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Poster P2:: Monday Posters

amyloid deposition similar to AD. We also hypothesized that levels of amyloid deposition and memory impairment are correlated. Methods: Thirty-one older subjects recruited from longitudinal studies of aging and dementia underwent neuropsychological assessment and PIB PET. There were 9 AD, 6 MCI, and 16 highly intelligent (AMNART mean IQ⫽127) CDR⫽0 subjects who were classified as NC (N⫽8) or IQ-MI (N⫽8) based on the Buschke SRT memory scores adjusted for IQ. PET was acquired over 60 minutes after injection of 10-15 mCi C11-PIB. PIB binding was calculated using the Logan graphical analysis method in an aggregated cortical region-of-interest comprising superior frontal, anterior cingulate, parietal, and precuneus, which yielded a distribution volume ratio (DVR) with cerebellar gray as reference. Results: Group mean PIB binding was significantly higher in AD than in MCI, IQ-MI, or NC groups (p⬍ .001). However, PIB binding within the range of AD (PIB-positive) was seen in 3 of 6 MCI, 4 of 8 IQ-MI, and 1 of 8 NC subjects; the remaining subjects had low PIB retention (DVR ⬃ 1.0, non-specific binding). Among PIBpositive subjects, greater PIB binding was associated with poorer performance on the SRT memory scores (r⫽0.59, p⬍.01) and the Boston Naming (r⫽ 0.66, p⬍ 0.001) test. Conclusions: Our findings support the hypothesis that a subset of highly intelligent adults with subtle memory impairment, who would otherwise be classified as normal, have amyloid deposition. In addition, amyloid burden appears highly correlated with memory and naming ability. P2-330

ALTERED BRAIN IRON METABOLISM AS A RISK FACTOR FOR ALZHEIMER’S DISEASE

Wolff M. Kirsch1, Floyd Petersen1, Mohammad Ayaz2, Ayaz Khan2, Ivan Kim1, Waheed Baqai1, Cindy Dickson1, Barbara A. Holshouser1, Udo Oyoyo1, Daniel Kido1, E. Mark Haacke2, 1Loma Linda University, Loma Linda, CA, USA; 2MRI Institute for Biomedical Research, Detroit, MI, USA. Contact e-mail: [email protected] Background: The role of increased brain iron in the pathogenesis of Alzheimer’s Disease (AD) remains unsettled - is it causing oxidative stress or merely a bystander effort? Objectives: Two groups of elderly participants - one cognitively intact and the other mildly cognitively impaired (MCI) - have been studied sequentially over the past 36 months by technologies to determine if altered brain iron metabolism constitutes a risk for progressive neurodegeneration and AD. Methods: 28 control and 76 MCI participants are studied by new minimally invasive magnetic resonance (MR) and ex vivo technologies to correlate changes in regional brain iron levels with detailed sequential psychometric evaluations. MR imaging includes susceptibility weighted imaging (SWI), magnet prepared rapid acquisition gradient echo (MP-RAGE), fluid attenuated inversion recovery (FLAIR), and MR spectroscopy (MRS). SWI does not currently have FDA approval, but is available to investigators with Institutional Review Board permission for experimental use. SWI has advantages over conventional MR sequences for tissue iron estimation because of greater sensitivity and precision. Regional brain iron levels determined by SWI are expressed in phase units ⫾ standard deviation. Blood RNA, proteomic, and flow cytometric studies assay iron metabolism parameters. Results: The control group has remained cognitively stable over a 36 month period whereas significant co-morbidity and cognitive decline have been noted in the MCI cohort. Fourteen MCI cases have become demented with confirmed sequential hippocampal volume loss. SWI imaging gives quantitative and sensitive phase measures of regional brain iron with apparent enhanced sensitivity for non-invasively identifying amyloid angiography and microhemorrhages (5 of 14 progressively dementing MCI cases). FLAIR enables estimation of white matter hyperdensities, indicative of small vessel disease. Conclusions: This study is the first application of brain SWI for documenting changes in regional brain iron content and microhemorrhages during progressive dementia. MRS-detected changes in cingulate gyrus metabolite levels associated with progressive dementias are consistent with previous reports. We conclude that a uniquely monitored cohort of MCI individuals at risk for progressive dementia yields valid statistical associ-

ations for predictor variables never before measured. This research was funded by NIH Grant #AG20948. P2-331

