cognitive performance was demonstrated in demented and depressed pa- tients after 60 months of integrated therapy (Bragin V et al., 2012). Here we present the results of our ongoing, naturalistic study, in the same outpa- tient setting, at 72 months of treatment. Methods: 70 Patients (43 females, 27 males, mean age of 71.4 6 5.94, education - 13.00 6 2.69 with mild to moderate dementia and depression, with multiple chronic medical co- morbidities (hypertension, coronary artery disease, hyperlipidemia, dia- betes, arthritis etc.) underwent integrative treatment which consisted of pharmacological therapy (cholinesterase inhibitors, NMDA antagonists, an- tidepressants, along with their regular medication regimen) and non-phar- macological interventions. The non-pharmacological modalities included office and home-based physical and cognitive exercises aimed at the modi- fication of regional cerebral blood flow. Diet modifications, vitamins, and nutritional supplements were incorporated as well. Cognitive testing was performed annually and included the MMSE, clock drawing test, verbal fluency tasks, and the Neurobehavioral Cognitive Status Examination (Cog- nistat), Ruff 2 & 7 Selective Attention and Ruff Figural Fluency tests. Descriptive and non-parametric statistical analysis (Wilcoxon signed-rank test) was performed on SPSS for Windows, version 21.0. Results: Perfor- mance on all cognitive tests remained at or improved from their baseline for a period of 72 months. The baseline MMSE was 26.8 6 7.09 and by 72 months of the treatment, MMSE was 27.6 6 6.50 (p > 0.05). Significant improvement (p < 0.05) was observed on Cognistat orientation, attention, construction and memory subtests. Conclusions: The integrative treatment approach postponed cognitive decline in demented and depressed patients with multiple medical co-morbidities for 72 months. Future investigations addressing integrated treatment in AD are warranted. P4-104 INVOLVEMENT OF ANTERIOR AND POSTERIOR MEDIAL TEMPORAL LOBE NETWORKS IN EARLY ALZHEIMER’S DISEASE Sandhitsu Das 1 , John Pluta 2 , Lauren Mancuso 1 , Dasha Kliot 1 , Paul Yushkevich 1 , David A. Wolk 1 , 1 University of Pennsylvania, Philadelphia, Pennsylvania, United States; 2 University of Pennsylvania, Philadelphia, Pennsylvania, United States. Contact e-mail: sudas@seas. upenn.edu Background: We present cortical thickness data in amnestic Mild Cognitive Impairment (a-MCI) patients showing atrophyin both anterior and posterior medial temporal lobe (MTL) networks and their correlations with molecular biomarkers.Recent work has described two dissociable networks associated with MTL structures: (1) a ’posterior MTL network’ including posterior MTL regions [hippocampal tail, parahippocampus(PHC)], posterior cingulate/ precuneus, and posterior lateral parietal regions and (2) an ’anterior MTL network’ comprising anterior MTL regions [hippocampal head and perirhinal cortex (PRC)], ventral and polar temporal lobe, and lateral orbitofrontal cortices (Nat Rev Neurosci 13:716-726, 2012). Alzheimer’s disease (AD) is often described as a neurodegenerative disease that, at a network level, most early and significantly affects the posterior default mode network (DMN), which is essentially the posterior MTL network. However, earliest appearance of neurofibrillary tangles in anterior MTL regions, such as PRC, suggests potential early involvement of the anterior MTL network. Here we study cortical atrophy in both networks and analyze their relationship with measurements of Ab and pTauin prodromal AD. Methods: We labeled four seed regions in anterior and posterior MTL: PRC and hippocampal head (anterior) and PHC and hippocampal tail (posterior). We used these seeds to map anterior and posterior MTL networks in older healthy controls (OHC) from a Penn cohort using resting-state functional MRI. Defined networks were used as ROIs to calculate mean cortical thickness in a subset of the ADNI2 subjects (37 OHC, 55 MCI) and compared across groups. Correlation of network thickness with CSF tau and Abwere explored in MCI. Results: Cortical thickness was significantly reduced in MCI not only within posterior MTL networks, but to a similar extent in anterior networks, defined by hippocampal head and PRC. Increased pTau was significantly correlated with greater thinning in both anterior and posterior networks, whereas lowerAb appeared to be somewhat more strongly correlated with the posterior network. Conclusions: The data presented here argue that atrophy in prodromal AD is not limited to posterior regions of the DMN, but also similarly to cortical regions functionally connected with anterior MTL, sites of earliest tangle pathology, perhaps consistent with models of network level transmission of disease. P4-105 ALTERED FMRI ACTIVATION PATTERN DURING VISUAL SCENE ENCODING IN AFFECTED AND NON-AFFECTED CARRIERS OF PSEN1 AND APP MUTATIONS John D. West 1 , Shannon Leigh Risacher 1 , Eileen M. Tallman 1 , Brenna C. McDonald 1 , Yang Wang 1 , Francine Epperson 1 , Jill Murrell 1 , Table 1 Columns 1-4: Mean thickness values in the anterior and posterior networks as defined by various MTL seeds. T-statistic and p-values for a group comparison is also included. Column 5-6: Correlation between pTau/Ab and thickness in the MCI group. P-values are in parentheses. Seed ROI for network OHC (N¼37) Thickness MCI (N¼55) Thickness Thickness OHC>MCI t(p) MCI pTau correlation r(p) MCI Ab correlation r(p) Left Hipp head 2.15 1.94 3.26 (0.0008) -0.32 ( 0.02) 0.25 (0.08) Right Hipp head 2.08 1.88 3.20 (0.001) -0.33 (0.02) 0.27 (0.06) Left PRC 2.29 2.07 3.33 (0.0006) -0.32 (0.03) 0.19 (0.17) Right PRC 2.27 2.05 3.31 (0.0007) -0.31 (0.03) 0.22 (0.14) Left Hipp tail 2.03 1.82 3.20 (0.001) -0.32 (0.02) 0.30 (0.03) Right Hipp tail 1.97 1.77 3.07 (0.001) -0.33 (0.02) 0.32 (0.02) Left PHC 2.17 1.95 3.29 (0.0007) -0.33 (0.02) 0.32 (0.03) Right PHC 2.19 1.96 3.30 (0.0007) -0.34 (0.02) 0.31 (0.03) Cortical regions belonging to anterior and posterior MTL networks defined in a separate cohort of OHC subjects. Magenta shows over lap of networks defined by both seeds. Poster Presentations: P4 P822