Adeline SL Ng, Amanda RJ Ng, Ivane Chew, Nagaendran Kandiah Department of Neurology, National Neuroscience Institute, Singapore APOE4 status modulates the impact of cerebral white matter disease on cognition in Alzheimer’s Disease BACKGROUND & OBJECTIVES.  We identified AD patients participating in research studies at the National Neuroscience Institute, Singapore having undergone APOE testing, MRI brain and cognitive battery consisting of the Mini-Mental State Exam (MMSE), Montreal Cognitive Assessment (MOCA), Frontal Assessment Battery (FAB) and Alzheimer’s Disease Assessment Scale (ADAS-11).  White matter hyperintensities (WMH) were quantified using the modified Fazekas scale (0-12) on T2-weighted MR sequence and medial temporal atrophy (MTA) was graded using the Scheltens scale (0-4) on coronal SPGR sequences. MRI rating was performed blinded to clinical and cognitive status.  We performed analysis of variance to evaluate the relationship between WMH and cognitive scores, and Spearman’s rank correlation analysis to determine the relationship between APOE4 status, degree of MTA, WMH load and cognitive scores. METHODS CONCLUSION RESULTS The authors report no conflicts of interest. Dr Adeline SL Ng National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore  The APOE4 allele has been established as a risk factor for Alzheimer’s disease (AD), but research into its association with cerebral ischemia has been inconsistent.  We determined to investigate white matter disease as a surrogate marker for cerebral ischemia and its relationship with APOE4 status and cognitive performance. 54 patients fulfilled the required criteria (Table 1): 17 had no WMH; 18 had mild WMH ; 19 had moderate-severe WMH  Patients with increasing WMH performed poorer on the MMSE, MOCA, FAB and ADAS-11  There was a significant correlation between poorer performance on colour-trail testing (p=0.021), digit cancellation (p=0.036) and category fluency (p=0.043) with higher WMH load  Geriatric Depression Scale scores were also associated with higher WMH (p=0.042)  WMH adversely influences cognitive function in AD.  APOE4 status modulates this association, with APOE4-negative patients demonstrating a strong correlation between WMH load and cognition while APOE4 positive patients having a weaker correlation.  This information would be useful in designing AD clinical trials as the modulatory effect of APOE4 would need to be considered. 18 patients tested positive for APOE4 (Tables 2 - 4):  APOE4 status did not significantly influence the correlation between MTA and cognitive scores, but influenced the correlation between WMH and cognition.  Correlation between poorer MOCA (r=-0.41; p=0.04) and FAB (r=-0.29;p=0.17) scores with greater WMH load was significant and approaching statistical significance respectively in the APOE4 negative group while the corresponding correlation was weaker in the APOE4 positive group. Table 1. Demographics, ApoE status and cognitive scores according to white matter severity No. of patients Mean Age (yrs)ApoE4+(%)ApoE2+(%)ApoE3+(%)% male Mean Edu (yrs) Mean MMSE Mean MOCA Mean ADAS-11Mean FABMean GDS WM absent WM mild-mod WM severe Table 2. Characteristics according to ApoE status No. of patients Mean Age (yrs)% male Mean Edu. (yrs) Mean MMSE ApoE 3/ ApoE 4/ ApoE 3/ ApoE 2/ ApoE 2/ Table 3. Cognitive Scores Stratified by ApoE4 and WMH status Variable ApoE4 –ve (n=35)ApoE4 +ve (n=18) WMH Absent N=8 WMH Present N=27 WMH Absent N=9 WMH Present N=9 MOCA Mean (SD) (3.54) (5.32) (6.78) (4.87) FAB Mean (SD) (1.51) (2.54) (3.27) (2.92) ADAS- 11 Mean (SD) (9.58) (8.38) 17 (12.95) (9.25) GDS Mean (SD) 1.38 (1.06) 2.29 (1.43) 1.33 (1.66) 1.89 (1.69) Table 4. Correlation between cognitive scores, stratified by ApoE4 status in WM disease Total WMH ApoE4 + (N=18) ApoE4 - (N=35) MMSE p= p=0.472 MOCA p= p=0.04 FAB p= p=0.165 ADAS p= p=0.701 GDS 0.31 p= p= DISCLOSURES / CONTACT INFORMATION REFERENCES Saunders AM, Strittmatter WJ, et al. Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer’s disease. Neurology. 1993; 43:1467–72. Roses AD. Apolipoprotein E alleles as risk factors in Alzheimer’s disease. Annu Rev Med. 1996; 47:387–400. Chuang YF, Hayden KM, Norton MC, Tschanz J, Breitner JC, Welsh-Bohmer KA, et al. Association between APOE epsilon4 allele & vascular dementia: The Cache County study. Dement Geriatr Cogn Disord. 29: Scheltens P, Erkinjunti T, Leys D, Wahlund LO, Inzitari D, del Ser T, Pasquier F, Barkhof F, Fazekas F, Pantoni L. White matter changes on CT and MRI: an overview of visual rating scales European Task Force on Age- Related White Matter Changes. Eur Neurol. 1998; 39: 80–89