Using a community sample of 1205 elderly persons, we investigated the associations and potential interactions between Apolipoprotein E (APOE) genotype and serum phosphatidylethanolamine (PlsEtn) on cognition and dementia. For each person, APOE genotype, PlsEtn Biosynthesis value (PBV, the combination of three key PlsEtn species), cognition (the combination of five specific cognitive domains), and diagnosis of dementia was determined. APOE genotype and PBV were observed to be non-interacting (p > 0.05) and independently associated with cognition: APOE (relative to ε3ε3:ε2ε3 (Coef = 0·14, p = 4.2 × 10-2); ε3ε4/ε4ε4 (Coef = -0.22, p = 6.2 × 10-5); PBV (Coef = 0.12, p = 1.7 × 10-7) and dementia: APOE (relative to ε3ε3:ε2ε3 (Odds Ratio OR = 0.44, p = 3.0 × 10-2); ε3ε4/ε4ε4 (OR = 2.1, p = 2.2 × 10-4)); PBV (OR = 0.61, p = 3.3 × 10-6). Associations are expressed per standard deviation (SD) and adjusted for serum lipids and demographics. Due to the independent and non-interacting nature of the APOE and PBV associations, the prevalence of dementia in APOE ε3ε4/ε4ε4 persons with high PBV values (>1 SD from mean) was observed to be the same as APOE ε3ε3 persons (14.3% versus 14.0%). Similarly, the prevalence of dementia in APOE ε3ε3 persons with high PBV values was only 5.7% versus 6.7% for APOE ε2ε3 persons. The results of these analyses indicate that the net effect of APOE genotype on cognition and the prevalence of dementia is dependent upon the plasmalogen status of the person.
Keywords: APOE; Alzheimer’s disease; cholesterol; cognition; dementia; plasmalogen.