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. 2013;37(2):421-8.
doi: 10.3233/JAD-130716.

Angiotensin converting enzyme inhibitors and the reduced risk of Alzheimer's disease in the absence of apolipoprotein E4 allele

Wei Qiao Qiu  1 , Mkaya Mwamburi, Lilah M Besser, Haihao Zhu, Huajie Li, Max Wallack, Leslie Phillips, Liyan Qiao, Andrew E Budson, Robert Stern, Neil Kowall
Affiliations

Angiotensin converting enzyme inhibitors and the reduced risk of Alzheimer's disease in the absence of apolipoprotein E4 allele

Wei Qiao Qiu et al. J Alzheimers Dis. 2013.

Abstract

Our cross-sectional study showed that the interaction between apolipoprotein E4 (ApoE4) and angiotensin converting enzyme (ACE) inhibitors was associated with Alzheimer's disease (AD). The aim of this longitudinal study was to differentiate whether ACE inhibitors accelerate or reduce the risk of AD in the context of ApoE alleles. Using the longitudinal data from the National Alzheimer's Coordinating Center (NACC) with ApoE genotyping and documentation of ACE inhibitors use, we found that in the absence of ApoE4, subjects who had been taking central ACE inhibitor use (χ2 test: 21% versus 27%, p = 0.0002) or peripheral ACE inhibitor use (χ2 test: 13% versus 27%, p < 0.0001) had lower incidence of AD compared with those who had not been taking an ACE inhibitor. In contrast, in the presence of ApoE4, there was no such association between ACE inhibitor use and the risk of AD. After adjusting for the confounders, central ACE inhibitor use (OR = 0.68, 95% CI = 0.55, 0.83, p = 0.0002) or peripheral ACE inhibitor use (OR = 0.33, 95% CI = 0.33, 0.68, p < 0.0001) still remained inversely associated with a risk of developing AD in ApoE4 non-carriers. In conclusion, ACE inhibitors, especially peripherally acting ones, were associated with a reduced risk of AD in the absence of ApoE4, but had no such effect in those carrying the ApoE4 allele. A double-blind clinical trial should be considered to determine the effect of ACE inhibitors on prevention of AD in the context of ApoE genotype.

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Figures

Fig. 1
Fig. 1
The onset of Alzheimer’s disease among those with and without the ACE treatment in the absence and presence of ApoE4 allele. The percentages of AD onset (combined probable AD and possible AD) were compared between different subgroups: in the absence of ApoE4 (ApoE4−) or presence of ApoE4 (ApoE4+) and further divided into no ACE inhibitor use, central ACE inhibitor use, and peripheral ACE inhibitor use. Chi square (χ2 test) was used to compare between the subgroup without ACE use and either ACE inhibitor subgroup. p values for the statistical significance between the two subgroups are shown.
Fig. 2
Fig. 2
Effects of central versus peripheral ACE inhibitor use and the development of Alzheimer’s disease in ApoE4 non-carriers and ApoE4 carriers. The subjects were divided into those ApoE4 non-carriers and ApoE4 carriers. Using multivariate logistic regression models, we examined the associations between the central ACE inhibitor (central ACEI) versus peripheral ACE inhibitor (peripheral ACEI) and the development of AD after adjusting for the confounders in ApoE4 non-carriers or ApoE4 carriers separately. We used each interval between annual visits as our analysis unit taking into account non-independence of study data due to repeated measures. The confounders included age, gender, ethnicity, education, smoking, drinking, follow-up time, diabetes, hypertension, stroke, heart failure, amnestic MCI, and non-amnestic MCI. Odds ratios (95% CI) and p values are shown.
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