Relation of Serum Plasmalogens and APOE Genotype to Cognition and Dementia in Older Persons in a Cross-Sectional Study

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 e3e3:e2e3 (Coef = 0·14, p = 4.2 × 10−2); e3e4/e4e4 (Coef = −0.22, p = 6.2 × 10−5); PBV (Coef = 0.12, p = 1.7 × 10−7) and dementia: APOE (relative to e3e3:e2e3 (Odds Ratio OR = 0.44, p = 3.0 × 10−2); e3e4/e4e4 (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 e3e4/e4e4 persons with high PBV values (>1 SD from mean) was observed to be the same as APOE e3e3 persons (14.3% versus 14.0%). Similarly, the prevalence of dementia in APOE e3e3 persons with high PBV values was only 5.7% versus 6.7% for APOE e2e3 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.