Poster Session P2: Diagnosis and Disease Progression - Neuroimaging $281 sections of patients with GSS showed numerous lesions stained with methoxy-XO4. The methoxy-XO4 staining was highly specific both in mice and humans, with no other structures being detected. Conclusions: Prion amyloid deposits can be successfully targeted in vivo using methoxy-XO4. Radiolabeled derivatives of Tbioflavin and Congo red are viable candidates for PET imaging ligands for the improved diagnosis of human prion diseases associated with amyloid deposition. Supported by research grants from NIH/NIA (AG20747, AG202245) and Alzheimer's Association. •P2-]• HIPPOCAMPAL AMYGDALAL BRAIN AND CHANGES IN YOUNG-OLD AND VERY-OLD WITH ALZHEIMER'S DISEASE: ASSOCIATIONS WITH NEUROPSYCHOLOGICAL FUNCTIONING Nikki R. Home* 1,2, Mark W. Bondi 2,3, Christine Fennema-Notestine L3 , Wes S. Houston 3, Greg G. Brown 2,3, Terry L. Jernigan 2,3 , David E Salmon 4, Laura B. Mickes 5 , Brace Fischl 6'7 . The Human Brain Morphometry B1RN, www.nbirn.net, La Jolla, CA, USA; 1SDSU/UCSD Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA; 2 UCSD Department of Psychiatry, La Jolla, CA, USA; 3 VASDHS, San Diego, CA, USA; 4UCSD Department of Neuroscience, La Jolla, CA, USA; SUCSD Department of Psychology, La Jolla, CA, USA; 6Department of Radiology, Harvard Medical School, Charlestown, MA, USA; 7 MIT Artificial Intelligence Laborato(y, Massachusetts Institute of Technology, Cambridge, MA, USA. Contact e-mail: nhorne@ucsd.edu Background: Structural and functional decline associated with normal aging has led some investigators to suggest that less Alzheimer's disease (AD) pathology may be needed to produce pathologic cognitive decline in the Very-Old compared to the Young-Old (Terry et al., 1999). Bondi et al. (2003) recently reported that, when AD patients are compared to their age-appropriate control groups, the profile of neuropsychological deficits associated with AD in the Very-Old is less severe from that in the Young- Old. Objective: To assess possible interactions between age and disease on smactural decline, we examined volumes of smactures affected early in AD: the hippocampus and the amygdala. Method: Seventy-six individuals were assigned to one of four groups based on age and diagnosis: (1) Young-Old NC and AD groups included individuals ages 70 or younger, and (2) Very-Old AD and NC groups comprised of individuals ages 75 or greater. Results: The two AD groups significantly differed on raw volumes and their respective age-corrected z-scores for both the hippocampus (p = 0.004) and the amygdala (p = 0.031); Very-Old AD demonstrated significantly more atrophy (mean hippocampus z-score = -2.08; mean amygdala z- score = -1.92) relative to Young-Old AD (mean hippocampus z-score = -1.18; mean amygdala z-score = -1.32). However, these findings differed from their neuropsychologicai performances. Specifically, we found that the two AD groups significantly differed on their age-corrected z-scores on tests of memory (all ps < 0.001) in the opposite direction, with Very- Old AD performing significantly better than Young-Old AD relative to their age-appropriate normal control groups, despite significantly greater atrophy relative to their control group. Conclusions: Results suggest future research is needed to refine the pattern of deficits expected in the Very-Old and to validate such deficits with imaging techniques. In addition, these results do not support the hypothesis that less AD pathology is needed to evince comparable cognitive deficits in the Very-Old compared to the Young-Old. However, future volumetric studies should further assess this question in other neocortical association areas. Supported by: NCRR P41- RR14075, R01RR16594-01A1, & M01RR00827 BIRN(www.nbim.net); MIND Institute; NIH/NIA P50AG05131, RO1 AG12674, & AG04085; and DVA Medical Research Service. Table 1. Demographics Young-Old NC Very-Old NC Young-Old AD Very-Old AD n 15 18 16 27 Age 60.40 (6.94) 78.61(3.17) 64.31(4.98) 78.19 (2.27) Education 14.80 (2.62) 15.33 (3.50) 14.88 (2.50) 13.30 (3.98) DRS Total Score 140.00 (3.19) 140.53 (2.35) 109.75(17.14) 108.36(17.09) ~ LABELING AMYLOID PLAQUE-LIKE STRUCTURES BY RADIOIODINATED LIGANDS IN RHESUS MONKEY BRAIN Catherine Hou .1 , Mei-Ping Kung 1, yan Xin 1 ' Daniel M. Skovronsky 1, Robert Mach a, Hank E Kung 1. 