procedures, such as the CDR System, an integrated set of cognitive tasks designed specifically for, and used widely in longitudinal clinical trials, do not show practice effects after initial familiarisation. At this meeting (Wesnes et al), data are presented from the CDR System in a similar cohort to the ADNI Controls (256 non-demented individuals aged 70-90, mean 76), showing year-by-year declines over a 5-year period on comparable domains. Although the tests used in ADNI can reliably identify cognitive impairment, they will not prove useful in preclinical AD research.
IMAGING FEATURES OF EARLY STAGE OF DEMENTIA WITH LEWY BODIES
Chigusa Watanabe, Takako Makino, Hiroshimanishi Medical Center, Ootake, Hiroshima, Japan. Background: The neuroimaging findings in patients with mild cognitive impairment (MCI) associated with Alzheimer ’s disease (AD) or early stage of AD were well documented, as medial temporal atrophy on MRI, and temporoparietal and posterior cingulate hypometabolism on PET. In patients with Dementia with Lewy Bodies (DLB), the characteristic occipital cortical hypometabolism on PET was recognized. But it is still unclear the neuroimaging difference between AD and DLB in the early stages.The objective of this paper is to assess the neuroimaging characteristic on MRI and SPECT in early stages in DLB patients. Methods: We performed MRI examination (Siemens, MAGNETOM Harmony 1.5 T)in 17 cases of clinically probable DLB patientsM:F¼ 710, age 77.8 6 9.5 years, MMSE 246 3.36). Volumetric studies were performed to measure the hippocampal volumes. Visual rating was performed to measure the other areas including the midbrain. We examined single-photon emission computed tomography (SPECT) technetium-99m cysteinate dimmer (99m Tc-ECD) Toshiba, 7200DIand evaluated regional cerebral blood flow patterns using easy Z-score imaging system (eZIS) analysis. Results: Atrophy in medial temporal was relatively smaller than that of Alzheimer ’s disease. Atrophy in the midbrain was prominent in DLB patients. Less than half DLB patients showed hypoperfusion in occipital cortex on SPECT. Conclusions: We suggest that relatively small atrophy in medial temporal cortex, atrophy in the midbrain, hypoperfusion in the occipital cortex may be helpful in the diagnosis in the early stage of DLB. P4-371
THE NEUROPSYCHOLOGICAL TESTS USED IN ADNI WILL NOT PROVE USEFUL FOR CLINICAL TRIALS IN PRECLINICAL ALZHEIMER’S DISEASE
Keith Wesnes, Bracket Global, Goring on Thames, United Kingdom. Background: Recent research criteria for preclinical Alzheimer’s disease (AD) acknowledge the requirement for sensitive measures of ’psychomotor function’ to identify early clinical manifestations of AD (Sperling et al 2011). The Alzheimer’s Disease Neuroimaging Initiative (ADNI) employed eight widely used neuropsychological tests to identify the transition from normal aging to the earliest stages of memory loss through MCI/AD. The purpose of the present analysis was to determine the utility of the ADNI tests for repeated administration in preclinical AD research. Methods: Data from the Control, amnestic MCI and mild AD cohorts were downloaded from the
P4-372
EVIDENCE OF ALTERED TRKB PRE-MRNA SPLICING IN ALZHEIMER’S DISEASE
Jenny Wong1, Brett Garner2, Glenda Halliday3, John Kwok4, 1University of Wollongong, Wollongong, Australia; 2Illawara Health and Medical Research Institute, Wollongong, Australia; 3Neuroscience Research Australia, Randwick, Australia; 4Neuroscience Research Australia, Randwick-Sydney, Australia. Background: The mechanism(s) underlying brain-derived neurotrophic factor (BDNF) signaling dysfunction in Alzheimer’s disease (AD) are unknown. The BDNF receptor, tropomyosin receptor kinase B (TrkB) is the principal component of the BDNF signaling pathway. Recently, we reported elevated levels of the neuron-specific TrkB alternative transcript, TrkB-Shc, in the hippocampus of human AD brains and that its cellular overexpression negatively impacts BDNF signaling. In this current study, we determined how TrkB-Shc transcripts are increased in AD. Methods: We utilized human control/AD (n¼6/6) hippocampal brain tissue (Sydney Brain Bank, Australia). SHSY5Y neuronal cells were used in cell culture assays. A TrkB minigene was used to assess TrkB pre-mRNA splicing. Gene expression changes were measured by quantitative real-time PCR (mRNA) and western blotting (protein). Results: Utilizing a TrkB minigene transiently transfected into SHSY5Y cells, we