Effect of APOE and CD33 on cognitive decline

Abstract

Objective An Alzheimer's disease (AD) diagnosis is preceded by a long period of cognitive decline. We previously demonstrated increased risk of decline among individuals possessing one or more APOE ε4 alleles together with a family history of AD. The objective of this study is to investigate the possibility that such an increased risk might be due to AD risk genes with small effects in combination with APOE. Methods Participants in the Health and Retirement Study (HRS) over the age of 65, who contributed DNA, and had two or more evaluations with an abbreviated version of the modified Telephone Interview for Cognitive Status (TICS-m) were eligible for the study (n = 7451). A genetic risk score (g-score) was derived using AD risk genes' meta-analyses data, assigning risk according to the number of risk alleles and summed over all the risk genes. Trajectories of cognitive function were modeled in four groups of Caucasian participants with and without one or more APOE ε4 alleles and either a high or low g-score: APOE ε4-/low gscore; APOE ε4-/high g-score; APOE ε4+/low g-score; and APOE ε4+/high g-score. Post hoc analyses evaluated interactions between individual genes and APOE. Results Individuals in the APOE ε4+/high g-score group exhibited the greatest cognitive decline over time (p