Association of ß-Amyloid and apolipoprotein e e4 with memory decline in preclinical Alzheimer disease

Abstract

IMPORTANCE Older age, high levels of ß-amyloid (Aß), and the presence of the apolipoprotein E (APOE) e4 allele are risk factors for Alzheimer disease (AD). However, the extent to which increasing age, Aß, and e4 are associated with memory decline remains unclear, and the age at which memory decline begins for Aß-positive e4 carriers and noncarriers has not been determined. OBJECTIVE To determine the association of age, Aß level, and APOE e4 with memory decline in a large group of cognitively healthy older adults. DESIGN, SETTING, AND PARTICIPANTS This longitudinal observational study included cognitively healthy older adults (age >60 years) enrolled in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study from March 31, 2006, through March 31, 2017; of 1583 individuals enrolled, 1136 refused or were excluded owing to other criteria (eg, having mild cognitive impairment or AD). Participants underwent Aß imaging in research clinics in Perth and Melbourne and more than 72 months of follow-up (at 18-month intervals). The association of age with memory was fitted to a quadratic model. Age was treated as a continuous, time-dependent variable. EXPOSURES ß-Amyloid imaging using positron emission tomography, genotyping for APOE e4, and longitudinal neuropsychological assessments of episodic memory during the 72-month follow-up. MAIN OUTCOMES AND MEASURES Episodic memory composite score. RESULTS Of the 447 participants, 203 (45.4%) were men and 244 (54.6%) were women; mean (SD) age was 72.5 (6.6) years. Equal proportions of female participants were observed in each Aß-e4 group (24 of 51 Aß-positive e4 noncarriers [47.1%]; 35 of 64 Aß-negative e4 carriers [54.7%]; 40 of 72 Aß-positive e4 carriers [55.6%]; and 145 of 260 Aß-negative e4 noncarriers [55.8%]). Adults with Aß findings (mean [SD] age, 74.4 [6.8] years) were approximately 4 years older than those negative for Aß (mean [SD] age, 69.8 [6.1] years). Memory decline diverged significantly from Aß-negative e4 noncarriers at an earlier age in Aß-positive e4 carriers (64.5 years) than in Aß-positive e4 noncarriers (76.5 years), such that by 85 years of age, Aß-positive e4 carriers performed approximately 1.5 SD units worse on the episodic memory composite than Aß-negative e4 noncarriers and approximately 0.8 SD units worse than Aß-positive e4 noncarriers. Memory performance of Aß-negative e4 carriers did not differ from that of the Aß-negative e4 noncarriers (estimate [SE], 0.001 [0.001]; t = 0.526; P = .77). CONCLUSIONS AND RELEVANCE Prior work has shown that Aß and e4 combine to influence memory decline in nondemented older adults. Results of this study indicate that increasing age May further exacerbate these effects. The estimates provided May be used to determine the risk of memory decline associated with Aß and e4 at each age.