amyloid deposition similar to AD. We also hypothesized that levels ofamyloid deposition and memory impairment are correlated. Methods:Thirty-one older subjects recruited from longitudinal studies of aging anddementia underwent neuropsychological assessment and PIB PET. Therewere 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) basedon the Buschke SRT memory scores adjusted for IQ. PET was acquiredover 60 minutes after injection of 10-15 mCi C11-PIB. PIB binding wascalculated using the Logan graphical analysis method in an aggregatedcortical 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 wassignificantly 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 in3 of 6 MCI, 4 of 8 IQ-MI, and 1 of 8 NC subjects; the remaining subjectshad low PIB retention (DVR � 1.0, non-specific binding). Among PIB-positive subjects, greater PIB binding was associated with poorer perfor-mance on the SRT memory scores (r�0.59, p�.01) and the Boston Nam-ing (r� 0.66, p� 0.001) test. Conclusions: Our findings support thehypothesis that a subset of highly intelligent adults with subtle memoryimpairment, who would otherwise be classified as normal, have amyloiddeposition. In addition, amyloid burden appears highly correlated withmemory and naming ability.

P2-330 ALTERED BRAIN IRON METABOLISM AS ARISK 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: wkirsch@llu.edu

Background: The role of increased brain iron in the pathogenesis ofAlzheimer’s Disease (AD) remains unsettled - is it causing oxidative stressor merely a bystander effort? Objectives: Two groups of elderly partici-pants - one cognitively intact and the other mildly cognitively impaired(MCI) - have been studied sequentially over the past 36 months bytechnologies to determine if altered brain iron metabolism constitutes a riskfor progressive neurodegeneration and AD. Methods: 28 control and 76MCI participants are studied by new minimally invasive magnetic reso-nance (MR) and ex vivo technologies to correlate changes in regional brainiron levels with detailed sequential psychometric evaluations. MR imagingincludes susceptibility weighted imaging (SWI), magnet prepared rapidacquisition gradient echo (MP-RAGE), fluid attenuated inversion recovery(FLAIR), and MR spectroscopy (MRS). SWI does not currently have FDAapproval, but is available to investigators with Institutional Review Boardpermission for experimental use. SWI has advantages over conventionalMR sequences for tissue iron estimation because of greater sensitivity andprecision. Regional brain iron levels determined by SWI are expressed inphase units � standard deviation. Blood RNA, proteomic, and flow cyto-metric studies assay iron metabolism parameters. Results: The controlgroup has remained cognitively stable over a 36 month period whereassignificant co-morbidity and cognitive decline have been noted in the MCIcohort. Fourteen MCI cases have become demented with confirmed se-quential hippocampal volume loss. SWI imaging gives quantitative andsensitive phase measures of regional brain iron with apparent enhancedsensitivity for non-invasively identifying amyloid angiography and micro-hemorrhages (5 of 14 progressively dementing MCI cases). FLAIR enablesestimation of white matter hyperdensities, indicative of small vessel dis-ease. Conclusions: This study is the first application of brain SWI fordocumenting changes in regional brain iron content and microhemorrhagesduring progressive dementia. MRS-detected changes in cingulate gyrusmetabolite levels associated with progressive dementias are consistent withprevious reports. We conclude that a uniquely monitored cohort of MCIindividuals at risk for progressive dementia yields valid statistical associ-

ations for predictor variables never before measured. This research wasfunded by NIH Grant #AG20948.

P2-331 DIFFERENTIAL EFFECTS OF WHITE MATTERLESIONS ON MEDIAL TEMPORAL LOBEATROPHY IN EARLY VERSUS LATE ONSETALZHEIMER’S DISEASE

Frank-Erik De Leeuw1, Wiesje van der Flier2, Esther Korf2,Frederik Barkhof2, Philip Scheltens2, 1UMC St Radboud, Nijmegen, TheNetherlands; 2VuMC, Amsterdam, The Netherlands. Contact e-mail:h.deleeuw@neuro.umcn.nl

Background: Alzheimer’s disease (AD) is usually diagnosed as a singledisease entity. However, there is much variation in clinical and radiologicalcharacteristics between early (� 65 years; EOAD) and late (�65 years;LOAD) onset AD. It has been postulated that EOAD is a primary neuro-degenerative disorder, while vascular factors leading to white matter le-sions (WML), are related with LOAD. Medial temporal lobe atrophy(MTA) is a key feature in both EOAD and LOAD, but this may have adifferent aetiology in the EOAD than in LOAD since in LOAD a relationbetween WML and MTA has been described. We hypothesized that WMLwould be related with MTA only in the LOAD and not in the EOAD.Objective: To investigate the relation between WML and MTA in EOADand LOAD. Methods: We investigated 179 ‘probable’ AD patients ac-cording to NINCDS-ADRDA criteria. All patients underwent 1T coronalT1- and transverse PD or FLAIR scanning. WML and MTA were ratedsemi-quantitatively with the ARWMC scale and the Scheltens’ scale,respectively. The relation between MTA and WML was assessed by ageand sex adjusted linear regression analysis for EOAD and LOAD sepa-rately. Adjustments were made for MMSE. Results: Mean age of theEOAD (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 was0.6 (SD2.2) and 1.5 (SD2.9) in the LOAD, p�0.2. Mean MTA in theEOAD was 1.3 (SD0.9) and 1.9 (SD1.0) in the LOAD, p�0.4.There wasa linear relation between the ARWMC grade and MTA (��0.09; 95%CI0.03-0.15), p�.006 in the LOAD, and not in the EOAD. In the LOADpatients 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 inEOAD vs LOAD. This may indicate that in the EOAD another, possiblyneurodegenerative process leads to MTA while in LOAD WML are relatedto MTA. This suggests heterogeneity in AD.

P2-332 NEUROPSYCHOLOGICAL TEST INALZHEIMER’S DISEASE WITH WHITE MATTERLESION

Jeong-Lan Kim, Dae-Ho Lee, Kyong-Ok Lim, Eun-Hee Sohn,Chungnam National University Hospital, Daejeon, Republic of Korea.Contact e-mail: kimjl@cnu.ac.kr

Background: The relationship between cerebral white-matter lesions andcognitive performance has been one of the most controversial issues. Someresearch showed poorer neuropsychological performance in AD patientswith severe WML than in those with mild WML. However, others showedno major differences on a broad neuropsychological battery. Objective(s):This study is aimed to evaluate any relationship between cerebral white-matter lesions and Camcog, which is one of the neuropsychological tests,in probable Alzheimer’s disease of NINCDS-ADRDA. Methods: Subjectsincluded 60 (men 17, women 43) patients. All subjects received brainmagnetic resonance scanning (B-MRI) and Camcog, which is a cognitivetest part of CAMDEX and is divided into 7 cognitive subsets, such asorientation, language, memory, attention/calculation, praxis, abstract think-ing, and perception. White matter changes in B-MRI were rated withManolio scale, ranged from 0 to 9. Results: AD patients with more severeWML have proorer neurocognitive function, especially orientation, lan-

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