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

Abstract

Using a community sample of 1205 elderly persons, we investigated the associations and potential interactions between Apolipoprotein E (<i>APOE)</i> genotype and serum phosphatidylethanolamine (PlsEtn) on cognition and dementia. For each person, <i>APOE</i> 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. <i>APOE</i> genotype and PBV were observed to be non-interacting (<i>p</i> > 0.05) and independently associated with cognition: <i>APOE</i> (relative to ε3ε3:ε2ε3 (Coef = 0·14, <i>p</i> = 4.2 × 10^-²); ε3ε4/ε4ε4 (Coef = -0.22, <i>p</i> = 6.2 × 10^-⁵); PBV (Coef = 0.12, <i>p</i> = 1.7 × 10^-⁷) and dementia: <i>APOE</i> (relative to ε3ε3:ε2ε3 (Odds Ratio OR = 0.44, <i>p</i> = 3.0 × 10^-²); ε3ε4/ε4ε4 (OR = 2.1, <i>p</i> = 2.2 × 10^-⁴)); PBV (OR = 0.61, <i>p</i> = 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 <i>APOE</i> and PBV associations, the prevalence of dementia in <i>APOE</i> ε3ε4/ε4ε4 persons with high PBV values (>1 SD from mean) was observed to be the same as <i>APOE</i> ε3ε3 persons (14.3% versus 14.0%). Similarly, the prevalence of dementia in <i>APOE</i> ε3ε3 persons with high PBV values was only 5.7% versus 6.7% for <i>APOE</i> ε2ε3 persons. The results of these analyses indicate that the net effect of <i>APOE</i> genotype on cognition and the prevalence of dementia is dependent upon the plasmalogen status of the person.