Effect of Apolipoprotein e ϵ4 Carrier Status on Cognitive Response to Acetylcholinesterase Inhibitors in Patients with Alzheimer's Disease: A Systematic Review and Meta-Analysis

Ying Chih Cheng, Yu-Chen Huang, Hsing Cheng Liu

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)335-352
Number of pages18
JournalDementia and Geriatric Cognitive Disorders
Volume45
Issue number5-6
DOIs
Publication statusPublished - Aug 1 2018

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Apolipoprotein E4
Apolipoproteins
Cholinesterase Inhibitors
Meta-Analysis
Alzheimer Disease
Odds Ratio
Genotype
Placebos
Aptitude
Therapeutic Uses
Therapeutics
Cognition

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Cognitive Neuroscience
  • Psychiatry and Mental health

Cite this

@article{31c7c4698d374047b83d65c0e3b51cd2,
title = "Effect of Apolipoprotein e ϵ4 Carrier Status on Cognitive Response to Acetylcholinesterase Inhibitors in Patients with Alzheimer's Disease: A Systematic Review and Meta-Analysis",
abstract = "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.",
author = "Cheng, {Ying Chih} and Yu-Chen Huang and Liu, {Hsing Cheng}",
year = "2018",
month = "8",
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doi = "10.1159/000490175",
language = "English",
volume = "45",
pages = "335--352",
journal = "Dementia and Geriatric Cognitive Disorders",
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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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