P2–315: Effects of Biomarkers on Cognitive Domains in Alzheimer's Disease

Efforts to better understand Alzheimer's Disease (AD) have included epidemiologic studies and clinical trials, some of which have used different biomarkers. These different biomarkers could be used to elucidate the causal pathways that contribute to cognitive domains in AD. This study investigates the association of cognitive domains of the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and the Mini-Mental State Examination (MMSE) with biomarkers of AD pathophysiology (specifically the presence of the Apolipoprotein E (APOE)). Data was obtained from the Critical Path Institute Online Data Repository (CODR). We studied 1,158 patients with AD (507 APOE non-carriers, 146 Homozygous, 505 APOE carriers). Cognition variables included change in scores from Week 1 to Week 4 on each item of the ADAS-Cog, ADAS-Cog Total Score and the MMSE total score. We applied 2 independent methods-partial correlation analysis adjusted for age and gender and path analysis to evaluate the associations between biomarkers and cognition. Comparative Fit Index (CFI) and Normed Fit Index (NFI fit) were examined, values close to 1 are considered to indicate a good fit. No significant correlations were observed for the ADAS-Cog items, ADAS-Cog total score or MMSE total score with the APOE biomarker, and the path associations between ADAS-Cog Total scores and MMSE total scores with biomarkers were not significant (p > 0.05). The model that provided the best fit (NFI (0.80) and CFI (0.81)) included change from Week 1 to Week 4 in items of comprehension, word finding, remembering instructions, word recall, as non-significant predictors of and APOE group. The change in comprehension score was 0.52 points higher for APOE carriers than for non-carriers, however results were not significant, and 18% of the variance in the comprehension score was explained by remembering instructions score. Despite studies showing response to treatment and longitudinal cognitive outcome as better in non-carriers of the APOE allele, our results did not show any significant differences in change in APOE group and changes in individual items on the ADAS-Cog, total ADAS-Cog score or MMSE total score. These observations should be replicated and further examination of the contribution of the ADAS-Cog to the assessment of AD.