The Israel Registry for Alzheimer's Prevention (IRAP) study of middle‐aged offspring of Alzheimer’s disease patients

Abstract

AbstractBackgroundParental family history of AD is a well‐established risk factor for late onset AD (LOAD). Since AD‐related neuropathology starts decades prior to dementia onset, studying middle‐aged asymptomatic offspring of LOAD patients provides an opportunity to assess the role of genetic, health related, lifestyle and environmental factors in the very earliest stages of the disease course.MethodThe Israel Registry for Alzheimer’s Prevention (IRAP) study follows a cohort of middle‐aged offspring of AD patients (FH+; n=409) and controls (FH‐, i.e. offspring of non‐demented parents; n=104). The study collects detailed cognitive, health‐related, genetic, lifestyle and brain imaging data. Follow‐up waves will be every 3 years. All participants are members of the Israeli HMO‐ Maccabi Health Services, so detailed medical information is available on them since 1998. Here we compare baseline socio‐demographic, lifestyle, health‐related and cognitive data of FH+ vs. FH‐ participants. Comparisons between groups were done using χ2 for categorical variables, ANCOVAs for continuous variables (laboratory and lifestyle) adjusting for age, sex and education, and MANCOVAs for cognitive scores done separately for tests of episodic memory, working memory, executive functions, and language.ResultParticipants characteristics by family history status are presented in Table 1. Mean subjects' age is 54.83 (SD=6.7), 16.47 (SD=3.06) years of education; 35.7% are men; 69% of FH+ have maternal AD. Compared to FH‐, FH+ were younger (p=0.007), more often men (p=0.003) and with higher rates of the Apo E4 allele (p=0.036). Groups did not differ in other laboratory, medical and lifestyle (exercise, alcohol consumption, smoking) variables, depression scores (CES‐D) or rates of subjective memory complaints. FH+ performed worse in episodic memory (F=2.224; p=0.025) and in executive functions (F=2.850; p=0.015) but not in working memory (F=1.172; p=0.322) and language (F=1.210; p=0.303) (Table 2). Additional adjustment for APOE‐4 resulted in loss of significance for episodic memory (F=1.830; p=0.070), while executive functions remained significant (F=2.462; p=0.032).ConclusionAsymptomatic middle‐aged offspring of AD patients perform worse on tests of episodic memory and executive functions consistent with a decades‐long prodromal course of disease. APOE4 mediates the association of FH with episodic memory but not with executive functions.