Apolipoprotein E-polymorphism, frailty and mortality in older adults

Abstract

Although apolipoprotein E (ApoE) polymorphism is associated with variable risks of several illnesses, and with mortality, no persuasive relationship has been demonstrated with frailty. Here, the clinical examination cohort (n=1452 older adults, aged 70+ years at baseline) of the Canadian Study of Health and Aging was evaluated, with 5-year follow-up data. Frailty was defined using both the phenotypic definition from the Cardiovascular Health Study (Frailty-CHS) and the 'Frailty Index', from which age-specific trajectories of deficit accumulation can be estimated. In age-sex adjusted analyses, people with ApoE 4 allele had a higher risk of death (hazard ratio [HR]=1.20; 95% confidence interval: 1.01-1.45), but this relationship was not significant when adjusted for cognitive impairment (1.06; 95% confidence interval: 0.88-1.27). There was no association between frailty and ApoE polymorphism, defined in age-sex adjusted models either as Frailty-CHS (ApoE4 HR 1.17; 95% confidence interval: 0.98-1.40, frailty HR 1.37; 95% confidence interval: 1.28-1.46) or by the Frailty Index (ApoE4 HR 1.07; 95% confidence interval: 0.90-1.29, frailty HR 35.3; 95% confidence interval: 20.4-61.1). The data do not support an association between ApoE polymorphism and frailty. This result did not depend on how frailty was defined.

Fig. 1

Characteristics of the sample. Panel A: age-specific prevalence of ApoE alleles. The solid line corresponds to ε3/ε3 (n= 435), the dashed line to ApoE4 (ε2/ε4, ε3/ε4, ε4/ε4, n= 127) and the dot-dashed line to ApoE2 (ε2/ε2 and ε2/ε3, n= 89). Panel B: Relationship between the number of ApoE ε4 alleles (0,1,2) and cognitive diagnoses – No Cognitive Impairment (NCI, n= 651), Cognitive Impairment, No Dementia (CIND, n= 447) and dementia (n= 354).

Fig. 2

Survival in relation to the number of copies of the ApoE ε4 allele. In both Panels, the solid line corresponds to 0 ApoE ε4 alleles, the dashed line to 1 ApoE ε4 allele and the dotted line to 2 ApoE ε4 alleles. Panel A: adjusted for age and sex, the hazard ratios are significantly different from each other (P= 0.03). Panel B: adjusted for age, sex and cognitive impairment, the differences are no longer statistically significant (P= 0.45).

Fig. 3

The relationship between ApoE alleles and frailty, according to the Frailty-CHS definition (Panel A) and the Frailty Index (Panel B).

Fig. 4

The relationship between ApoE alleles, frailty and age, according to the Frailty-CHS definition (Panel A, for people age 70–79; Panel B, for people aged 80) and the Frailty Index (Panel B).

Fig. 5

Frailty in relation to ApoE allele and the degree of cognitive impairment. Panel A shows the sample divided by cognitive status (upper third, No Cognitive Impairment, middle third, Cognitive Impairment no Dementia (CIND), and lower third dementia) according to the Frailty-CHS groupings of robust, pre-frail and frail. Panel B shows the cumulative distributions of the Frailty Index values in relation to the degree of cognitive impairment and ApoE genotype.

Fig. 6

ApoE genotype in relation to mean frailty index values, cross-classified by the CHS frailty definition groups.