TY - JOUR
T1 - Effect of Apolipoprotein e ϵ4 Carrier Status on Cognitive Response to Acetylcholinesterase Inhibitors in Patients with Alzheimer's Disease
T2 - A Systematic Review and Meta-Analysis
AU - Cheng, Ying Chih
AU - Huang, Yu-Chen
AU - Liu, Hsing Cheng
PY - 2018/8/1
Y1 - 2018/8/1
N2 - Background: The apolipoprotein E ϵ4 (APOE ϵ4) genotype is the major genetic risk factor for Alzheimer's disease (AD). However, its effect on an individual's response to treatment is less well understood. Many studies have reported that the presence or absence of APOE ϵ4 may have influence on the therapeutic response for acetylcholinesterase inhibitors (AChEIs), but the results were inconsistent. This study performed a systematic review and meta-analysis to evaluate the association between response of treatment with AChEIs and the APOE ϵ4 carrier status. Methods: Clinical studies with AD patients reporting APOE ϵ4 genotype were included in the analysis. Cognitive outcome was measured by the change in Mini-Mental State Examination (MMSE), cognition subscales of the Alzheimer's Disease Assessment Scale (ADAS-cog), or Cognitive Abilities Screening Instrument (CASI). A random effects model was employed to calculate the standardized mean difference (SMD) and odds ratio (OR). Results: Of the 284 screened abstracts, 38 studies were identified, 30 of which were included for meta-analysis. Continuous data for assessing the association between APOE ϵ4 and cognitive outcomes of AChEIs were available from 18 studies. The cognitive outcomes showed no significant difference between APOE ϵ4 carriers and APOE ϵ4 non-carriers (SMD = 0.022, 95% CI: -0.089∼0.133, p = 0.702, I2 = 55.3%). Twelve studies with binary data were included, also revealing insignificant difference between the two groups (OR = 1.164, 95% CI: 0.928∼1.459, p = 0.189, I2 = 16.4%). Subgroup analysis indicated that AChEIs were significantly more effective than placebo in both groups. Conclusions: APOE ϵ4 carrier status had no significant influence on the treatment response to AChEIs in patients with AD. AChEIs had a positive therapeutic effect compared with placebo regardless of APOE ϵ4 carrier status.
AB - Background: The apolipoprotein E ϵ4 (APOE ϵ4) genotype is the major genetic risk factor for Alzheimer's disease (AD). However, its effect on an individual's response to treatment is less well understood. Many studies have reported that the presence or absence of APOE ϵ4 may have influence on the therapeutic response for acetylcholinesterase inhibitors (AChEIs), but the results were inconsistent. This study performed a systematic review and meta-analysis to evaluate the association between response of treatment with AChEIs and the APOE ϵ4 carrier status. Methods: Clinical studies with AD patients reporting APOE ϵ4 genotype were included in the analysis. Cognitive outcome was measured by the change in Mini-Mental State Examination (MMSE), cognition subscales of the Alzheimer's Disease Assessment Scale (ADAS-cog), or Cognitive Abilities Screening Instrument (CASI). A random effects model was employed to calculate the standardized mean difference (SMD) and odds ratio (OR). Results: Of the 284 screened abstracts, 38 studies were identified, 30 of which were included for meta-analysis. Continuous data for assessing the association between APOE ϵ4 and cognitive outcomes of AChEIs were available from 18 studies. The cognitive outcomes showed no significant difference between APOE ϵ4 carriers and APOE ϵ4 non-carriers (SMD = 0.022, 95% CI: -0.089∼0.133, p = 0.702, I2 = 55.3%). Twelve studies with binary data were included, also revealing insignificant difference between the two groups (OR = 1.164, 95% CI: 0.928∼1.459, p = 0.189, I2 = 16.4%). Subgroup analysis indicated that AChEIs were significantly more effective than placebo in both groups. Conclusions: APOE ϵ4 carrier status had no significant influence on the treatment response to AChEIs in patients with AD. AChEIs had a positive therapeutic effect compared with placebo regardless of APOE ϵ4 carrier status.
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U2 - 10.1159/000490175
DO - 10.1159/000490175
M3 - Article
C2 - 30041236
AN - SCOPUS:85051714712
SN - 1420-8008
VL - 45
SP - 335
EP - 352
JO - Dementia and Geriatric Cognitive Disorders
JF - Dementia and Geriatric Cognitive Disorders
IS - 5-6
ER -
