Alzheimer’s Imaging Consortium IC-P: Poster Presentations Roger Gunn3, Vincenzo Libri3, J. John Mann1,2, Ramin V. Parsey1,2, 1Columbia University, New York, NY, USA; 2New York State Psychiatric Institute, New York, NY, USA; 3GlaxoSmithKline, London, United Kingdom. Contact e-mail:
[email protected] Background: The relative utility of the positron emission tomography (PET) radioligand N-methyl-11C-2-(4-methylaminophenyl)-6-hydroxybenzothiazole (also known as 11C-6-OH-BTA-1 or 11C-PIB) and 18F-fluorodeoxyglucose (18F-FDG) in distinguishing Alzheimer’s Disease (AD), mild cognitive impairment (MCI) and controls (CTR) is not fully established. Methods: Patients with mild AD (n ¼ 18), MCI (n ¼ 24) and CTR subjects (n ¼ 18) were studied. A diagnostic evaluation, neuropsychological tests, 11C-PIB PET, 18F-FDG PET, and structural MRI were done. For 11C-PIB, region of interest (ROI) binding potentials (BPND) from the Logan graphical method were obtained, using cerebellar reference. For 18F-FDG, regional cerebral metabolic rate for glucose (rCMRGlu) was obtained using an arterial input function. Results: The three subject groups (n ¼ 59) differed in 11C-PIB BPND in prefrontal cortex (p < .001), cingulate (p < .001), parietal cortex (p < .001), precuneus (p < .001) and parahippocampal gyrus (p < .004), but not hippocampus. These differences occurred in the AD-CTR and AD-MCI comparisons, with no significant differences between MCI and CTR. For 18F-FDG (n ¼ 51), rCMRGlu differed across the three groups in the precuneus (p ¼ 0.004) and parietal cortex (p ¼ 0.02). These differences occurred in the AD-CTR and AD-MCI comparisons, with no significant differences between MCI and CTR. Mean 11C-PIB BPND was higher in AD compared to CTR, and MCI compared to CTR. Mean 18F-FDG rCMRGlu did not differ among the groups. 11C-PIB BPND showed strong inverse correlations with cognitive test scores in prefrontal, cingulate, parietal and precuneus, but not hippocampus. 18F-FDG rCMRGlu showed less robust positive correlations with cognitive test scores, primarily in parietal cortex and precuneus. For each ROI, when both 11C-PIB BPND and 18F-FDG rCMRGlu were entered into logistic regression models, 11C-PIB BPND significantly differed between AD and CTR in prefrontal, cingulate, parietal and parahippocampal gyrus, and between AD and MCI in prefrontal, cingulate, parietal and precuneus. 18F-FDG rCMRGlu was not significant in these analyses. Conclusions: When evaluated simultaneously, 11C-PIB BPND but not 18F-FDG rCMRGlu had group discriminating ability. The ability of 11C-PIB PET to distinguish AD, MCI and CTR underlines its potential use in differential diagnosis, and patient selection and monitoring in treatment trials. IC-P-031
PIB NEGATIVE DEMENTIA: PITFALL OF CLINICAL DIAGNOSIS OF ALZHEIMER’S DISEASE
Hiroyuki Shimada1, Suzuka Ataka1, Jun Takeuchi1, Jyoji Kawabe1, Susumu Shiomi1, Hiroshi Mori1, Takami Miki1, Makoto Shigematsu2, Yasuhiro Wada2, Yasuyoshi Watanabe2, Aki Nakanishi3, 1Osaka City University Graduate School of Medicine, Osaka, Japan; 2Riken Center for Molecular Imaging Science, Kobe, Japan; 3Osaka Municipal Kohsaiin Hospital, Osaka, Japan. Contact e-mail:
[email protected] Background: Amyloid imaging have been utilized to detect the amyloid deposition in the brain. It has been reported that Alzheimer’s disease (AD) and some of MCI patients show deposition by the 11CPiB-PET. We have reported that there were some PiB negative dementia patients who were clinically diagnosed as AD. In this study, we evaluated the characteristics of these PiB negative patients. Methods: We examined PiBPET study for 44 dementia patients who suffered cognitive decline or memory disturbance. They were clinically diagnosed as AD with neurological and neuropsycological evaluations, laboratory tests. PiB binding was calculated using the Logan graphical analysis method to yield regional distribution volume ratio (DVR) with cerebellum as reference. The PiB-negative 10 patients (3 males and 7 females, 75.1 6 2.4 years old) were compared with 34 PiB-positive patients (13 males and 21 females, 73.3 6 7.4 years old). Cerebrospinal fluid (CSF) Ab40, 42, tau, p-tau levels were measured. MRI images were obtained in all patients to compare their brain morphology. Results: All patients were finally confirmed as AD with their neuropsycological features and met NINCDS-ADRDA criteria.
