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Cochrane Database of Systematic Reviews

Vitamin E for Alzheimer's dementia and mild cognitive impairment

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DOI:
https://doi.org/10.1002/14651858.CD002854.pub4Copy DOI
Database:
  1. Cochrane Database of Systematic Reviews
Version published:
  1. 27 January 2017see what's new
Type:
  1. Intervention
Stage:
  1. Review
Cochrane Editorial Group:
  1. Cochrane Dementia and Cognitive Improvement Group

Copyright:
  1. Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Authors

  • Nicolas Farina

    Correspondence to: Centre for Dementia Studies, Brighton and Sussex Medical School, Brighton, UK

    [email protected]

  • David Llewellyn

    Medical School, University of Exeter, Exeter, UK

  • Mokhtar Gad El Kareem Nasr Isaac

    Old Age Psychiatry, Sussex Partnership NHS Foundation Trust, Eastbourne, UK

  • Naji Tabet

    Centre for Dementia Studies, Brighton and Sussex Medical School, Brighton, UK

Contributions of authors

Original: NT drew up the protocol. M Isaac (MI) planned the review and protocol, selected studies, critiqued the trials, advised on analyses, revised drafts of protocol and review and supervised the review process.

Update 2006: MI and Rebecca Quinn (RQ) reviewed and selected the included studies. MI extracted the data, performed the analysis and wrote the draft. NT contributed to the text and supervised. The search was carried out by Dymphna Hermans.

Update 2012: NF and MI reviewed and selected the included studies. NF extracted the data and wrote the draft. Annalie R Clark (AC), Jennifer Rusted (JR) and NT contributed to the text. JR and NT supervised. The search was carried out by Anna‐Noel Storr.

Update 2016: NF and DL independently reviewed and extracted descriptive data from included studies. NF, NT and DL independently extracted outcome data. NF wrote the initial draft. DL, MI and NF all contributed to the text. NT made the final decision on any disagreements between authors. The search was carried out by Anna‐Noel Storr.

Sources of support

Internal sources

  • Centre for Dementia Studies, Brighton & Sussex Medical School, UK.

External sources

  • NIHR, UK.

    This update was supported by the National Institute for Health Research (NIHR), via Cochrane Infrastructure funding to the Cochrane Dementia and Cognitive Improvement group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, National Health Service or the Department of Health

Declarations of interest

Nicolas Farina ‐ None known
David Llewellyn ‐ None known
Mokhtar Gad El Kareem Nasr Isaac‐ None known
Naji Tabet ‐ None known

Acknowledgements

The review authors are grateful to Sue Marcus, Managing Editor, Cochrane Dementia and Cognitive Improvement Group, for her support throughout the review.

The review authors would also like to thank Dr Jenny McCleery, Assistant Co‐ordinating Editor, Cochrane Dementia and Cognitive Improvement Group, for her comments and contributions in the amendment process of the review (June 2012 and April 2016).

Version history

Published

Title

Stage

Authors

Version

2017 Apr 18

Vitamin E for Alzheimer's dementia and mild cognitive impairment

Review

Nicolas Farina, David Llewellyn, Mokhtar Gad El Kareem Nasr Isaac, Naji Tabet

https://doi.org/10.1002/14651858.CD002854.pub5

2017 Jan 27

Vitamin E for Alzheimer's dementia and mild cognitive impairment

Review

Nicolas Farina, David Llewellyn, Mokhtar Gad El Kareem Nasr Isaac, Naji Tabet

https://doi.org/10.1002/14651858.CD002854.pub4

2012 Nov 14

Vitamin E for Alzheimer's dementia and mild cognitive impairment

Review

Nicolas Farina, Mokhtar Gad El Kareem Nasr Isaac, Annalie R Clark, Jennifer Rusted, Naji Tabet

https://doi.org/10.1002/14651858.CD002854.pub3

2008 Jul 16

Vitamin E for Alzheimer's disease and mild cognitive impairment

Review

Mokhtar Gad El Kareem Nasr Isaac, Rebecca Quinn, Naji Tabet

https://doi.org/10.1002/14651858.CD002854.pub2

2000 Oct 23

Vitamin E for Alzheimer's disease and mild cognitive impairment

Review

Mokhtar Gad El Kareem Nasr Isaac, Rebecca Quinn, Naji Tabet

https://doi.org/10.1002/14651858.CD002854

Differences between protocol and review

We included 'Summary of findings' tables and GRADE evaluation.

