Normal controls Amnestic MCI converted to AD Amnestic MCI nonconverted to dementia p-value Age-Related White Matter Changes score 1.62.1 2.32.8 3.72.8 0.112 APOEe4, carriers --- 5 (56%) 6 (43%) 0.441 We processed SPECT images with SPM2 following an optimized protocol and performed a voxel-based statistical analysis comparing amnestic MCI patients converted to AD and non-converted to dementia vs controls, setting p-value at 0.001 uncorrected for multiple comparisons, setting the extent threshold at 100 voxels, using proportional scaling and entering age as a nuisance covariate. Results: In comparison with normal controls, amnestic MCI patients who converted to AD showed hypoperfusion in the right parahippocampal gyrus and in the left inferior temporal and fusiform gyri (figure A), whereas amnestic MCI patients who did not convert to dementia showed hypoperfusion in the retrosplenial cortex, precuneus and occipital gyri, mainly on the left side (figure B). Conclusions: Parahip- pocampal and inferior temporal hypoperfusion in amnestic MCI patients appears as a predictor of conversion to AD; hypoperfusion in the retro- splenial cortex is involved in memory impairment but does not seem the key finding of convertion to dementia. MONDAY, JUNE 11, 2007 ORAL O2-04 INTERVENTION AND TREATMENTS 2 O2-04-01 RISK FOR ALZHEIMER’S DISEASE IN DOWN SYNDROME IS RELATED TO CHOLESTEROL LEVEL AND STATIN USE Warren B. Zigman 1 , Nicole Schupf 1,2 , Edmund C. Jenkins 1 , Tiina K. Urv 3 , Benjamin Tycko 2 , Wayne Silverman 4 , 1 NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA; 2 The Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, NY, USA; 3 National Institute of Child Health and Human Development, Bethesda, MD, USA; 4 Kennedy Krieger Institute and Johns Hopkins University School of Medicine, Baltimore, MD, USA. Contact e-mail: warren.zigman@omr.state.ny.us Background: Studies suggest that increased total cholesterol levels (TC) are related to increased risk for Alzheimer’s disease (AD), and that statin use may reduce this risk, but results have been inconsistent. We examined this issue for adults with Down syndrome (DS), a population at high risk for AD. Objective: The high incidence and earlier age at onset of AD in the population with DS provides an unique opportunity to examine the hypothesis that increased TC levels are related to an increased risk of AD, and that statin use may decrease risk of AD. Methods: We used survival models to compare cumulative incidence of AD as a function of TC level and statin use at baseline in 123 adults with DS, adjusting for covariates. TC level was obtained from medical records. Dementia status was deter- mined based upon serial assessments of cognitive, adaptive and maladap- tive behavior, and a comprehensive review of medical records (plus neu- rological examinations for differential diagnosis). Results: Participants with TC  200 mg/dL were more than two times as likely to develop AD than subjects with TC  200 mg/dL [Hazard Rate (HR) = 2.6, p = .03]. Further, participants with TC levels  200 mg/dL who used statins had less than half the risk of developing AD than participants with TC levels  200 mg/dL who did not use statins (HR = .4, p = .05, one-tailed). Conclu- sions: This study provides evidence for the importance of cholesterol metabolism as a mediator of AD risk. The protective effect of statin use on risk of AD among participants with high cholesterol levels and high risk for AD parallels positive findings from observational studies in the general population. Recent data suggest a cholesterol-independent action of statins and inhibition of beta-amyloid deposition in the brain may be one possible pathway mediating the relationship between statin use and AD risk. Statins also have anti-inflammatory and antioxidant properties that may afford some protection. Supported by NIH grants R01-AG014763, P01-HD35897, R01-AG07232, R01-37425, the National Down Syndrome Society and NYS through its Office of Mental Retardation and Developmental Disabilities. O2-04-02 LIPITOR’S EFFECT IN ALZHEIMER’S DEMENTIA (LEADE) STUDY: BASELINE CHARACTERISTICS Roy Jones 1 , Rachelle Doody 2 , D. Larry Sparks 3 , Howard Feldman 4 , Miia Kivipelto 5 , Andrei Breazna 6 , Mindy Sovel 6 , David DeMicco 6 , Judith Hey-Hadavi 6 , On behalf of the LEADe Investigators 7 , 1 The Research Institute for the Care of the Elderly, Bath, United Kingdom; 2 Baylor College of Med/Neur, Houston, TX, USA; 3 Sun Health Research Institute, Sun City, AZ, USA; 4 University of British Columbia, Vancouver, BC, Canada; 5 Karolinska Institutet, Stockholm, Sweden; 6 Pfizer Inc, New York, NY, USA; 7 Multiple Centers, Various Countries including, NY, USA. Contact e-mail: r.w.jones@bath.ac.uk Background: Elevated cholesterol may influence the development and progression of Alzheimer’s Disease (AD) as it modulates the processing of amyloid precursor protein to amyloid beta peptide. Preliminary clinical data suggest that lowering cholesterol with a statin could potentially slow the symptomatic progression of AD. Objective(s): The LEADe study tests the hypothesis that adding a statin (atorvastatin 80 mg) to a cholinesterase inhibitor (donepezil 10 mg) benefits cognition and global functioning more than donepezil 10 mg alone in patients with mild-moderate AD. Methods: This is an international, multicenter (100 sites), double-blind, randomized (1:1), parallel-group study in patients with mild-moderate AD (n=641). Inclusion criteria are: men and women aged 50-90 years, MMSE 13-25, stable donepezil 10 mg for at least 3 months, and LDL-C 95-195 mg/dL. Co-primary endpoints are changes in Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and Alzheimer’s Disease Cooper- ative Study-Clinical Global Impression of Change (ADCS-CGIC) Scale scores. Sample size and power calculations are based on the ADCS-CGIC to detect a 30-40% difference in scores at 18 months. Results: Enrollment of 641 subjects is completed. The mean baseline data (SD) include: age, 74 (+/-8) years; sex, 53% females; MMSE, 21 (+/-3); ADAS-Cog, 32 (+/- 11); Alzheimer Disease Functional Assessment (ADFACS), 13 (+/-9); and Neuropsychiatric Inventory (NPI), 10 (+/-11). Prior duration of donepezil treatment was 409 (+/-407) days and Hachinski score was 0.6 (+/-0.76). Laboratory values include: total cholesterol, 227 (+/-33) mg/dL, LDL-C, 140 (+/-25) mg/dL, triglycerides, 137 (+/-65) mg/dL, HDL-C, 64 (+/-17) S192 Oral O2-04-01: Intervention and Treatments 2