1 University of Pennsylvania, Philadelphia, PA, USA; 2Washington University, St Louis, MO, USA. Contact e-mail: chou@sunmac.spect.upenn.edu Background: The deposition of ~3-amyloid (AI3) plaques is a hallmark of Alzheimer's disease (AD). We have previously developed and characterized several iodinated ligands, which specifically bind to Af3 plaques in AD and transgenic mouse (Tg) brains. Aged rhesus monkey brains have been shown through immuno- and thioflavin-staining to contain these plaques. While there are many similarities between monkey and human plaque characteristics, differences exist such as a higher proportion of AI3 40 over 42 in monkey. Objective(s): Radioiodinated ligands were used to detect Af3 plaques in aged monkey brains and the results were compared with the detection of plaques in AD and transgenic mouse brain sections. Methods: Various iodinated ligands were incubated with brain sections from rhesus monkey, transgenic mouse over-expressing A~, or human AD to visualize plaque staining. An emulsion autoradiogram was compared to thioflavin-stained and A[3 40 and 42 antibody labeled sections to confirm binding specificity. Results: Three radioiodinated ligands - K01-042, IMPY (label plaques containing AI3 40 and 42) and IMSB (predominately labels plaques containing AI3 40) - were used for the studies. All these ligands showed distinct labeling in monkey brain sections. Antibodies for A[3 40 and 42 confirmed the specific labeling of A[3 plaques and noted a general co-localization pattern of A[3 40 and 42 plaques. These ligands also labeled AI3 plaques in Tg mouse brains with a strong, uniform signal, while human plaque labeling sensitivity varied with the radioiodinated ligands from case to case. Conclusions: Aged rhesus monkey brains do contain AI3 plaque deposition, which is detectable by radioiodinated ligands. However, the nature of the plaques may be different from and do not have the heterogeneity of human AD cases. Therefore, aged monkeys may be a potential Alzheimer's animal model, but as with transgenic mice, the resuks may not be translated directly to AD in humans. • COMPARISON OF FMRI ACTIVATION PATTERNS IN MILD COGNITIVE IMPAIRMENT (MCI) SUBJECTS AND ELDERLY CONTROLS AT ULTRA-HIGH FIELD STRENGTH Sriyesh Krishnan* 1,2, Melissa J. Slavin 3,2, Thanh-Thu Tran 3,2, Lakshmi Murty 3,2, Anne E. Finefrock 4, EM. Doraiswamy 4, Jeffrey R. Petrella 2, t Duke University School of Medicine, Durham, NC, USA; 2Department of Radiology, Duke University Medical Center, Durham, NC, USA; 3Brain Imaging and Analysis Center, Duke University Medical Center, Durham, NC, USA; 4Department of Psychiatry, Duke University Medical Center, Durham, NC, USA. Contact e-mail: krishO05 @ mc.duke, edu Background: The MCI population represents a group of at-risk subjects who may have a prodromal form of AD. Analysis of functional brain activation differences in this population may aid in development of a technique for early diagnosis of AD. Objective(s): To assess differences in brain activation patterns between MCI subjects and elderly controls using fMRI at 4T during a memory encoding and retrieval task. Methods: Sixteen subjects (8 MCI, 8 controls) were studied during performance of a face-name memory encoding and retrieval task. The paradigm involved the presentation of novel face-name pairs and familiar face-name pairs within a blocked design. Statistical Parametric Mapping (SPM) random effects analysis using ANCOVA, with age as the covariate, was employed for comparison of the MCI group (5 male/3 female subjects, mean age 77.9, SD 6.1 years) and the control group (5 male/3 female subjects, mean age 74.5, SD 6.0 years). Volume of interest (VOI) analysis was carried out using a memory-specific VOI including the hippocampus, parahippocampal gyms, entorhinal and perirhinaI cortices, and an attention-specific VOI including the anterior cingulate gyms, dorsolateral prefrontal cortex, and superior