MEASURING THE INTERACTION BETWEEN PUTATIVE PATHOLOGICAL STATUS IN ALZHEIMER'S DISEASE PATHOLOGY AND CARDIOVASCULAR RISKS IN AMNESTIC MCI INDIVIDUALS STRATIFIED BY APOE GENOTYPE

In a previous study (Bodryzlova et al.; Alz Dementia 10(4):P151) we demonstrated how 75% of MCI to AD conversion cases could be explained by the interaction between Alzheimer's disease pathology (ADP) and cardiovascular risk factors (CVR). However, there were limitations to this study, namely our using Mini-Mental State Examination (MMSE) results as a proxy of ADP, and how both exposures could have been overestimated due our using odds ratios instead of relative risk (RR). Further, we did not take apolipoprotein E genotype (APOE) status into account. The objective of the current study was to overcome these limitations by calculating the fraction of conversion cases attributable to the interaction (FAI) between ADP and CVR by APOE strata, using conversion probability as an association measure in groups exposed to ADP only (P01), CVR only (P10), both (P11) or none (P00). We used data on MCIs from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) 1 dataset (total 404 subjects). We stratified participants according to their APOE genotype into either allele 4 non-carriers, heterozygote, or homozygote carriers. The ADP proxy was chosen as the dichotomized score on either the Wechsler Logical Memory delayed recall test, the Rey Auditory Verbal Learning test, the Alzheimer’s Disease Assessment Scale test, the MMSE, or the MMSE delayed recall. The CVR proxy was a dichotomized sum of normative levels in blood arterial tension, cholesterol and triglycerides (0 – normative level, 1 – moderate increase, 2 – considerable increase) compared to cognitively healthy controls in ADNI. We calculated the FAI as P11/(P11-P10-P01+P00). We found no conversion cases attributable to the interaction between ADP and CVR in APOE4 non-carriers and heterozygote subjects. In homozygote carriers the FAI varied according to the proxy chosen: for the MMSE it reached 68% (p=0,004); the Wechsler 66% (p=0,009); the Assessment Scale 58% (p=0,02); and the Rey Auditory 62% (p=0,02). The MMSE delayed recall was not significant (47%, p=0.12). More than half of all conversion cases in the APOE e4 homozygote carriers seemed due to the interaction between ADP and CVR. Further, this was evident using a multitude of tests assessing functions other than episodic memory.