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Poster Presentations: P3 fluency, a cognitive function mediated by late-myelinating association fibers known to be affected in AD. Methods: Demographically similar normal controls (NC; n¼15; age 77.5 6 4.0 yr), aMCI (n¼12; age 79.1 6 7.2 yr), and AD subjects (n¼14; age 78.3 6 9.6 yr) were recruited from the NYU AD center. DKI was performed on a 3T Trio MR system (Siemens), providing parametric maps of the diffusion metrics, including WMTI maps for D axon, AWF, D e,axial, and D e,radial 1,2. Parametric maps were transformed into a standard space, and the means were extracted for the metrics in both early-myelinating (EM) (i.e. posterior limb of internal capsule, cerebral peduncles) and late-myelinating (LM) tracts (i.e. sagittal stratum, superior longitudinal fasciculus)4. Mixed models were run. Results: Axonal density (i.e. AWF) declined in LM tracts in the AD course, but remained stable in EM tracts (interaction effect p<0.05 and withingroup main effect for tract type p<0.001). Myelin breakdown (i.e. D e,radial) in LM tracts worsened in the AD course, as well as in EM tracts but not until later stages of disease (interaction effect p ¼0.059 and withingroup main effect for tract type p<0.001). There was an interaction effect for D axon (p<0.05), but no main effects. No significant differences were found for D e,axial. Lower AWF and higher D e,radial were associated with increasing age. There was a partial correlation between D e,radial in LM tracts and verbal fluency r(38)¼-0.47, (p<0.01). Conclusions: These results using WMTI metrics parallel findings in DTI-based studies, but specify the WM microstructural changes that occur in the course of AD, and demonstrate their functional relevance. Our results highlight the importance of WM changes in addition to gray matter pathology in the study of AD. Future work with larger samples should verify these findings using a longitudinal design. 1 Fieremans E NeuroImage. 2011;58:177. 2 Fieremans E Novel WMTI sensitive to AD progression. AJNR. In press. 3 Bartzokis G. NBA. 2004;25:5. 4 Brickman AM NBA. 2012;33:1699. P3-127

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FORNIX WHITE MATTER DEGENERATION IS A SENSITIVE INDICATOR OF BOTH EARLY AND LATE COGNITIVE DECLINE IN A DIVERSE COMMUNITY COHORT

Evan Fletcher1, Philip Heubner2, Mekala Raman3, Dan Mungas4, Owen Carmichael1, Charles DeCarli5, 1University of California, Davis, Davis, California, United States; 2UC Davis, Davis, California, United States; 3Mayo Graduate School, Rochester, Minnesota, United States; 4UC Davis, Sacramento, California, United States; 5University of California at Davis, Sacramento, California, United States. Contact e-mail: [email protected] Background: A focus of recent research is to delineate the sequence of biological events leading from normal cognition to dementia. Numerous studies have investigated MRI measures (including white matter tract integrity, hippocampus volume, and brain volume) along with cognitive test scores, as predictors of clinical deterioration: from MCI to AD or normal to MCI. Recent work in our laboratory indicates that fornix white matter is a sensitive predictor for conversion from normal to MCI. Other recent work has shown that fornix and hippocampal changes accompany conversion from MCI to AD. But to our knowledge, few studies have compared the utility of these predictors for clinical deterioration of both normal and MCI subjects in the same cohort. Methods: 242 community-recruited subjects received baseline SENAS cognitive assessment and brain MRI. Separate Cox proportional hazards models were constructed for 190 baseline-normal subjects and 52 baseline-MCI subjects to identify predictors of clinical conversion within each group. The fornix body was delineated using warping to a template space and three tissue segmentation, the hippocampus was traced manually, and brain volume was calculated through automated tissue segmentation. Using a sequential model-building approach, we evaluated the volumes of the fornix body, hippocampus, and entire brain as MRI predictors, as well as cognitive measures of episodic memory and executive function. Nuisance predictors included age, years of education, and gender. Results: Over a mean follow-up period of 3.6 years for baseline normals and 2.8 years for baseline MCI, 38 baseline normal subjects converted to

