Abstract
ObjectiveTo examine the interaction between APOE genotypes and both treated and untreated hypertension on cognitive function in an updated analysis of Nurses’ Health Study (NHS) data.DesignAt baseline (1995–2001) and 3 biennial follow-up assessments over ~6 years, cognitive function was assessed.Setting and participants8300 NHS participants aged 70+ years underwent a cognitive battery, which comprised 6 tests including the Telephone Interview for Cognitive Status (TICS) and tests of verbal memory, category fluency, and working memory.MeasuresWe estimated the mean differences in average cognitive scores across up to 4 assessments using multiple linear regression. We also tested for interaction between APOE e4 allele carrier status and hypertension overall, as well as for apparently untreated and treated hypertension.ResultsWe confirmed that, compared with those with APOE e3/3 genotype, APOE e4 allele carriers scored lower by 0.55 units on the average TICS score (95%CI:-0.67,-0.43). We also observed a significantly worse average TICS score among women with untreated hypertension compared with women without hypertension (difference = -0.23, 95%CI:-0.37,-0.09), while no significant difference was observed for women with treated hypertension. Significant interaction was detected between the APOE e4 allele and untreated hypertension (p-int = 0.02 for the TICS; p-int = 0.045 for global score), but not with treated hypertension. Specifically, compared with normotensive women with the APOE e3/3 genotype, APOE e4 allele carriers with treated hypertension scored lower by 0.50 units (95%CI:-0.69,-0.31); however, the APOE e4 allele carriers with untreated hypertension scored lower by 1.02 units on the TICS score (95%CI:-1.29, -0.76). This interaction of APOE e4 and untreated hypertension was also consistently observed for the global score.ConclusionsWomen with hypertension and at least one APOE e4 allele had worse average cognitive function compared with women without hypertension with the e3/3 genotype; this difference was amplified among APOE e4 allele carriers with untreated hypertension.
Highlights
The apolipoprotein E (APOE) e4 allele is a well-established genetic risk factor for cognitive impairment and late-onset Alzheimer’s disease (AD) [1,2,3,4,5]
Women with hypertension and at least one APOE e4 allele had worse average cognitive function compared with women without hypertension with the e3/3 genotype; this difference was amplified among APOE e4 allele carriers with untreated hypertension
Compared with the referent group without hypertension and e3/e3 carriers, women with untreated hypertension who had at least one APOE e4 allele scored 1.02 units lower on the Telephone Interview for Cognitive Status (TICS), which is cognitively equivalent to the effect of aging by 5.1 years (-0.20 units per 1 year of aging, 95% CI: -0.22, -0.18; p
Summary
The apolipoprotein E (APOE) e4 allele is a well-established genetic risk factor for cognitive impairment and late-onset Alzheimer’s disease (AD) [1,2,3,4,5]. Genetic testing for APOE e4 is currently not recommended, largely because of the perception that there are no interventions that reduce risk [6]. Vascular risk factors, such as hypertension, have been associated with poor cognitive function [7] and an increased risk of dementia [8]. Studies of the interaction between genetic factors (APOE e4) and hypertension on cognitive function have been conducted [9,10,11,12,13,14,15,16,17,18,19]. Few studies have examined whether antihypertensive medication use influences the association between hypertension and APOE e4 genotype on late-life cognitive function [9,12,14]
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