APOE-ε4 is not associated with pure-tone hearing thresholds, visual acuity or cognition, cross-sectionally or over 3 years of follow up in the Canadian Longitudinal Study on Aging
Authors: Mick Paul , Kabir Rasel , Karunatilake Malshi , Phillips Natalie , Pichora-Fuller M. Kathleen , Young Terry-Lyn , Sosero Yuri , Gan-or Ziv , Wittich Walter 
Published: June 2023

AbstractBackgroundHearing loss and vision loss are independently and jointly associated with faster rates of cognitive decline. Identifying mechanisms underlying sensory-cognitive associations is a research priority and is needed to inform public health efforts to reduce cognitive decline. Sensory impairment is highly prevalent and treatable, and if a cause-and-effect relationship exists with cognitive decline, treating sensory impairments could reduce rates of cognitive decline with age. On the other hand, if sensory-cognitive associations are the result of a common cause (e.g., a genetic predisposition for both sensory and cognitive impairment), then interventions aimed at reducing sensory loss would not be expected to have beneficial effects on cognition.The apolipoprotein E (APOE)-ε4 allele variant is associated with age-related neurological diseases (e.g., Alzheimer’s disease) and non-neurological diseases (e.g., atherosclerosis).APOE-ε4 could be a common factor underlying associations between sensorineural losses and cognitive decline, but links betweenAPOE-ε4 and both hearing and vision in the general population remain under-studied. Furthermore, the association betweenAPOE-ε4 and cognition in healthy individuals is not as clear as the link betweenAPOE-ε4 and Alzheimer’s disease.Therefore, we aimed to determine ifAPOE-ε4 allele count (the explanatory variable) was associated with differences in baseline and 3-year change in executive function, memory, pure-tone hearing thresholds, and visual acuity (the outcome variables).MethodsA secondary analysis of data collected in the Canadian Longitudinal Study on Aging (CLSA) was performed using data from two time points 3 years apart. Participants, aged 45-85 years, were recruited from 11 cities across Canada. Composite scores for executive function and memory were developed from five tests of cognition. Bilateral air-conduction pure-tone threshold averages and pinhole-corrected visual acuity in the better-seeing eye were used to measure hearing and vision, respectively. Linear mixed regression models assessed associations betweenAPOE-ε4 allele count (as a categorical variable with 0 as the reference) and a.) baseline differences and b.) 3-year declines in each of the four outcome variables. Multivariable models adjusted for age, education, sex, race, heart disease, stroke, hypertension and diabetes. Interactions betweenAPOE-ε4 and age group (45-54, 55-64, 65-74, and 75-85 years) andAPOE-ε4 sex were tested.ResultsThere were 27,765 participants in the CLSA comprehensive cohort but only 11,296 had complete data and were included. Individuals with complete data were more likely to be younger and healthier than those with partially missing data. In main effects models,APOE-ε4 was not associated with any of the sensory or cognitive outcome measures, either in terms of differences in baseline values or change over time. Regression models including theAPOE-ε4*age interaction term (but not theAPOE-ε4*sex interaction term) better fit the data than the corresponding main effects models. In age-stratified analyses most associations betweenAPOE-ε4 and the outcome variables were still not significant. The exceptions were as follows: Twoε4 alleles predictedbetterbaseline executive function in the 55-64 year old age group, andbetterbaseline pure-tone average in the 45-54 year old age group. In the 65-74 year-old age group, one ε4 allele predicted worsening in visual acuity over time, whereas two ε4 alleles predicted improvements.DiscussionAPOE-ε4 allele count was not associated with poorer executive function, memory, pure-tone hearing thresholds or visual acuity, at baseline or over 3 years of follow-up, among a population-based sample of healthy 45-85 year old Canadians. Thus, the study does not support the hypothesis thatAPOE-ε4 is a common cause underlying associations between hearing or vision loss (respectively) and declines in each of executive function and memory.