Effects of Food and Drug Administration-approved medications for Alzheimer鈥檚 disease on clinical progression

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• 作者：Michelle M. Mielke^a ; ^{mmielke1@jhmi.edu} ; Jeannie-Marie Leoutsakos^a ; Chris D. Corcoran^b ; ^c ; Robert C. Green^d ; Maria C. Norton^b ; ^e ; ^f ; Kathleen A. Welsh-Bohmer^g ; JoAnn T. Tschanz^b ; ^e ; Constantine G. Lyketsos^a
• 关键词：Cholinesterase inhibitor ; Memantine ; Incident Alzheimer&rsquo ; s disease ; Population-based ; Disease progression ; Sex ; APOE
• 刊名：Alzheimer's Dementia
• 出版年：2012
• 期刊代码：6_15525260
• 类别：med
• 出版时间：May, 2012
• 卷：8
• 期：3
• 页码：180-187
• 文件大小：206 K

摘要

Background

Observational studies suggest that cholinesterase inhibitors and/or memantine may delay clinical progression of Alzheimer鈥檚 disease (AD) in 40%of individuals taking the medications. Given this response and existence of side effects, we sought to quantify medication use and benefits in a population-based study of incident AD cases.

Methods

The Cache County Dementia Progression Study enrolled and followed a cohort of 327 incident AD cases for a maximum of 9 years. Drug exposure was expressed using a persistency index (PI), calculated as total years of drug use divided by total years of observation. Linear mixed-effects models examined PI, and interactions with sex and apolipoprotein E (m>APOEm>) as predictors of clinical progression on the Mini-Mental State Examination and Clinical Dementia Rating-Sum of Boxes.

Results

A total of 69 participants (21.1%) reported having ever used cholinesterase inhibitors or memantine. There was a strong three-way interaction between PI, sex, and time. Among women, a higher PI (i.e., greater duration of use) of cholinesterase inhibitors was associated with slower progression on the Mini-Mental State Examination and Clinical Dementia Rating-Sum of Boxes, particularly among those with an m>APOEm> 蓻4 allele. In contrast, higher PI was associated with faster progression in males.

Conclusion

A low percentage of individuals with AD in the community are taking cholinesterase inhibitors or memantine. This study suggests that women, particularly those with an m>APOEm> 蓻4 allele, may benefit the most from these medications. With the newly approved increased dose of donepezil, it will be imperative to determine whether a higher dose is needed in men or whether other factors warrant consideration.