DIFFERENTIAL EFFECTS OF WHITE MATTER LESIONS ON MEDIAL TEMPORAL LOBE ATROPHY IN EARLY VERSUS LATE ONSET ALZHEIMER’S DISEASE

Frank-Erik De Leeuw1, Wiesje van der Flier2, Esther Korf2, Frederik Barkhof2, Philip Scheltens2, 1UMC St Radboud, Nijmegen, The Netherlands; 2VuMC, Amsterdam, The Netherlands. Contact e-mail: [email protected] Background: Alzheimer’s disease (AD) is usually diagnosed as a single disease entity. However, there is much variation in clinical and radiological characteristics between early (ⱕ 65 years; EOAD) and late (⬎65 years; LOAD) onset AD. It has been postulated that EOAD is a primary neurodegenerative disorder, while vascular factors leading to white matter lesions (WML), are related with LOAD. Medial temporal lobe atrophy (MTA) is a key feature in both EOAD and LOAD, but this may have a different aetiology in the EOAD than in LOAD since in LOAD a relation between WML and MTA has been described. We hypothesized that WML would be related with MTA only in the LOAD and not in the EOAD. Objective: To investigate the relation between WML and MTA in EOAD and LOAD. Methods: We investigated 179 ‘probable’ AD patients according to NINCDS-ADRDA criteria. All patients underwent 1T coronal T1- and transverse PD or FLAIR scanning. WML and MTA were rated semi-quantitatively with the ARWMC scale and the Scheltens’ scale, respectively. The relation between MTA and WML was assessed by age and sex adjusted linear regression analysis for EOAD and LOAD separately. Adjustments were made for MMSE. Results: Mean age of the EOAD (n⫽62) was 58.2 years of age (SD 4.0) and 73.6 (SD 5.1) in LOAD (n⫽117). There was no difference for MMSE between the groups (18.9 (SD5.0) vs. 20.9 (SD5.0), p⫽0.2). Mean ARWMC grade in the EOAD was 0.6 (SD2.2) and 1.5 (SD2.9) in the LOAD, p⫽0.2. Mean MTA in the EOAD was 1.3 (SD0.9) and 1.9 (SD1.0) in the LOAD, p⫽0.4.There was a linear relation between the ARWMC grade and MTA (␤⫽0.09; 95%CI 0.03-0.15), p⫽.006 in the LOAD, and not in the EOAD. In the LOAD patients with WML had significantly more MTA than those without (2.1 (SD0.9) vs 1.7 (SD 1.0), p⫽0.04). This was not found among EOAD. Conclusion: Our data show differential effects of WML on MTA in EOAD vs LOAD. This may indicate that in the EOAD another, possibly neurodegenerative process leads to MTA while in LOAD WML are related to MTA. This suggests heterogeneity in AD. P2-332

NEUROPSYCHOLOGICAL TEST IN ALZHEIMER’S DISEASE WITH WHITE MATTER LESION

Jeong-Lan Kim, Dae-Ho Lee, Kyong-Ok Lim, Eun-Hee Sohn, Chungnam National University Hospital, Daejeon, Republic of Korea. Contact e-mail: [email protected] Background: The relationship between cerebral white-matter lesions and cognitive performance has been one of the most controversial issues. Some research showed poorer neuropsychological performance in AD patients with severe WML than in those with mild WML. However, others showed no major differences on a broad neuropsychological battery. Objective(s): This study is aimed to evaluate any relationship between cerebral whitematter lesions and Camcog, which is one of the neuropsychological tests, in probable Alzheimer’s disease of NINCDS-ADRDA. Methods: Subjects included 60 (men 17, women 43) patients. All subjects received brain magnetic resonance scanning (B-MRI) and Camcog, which is a cognitive test part of CAMDEX and is divided into 7 cognitive subsets, such as orientation, language, memory, attention/calculation, praxis, abstract thinking, and perception. White matter changes in B-MRI were rated with Manolio scale, ranged from 0 to 9. Results: AD patients with more severe WML have proorer neurocognitive function, especially orientation, lan-