Angiotensin Converting Enzyme Inhibitors and Alzheimer Disease in the Presence of the Apolipoprotein E4 Allele

• Published in: The American journal of geriatric psychiatry 2014-02, Vol.22 (2), p.177-185
• Main Authors: Qiu, Wendy Wei Qiao, M.D., Ph.D, Lai, Angela, Mon, Timothy, Mwamburi, Mkaya, M.D., Ph.D, Taylor, Warren, M.D, Rosenzweig, James, M.D, Kowall, Neil, M.D, Stern, Robert, Ph.D, Zhu, Haihao, M.D., Ph.D, Steffens, David C., M.D., M.H.S
• Format: Article
• Language: English
• Subjects: ACE inhibitor; Aged; Alleles; Alzheimer disease; Alzheimer Disease - blood; Alzheimer Disease - drug therapy; Alzheimer Disease - genetics; Alzheimer Disease - psychology; angiotensin converting enzyme (ACE); Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Apolipoprotein E4 - genetics; Apolipoprotein E4 allele (ApoE4); Cross-Sectional Studies; Female; Humans; Internal Medicine; Male; Neuropsychological Tests; Peptidyl-Dipeptidase A - blood
• ISSN: 1064-7481; 1545-7214
• DOI: 10.1016/j.jagp.2012.08.017

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.