Background: Alzheimer’s disease (AD) is multi-dimensional in nature, characterized not only by cognitive and functional decline, but neuropsy- chiatric symptoms that develop commonly and are associated with consid- erable morbidity. These include agitation, aggression and psychosis, which often co-occur and have a particularly high persistence rate. Objectives: This trial represents a novel design and new clinical trials methodology to address whether emergence of agitation and/or psychosis can be delayed by agents that have psychotropic as well as possible neuroprotective proper- ties. Methods: This NIA-ADCS conducted trial is a randomized, placebo- controlled, double blind, multicenter, two-year trial of low-dose (10mg/ kg/d) sodium valproate therapy in 300 outpatients with mild to moderate AD who lacked agitation and psychosis at baseline. Participants have been followed on a regular basis with clinic visits as well as telephone contacts providing assessments of behavior, cognition, function, safety and tolera- bility. Valproate was selected because of its possible symptomatic efficacy for agitation in AD, known safety profile in numerous clinical samples, and because of recent preclinical and basic science evidence supporting its neuroprotective potential in AD. The primary hypothesis is that chronic valproate administration to patients with AD who lack agitation and psy- chosis at baseline will delay the emergence of agitation and/or psychosis. An effect of this kind may have significant public health implications, for instance, by delaying institutionalization or maintaining health-related quality of life. An important secondary hypothesis is that chronic valproate therapy will attenuate clinical progression of AD, measured by reduced cognitive or functional decline. In addition, safety and tolerability of chronic low-dose therapy will be addressed. Biological specimens are being obtained to study markers selected for their relevance to the disease as well as the postulated mechanism of action of valproate. A subset of participants is undergoing repeated MRI scans to address possible volu- metric changes associated with treatment. After the double-blind phase, there will be a two-month single-blind placebo-controlled washout phase to address possible emergence of psychopathology that previously might have been suppressed by active therapy. Results: Enrollment for the trial was completed in December, 2006. Conclusions: This represents a novel ap- proach to secondary prevention of psychopathology associated with AD. P-206 PIOGLITAZONE MODULATES PLASMA LEVELS OF -AMYLOID IN GLUCOSE INTOLERANT OLDER ADULTS G. Stennis Watson 1,2 , Pattie S. Green 2 , Laura D. Baker 1,2 , Kristoffer W. Rhoads 1,2 , Brenna A. Cholerton 1,2 , Mark A. Reger 2 , Dana A. Belongia 1 , Mark A. Fishel 1,2 , Steven E. Kahn 1,2 , Stephen R. Plymate 1,2 , Helen K. Chea 2 , Pankaj D. Mehta 3 , Suzanne Craft 1,2 , 1 VA Puget Sound HCS, Seattle, WA, USA; 2 University of Washington, Seattle, WA, USA; 3 Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA. Contact e-mail: gswatson@u.washington.edu Background: Peroxisome proliferator-activated receptor- (PPAR) ago- nists improve insulin sensitivity in persons with type 2 diabetes (T2DM), preserve cognition in persons with Alzheimer’s disease (AD), and modu- late -amyloid (A) levels in vitro, in animals, and in persons with AD. In contrast, insulin secretagogues, which are also used to treat T2DM, are not known to affect A levels. Objective(s): To compare the effects of the PPAR agonist pioglitazone and the insulin secretagogue nateglinide on plasma A levels in glucose intolerant older adults. Methods: Participants underwent a 2-h oral glucose tolerance test and were classified as glucose intolerant (i.e., impaired glucose tolerant or diabetic, conditions often associated with insulin resistance) based on 2-h plasma glucose levels (2-hpg) 140 mg/dl (n = 76; mean[SD]: age = 74.7[5.8] y, 2-hpg = 200.0 [40.8] mg/dl) or healthy (n = 26; age = 73.0[5.4] y, 2-hpg = 114.9[15.9] mg/dl). Glucose intolerant participants were randomized