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MCI or AD (36 to MCI), and 18 baseline MCI subjects converted to AD. In the normal group, fornix body volume and age were the only significant brain predictors of conversion. In the MCI group, fornix body volume and episodic memory significantly predicted conversion to AD. Hippocampus volume was not a significant predictor of either type of clinical conversion. Conclusions: Fornix white matter volume may be a sensitive biomarker of clinical deterioration across the spectrum from normal cognition to AD. White matter changes may therefore be a prominent feature of neurodegenerative disease at both early and late stages, as well as one of the few predictors of early impairment. P3-129

APOLIPOPROTEIN E ε-4 AFFECTS THE CORTICAL DECLINE IN ALZHEIMER’S DISEASE

Yeo Jin Kim1, Seun Jeon2, Hanna Cho3, Young Noh4, Geon Ha Kim5, Byoung Seok Ye4, Hee-Jin Kim6, Cindy Yoon7, Sung Tae Kim2, Sue J. Kang2, Jong-Min Lee8, Juhee Chin2, Sang Won Seo2, Duk L. Na2, 1 Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Seoul, South Korea; 2Samsung Medical Center, Seoul, South Korea; 3Departments of Neurology, Samsung Medical Center, Seoul, Republic of Korea, Seoul, South Korea; 4Samsung Medical Center, Seoul, South Korea; 5Department of Neurology, Samsung Medical Center, Sungyungwan University School of Medicine, Seoul, South Korea; 6Samsung Medical Center, Seoul, Seoul, South Korea; 7Department of Neurology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea; 8Department of Biomedical Engineering, Hanyang University, Seoul, South Korea. Contact e-mail: [email protected] Background: Apolipoprotein E epsilon 4 (APOE4)is a risk factor for the development of Alzheimer disease (AD) in later life. Previous cross-sectional MRI studies also suggested that APOE4 have an influence on brain structure. However, longitudinal study about the relationship between APOE4 and brain structure is rare. In this study, we examined that whether APOE4 affect the cortical decline over the course of 5 years. Methods: We prospectively recruited 35 patients with early stage of AD and 14 normal controls. The patients were classified in 2 groups according to APOE4 status: 19 APOE4 carriers and 16 APOE4 non-carriers. All subjects were assessed with neuropsychological tests and with magnetic resonance imaging (MRI) at baseline and Year 1, Year 3 and Year 5. We measured cortical thickness analysis using surface-based morphometry method of MRI. Mixed effects model were performed after possible confounders. Results: At baseline, there were no differences in the cortical thickness between APOE4 carriers and APOE4 noncarriers. Over five year follow up, however, APOE4 carriers showed significantly cortical decline in the bilateral parahippocampal gyri, superior temporal gyri, orbitofrontal cortices, left dorsolateral frontal cortex and right precuneus, compared to APOE4 non-carriers. Conclusions: Our findings suggest that APOE4 contribute to the acceleration of cortical decline in patients with AD. P3-130

FRACTIONAL ANISOTROPY DIFFERENCES IN ATTENTION AND DEFAULT MODE NETWORK AREAS BETWEEN HEALTHY AGING AND ALZHEIMER’S DISEASE

Angela Luedke1, Juan Fernandez-Ruiz2, Angela Tam1, Angeles Garcia1, Queen’s University, Kingston, Ontario, Canada; 2National University of Mexico, Distrito Federal, Mexico. 1

Background: Compared to healthy aging, Alzheimer’s disease (AD) patients show gray matter atrophy in the precuneus and posterior cingulate cortex (PCC), as well as functional disruption of the default mode network (DMN) and deficits in selective attention. In healthy aging, increased activation of the inferior frontal gyrus (IFG) during selective attention tasks suggests increased prefrontal cortex recruitment to maintain inhibitory functioning. Conversely, IFG activation is decreased in selective attention tasks in AD patients. White matter integrity is also frequently affected in AD, especially in frontal areas. We investigated differences in fractional anisotropy (FA), a measure of white matter integrity, within the precuneus, PCC and IFG in healthy controls (HC) and AD, which may help explain