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There were no PiB negative patients who have ApoE 4 genotype. The CSF P-tau and tau levels were significantly decreased, and the CSF Ab1-42 levels was increased in PiB negative patients. We divided the PiB negative patients into four groups with the results of the CSF biomarkers, FDG-PET and brain MRI. Group 1 contained 4 patients who showed the unilateral atrophy of the medial temporal lobe. In group 2 patients, we found the atrophy and hypo glucose metabolisms in their frontal lobe. Group 3 includes only 1 patient who showed the increase of CSF ptau level as AD patients. We have 2 patients in group 4, and they showed no apparent features by the brain MRI and FDG-PET images. Conclusions: These results suggest that clinically diagnosed AD patients may include the non-AD type dementia (PiB negative dementia). Because neuropsychological features of these patients were consistent with AD patients, it is useful to separate these patients into different types of dementia utilizing PiB-PET, FDG-PET, brain MRI and CSF biomarkers for effective treatment. IC-P-032
ALZHEIMER’S DISEASE (AD) AND LEWY BODIES DEMENTIA (LBD) DIFFERENTIAL DIAGNOSIS: A 123IOFLUPANE SPECT STUDY
Susanna Nuvoli1, Antonio Nieddu2, Anthony Rotondo2, Renata Salvo2, Francesca Chessa1, Angela Spanu1, Giuseppe Madeddu1, 1Nuclear Medicine Dept., University of Sassari, Sassari, Italy; 2Geriatrics Dept., Policlinico Sassarese, Sassari, Italy. Contact e-mail:
[email protected] Background: To evaluate 123Ioflupane SPECT usefulness in LBD and AD differential diagnosis in patients with doubtful clinical criteria. Methods: We studied 39 consecutive patients, (20 Female; 19 Male), aged 52-84 yrs with cognitive disorders for 12-36 mths and with clinical criteria not distinguishable to differentiate AD (NINCDS ADR-DA) from LBD (LBD Consortium International Workshop). Parkinson’s disease was clinically excluded and CT/MRI were negative in all cases. All patients underwent brain SPECT, 3-4 hrs after 148 MBq 123Ioflupane (DaTSCANÒ, GE Healthcare Medical Diagnostic) i.v. injection. SPECT images were evaluated by both qualitative and quantitative analysis, the latter by a dedicated software (NEUROTRANS 3D; Segami Corp.) which quantifies specific striata dopaminergic activity expressed as Binding Potentials (BP) applying attenuation and partial volume effect corrections by a deformable 3D model segmentation generated by degrading Talairach atlas. Caudate and putamen BP cut-off of 3.3 was determined in 20 sex-age matched normal controls (mean values: 4,9 6 0,71 and 4,6 6 0,67 for caudate and putamen, respectively). Results: 123Ioflupane SPECT was qualitatively classified normal (N) in 28/39 (71.8%) patients and pathological (P) in 11/39 (28.2%). In N group BP was >3.3 in 56/56 (100%) caudate and in 53/56 (95%) putamen; it was
