Wendy Wei Qiao Qiu1, Angela Lai2, Timothy Mon2, Mkaya Mwamburi3, Warren Taylor4, James Rosenzweig5, Neil Kowall6, Robert Stern6, Haihao Zhu2, David C Steffens7. 1. Department of Pharmacology & Experimental Therapeutics, Boston University School of Medicine, Boston, MA; Department of Psychiatry, Boston University School of Medicine, Boston, MA; Department of Alzheimer Disease Center, Boston University School of Medicine, Boston, MA. Electronic address: wqiu67@bu.edu. 2. Department of Pharmacology & Experimental Therapeutics, Boston University School of Medicine, Boston, MA. 3. Department of Public Health and Community Medicine, Tufts University, Boston, MA. 4. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC. 5. Department of Medicine, Boston University School of Medicine, Boston, MA. 6. Department of Alzheimer Disease Center, Boston University School of Medicine, Boston, MA. 7. Department of Psychiatry, University of Connecticut Health Center, Farmington, CT.
Abstract
OBJECTIVE: The effect of angiotensin converting enzyme (ACE) inhibitors on Alzheimer disease (AD) remains unclear, with conflicting results reported. We studied the interaction of the Apolipoprotein E (ApoE) genotype and ACE inhibitors on AD. METHODS: This was a cross-sectional study of homebound elderly with an AD diagnosis and documentation of medications taken. ApoE genotype was determined. RESULTS: A total of 355 subjects with status on ApoE alleles and cognitive diagnoses were studied. The average age (mean ± SD) of this population was 73.3 ± 8.3 years old, and 73% were female. Cross-sectionally, there was no difference in the number of AD cases between ApoE4 carriers and ApoE4 non-carriers or between ACE inhibitor users and non-users in the homebound elderly. ApoE4 carriers treated with ACE inhibitors, however, had more diagnoses of AD compared with those who did not have the treatment (28% versus 6%, p = 0.01) or ApoE4 non-carriers treated with an ACE inhibitor (28% versus 10%, p = 0.03). ACE inhibitor use was associated with AD diagnosis only in the presence of an E4 allele. Using multivariate logistic regression analysis, we found that in diagnosed AD cases there was a significant interaction between ApoE4 and ACE inhibitor use (odds ratio: 20.85; 95% confidence interval: 3.08-140.95; p = 0.002) after adjusting for age, sex, ethnicity, and education. CONCLUSION: The effects of ACE inhibitors on AD may be different depending on ApoE genotype. A prospective study is needed to determine whether ACE inhibitor use accelerates or poorly delays AD development in ApoE4 carriers compared with ApoE4 non-carriers.
OBJECTIVE: The effect of angiotensin converting enzyme (ACE) inhibitors on Alzheimer disease (AD) remains unclear, with conflicting results reported. We studied the interaction of the Apolipoprotein E (ApoE) genotype and ACEinhibitors on AD. METHODS: This was a cross-sectional study of homebound elderly with an AD diagnosis and documentation of medications taken. ApoE genotype was determined. RESULTS: A total of 355 subjects with status on ApoE alleles and cognitive diagnoses were studied. The average age (mean ± SD) of this population was 73.3 ± 8.3 years old, and 73% were female. Cross-sectionally, there was no difference in the number of AD cases between ApoE4 carriers and ApoE4 non-carriers or between ACEinhibitor users and non-users in the homebound elderly. ApoE4 carriers treated with ACEinhibitors, however, had more diagnoses of AD compared with those who did not have the treatment (28% versus 6%, p = 0.01) or ApoE4 non-carriers treated with an ACEinhibitor (28% versus 10%, p = 0.03). ACEinhibitor use was associated with AD diagnosis only in the presence of an E4 allele. Using multivariate logistic regression analysis, we found that in diagnosed AD cases there was a significant interaction between ApoE4 and ACEinhibitor use (odds ratio: 20.85; 95% confidence interval: 3.08-140.95; p = 0.002) after adjusting for age, sex, ethnicity, and education. CONCLUSION: The effects of ACEinhibitors on AD may be different depending on ApoE genotype. A prospective study is needed to determine whether ACEinhibitor use accelerates or poorly delays AD development in ApoE4 carriers compared with ApoE4 non-carriers.
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