to a 4-month course of pioglitazone (30 mg daily), nateglinide (120 mg, 3 times daily), or placebo. Treatment groups did not differ significantly with respect to age or baseline 2-hpg. Blood was acquired at baseline for all participants and at month 4 for treated subjects. Results: Baseline A levels (combined across A species) were higher in glucose intolerant than healthy partici- pants (p=0.027). For healthy controls, higher glucose-stimulated insulin levels were associated with lower A40 levels (p=0.007) and greater A42-to-A40 ratio (p=0.001). For glucose intolerant adults, treatment with pioglitazone increased A40 levels, relative to placebo (p=0.036) or nateglinide (p=0.068). In contrast, pioglitazone decreased A42 levels (p=0.042) and the A42-to-A40 ratio (p=0.009), whereas neither nateg- linide nor placebo had a significant effect on these measures. At month 4, A42 levels were positively correlated with 2-hpg (p=0.013) and glyco- sylated hemoglobin (p=0.019) levels in glucose intolerant adults, indicat- ing that A42 levels rise as glucoregulation declines. Conclusions: These results support the notions that glucose intolerance is associated with elevated plasma A levels and that treating glucose intolerance can mod- ulate plasma A40 and A42 levels. In light of evidence associating diabetes and hyperinsulinemia with AD, treatment with PPAR- agonists and other strategies that improve glucose tolerance (and possibly insulin sensitivity) may reduce the risk for AD, in part, through modulation of A. P-207 COGNITIVE IMPROVEMENT AFTER STOPPING ANTICHOLINERGIC MEDICATIONS FOR URINARY INCONTINENCE Syed Zaidi, Joshua Shua-Haim, Avraham Tuvy, Dorina Hajnaj, Paul Lee, Mid Atlantic Geriatric Association, Jersey Shore University Medical Center, Ocean Medical Center, Manchester, NJ, Ocean, NJ, USA. Contact e-mail: avtuvy@gmail.com Background: Many elderly patients who suffer from cognitive impairment are treated with anticholinergic medications for urinary incontinence. Some of those patients are also treated with medications for dementia. Objec- tive(s): Investigate cognitive adverse event of anticholinergic medications used to treat urinary incontinence. Methods: New patients in our practice who were evaluated for memory loss & cognitive decline and were treated with oxybutinin or tolterodine tatrate were included in the study. At baseline (first office visit) and after three weeks after stopping medication, MMSE, ADL and IADL outcomes were assessed and recorded. Caregivers were asked regarding tolerability, adverse events and clinical impression regarding any noticeable cognitive or behavioral change. No other change of medications and dosing were done during the evaluation period. Re- sults: A total of 28 patients were evaluated. Two patients were excluded due to change in other medications during the evaluation time. Average age was 83.6. Average period of time patients were treated with oxybutynin or tolterodine tatrate was 13.6 months. Four patients restarted medication due to deterioration in urinary incontinence. Twenty two (22) patients were previously diagnosed with Alzheimer’s disease / dementia. Eighteen (18) patients were treated with medications for dementia. Average MMSE score at baseline was 14.7 (range 9 - 21). Average MMSE improved by 1.2 points after 3 weeks follow up. Fourteen caregiver / family member reported cognitive improvement. Better functional performance was also reported in one patient. Average ADL scores deterioration was 1.4 points during the follow up period mainly due to incontinence. There was no IADL change. Conclusions: Oxybutynin (Ditropen) and tolterodine tatrate (Detrol) treat- ment for urinary incontinence were associated with cognitive decline. Cognitive improvement was reported in 14 patients after stopping those medications. SUNDAY, JUNE 10, 2007 PLENARY PL1 PL1-01 LINKING PHYSICAL AND COGNITIVE HEALTH: THE IMPORTANCE OF PREVENTION Julie L. Gerberding, Centers for Disease Control, Atlanta, GA, USA. Contact e-mail: jgerberding@cdc.gov Abstract not available. S164 Plenary: PL1: Primary Risk and Prevention