The methods of the review were updated to comply with the most recent version of the Cochrane Handbook for Systematic Reviews of Interventions (Version 5.1; Higgins 2011).

Since the June 2012 update, one new author DL has been added. AC and JR have been removed as authors.

Keywords

MeSH

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Study flow diagram for study for the search April 2016.
Figures and Tables -
Figure 1

Study flow diagram for study for the search April 2016.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figures and Tables -
Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figures and Tables -
Figure 3

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 1 Alzheimer's Disease Assessment Scale ‐ Cognitive subscale (ADAS‐Cog) (least square (LS) mean change from baseline at 6 to 48 months): completers.
Figures and Tables -
Analysis 1.1

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 1 Alzheimer's Disease Assessment Scale ‐ Cognitive subscale (ADAS‐Cog) (least square (LS) mean change from baseline at 6 to 48 months): completers.

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 2 Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS‐ADL) (LS mean change from baseline at 6 to 48 months): completers.
Figures and Tables -
Analysis 1.2

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 2 Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS‐ADL) (LS mean change from baseline at 6 to 48 months): completers.

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 3 Deaths (number of deaths over 48 months).
Figures and Tables -
Analysis 1.3

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 3 Deaths (number of deaths over 48 months).

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 4 Serious adverse events (number of participants reporting ≥ 1 serious adverse event over 48 months).
Figures and Tables -
Analysis 1.4

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 4 Serious adverse events (number of participants reporting ≥ 1 serious adverse event over 48 months).

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 5 Neuropsychiatric Inventory (NPI) (LS mean change from baseline at 6 to 48 months): completers.
Figures and Tables -
Analysis 1.5

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 5 Neuropsychiatric Inventory (NPI) (LS mean change from baseline at 6 to 48 months): completers.

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 6 Mini‐Mental State Examination (MMSE) (LS mean change from baseline at 6 to 48 months): completers.
Figures and Tables -
Analysis 1.6

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 6 Mini‐Mental State Examination (MMSE) (LS mean change from baseline at 6 to 48 months): completers.

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 7 Adverse events (number of participants reporting ≥ 1 adverse event over 48 months).
Figures and Tables -
Analysis 1.7

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 7 Adverse events (number of participants reporting ≥ 1 adverse event over 48 months).

Comparison 2 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with mild cognitive impairment, Outcome 1 Progression to Alzheimer's disease (AD) (number of people progressing to AD by 36 months).
Figures and Tables -
Analysis 2.1

Comparison 2 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with mild cognitive impairment, Outcome 1 Progression to Alzheimer's disease (AD) (number of people progressing to AD by 36 months).

Comparison 2 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with mild cognitive impairment, Outcome 2 Deaths (number of deaths over 36 months).
Figures and Tables -
Analysis 2.2

Comparison 2 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with mild cognitive impairment, Outcome 2 Deaths (number of deaths over 36 months).

Summary of findings for the main comparison. Vitamin E (capsules 2000 IU/day in two divided doses) compared to placebo for people with Alzheimer's disease

Vitamin E (capsules 2000 IU/day in 2 divided doses) compared to placebo for people with Alzheimer's disease

Patient or population: people with Alzheimer's disease

Settings: multicentre, US

Intervention: vitamin E (capsules 2000 IU/day in 2 divided doses)

Comparison: placebo

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Placebo

Vitamin E (capsules 2000 IU/day in 2 divided doses)

Cognitive function
LS mean change from baseline using the ADAS‐Cog

Scale from: 0 to 70

Follow‐up: 6 to 48 months

The LS mean change from baseline in cognitive function in placebo group was 7.78

The LS mean change from baseline in cognitive function in the intervention group was 1.81 lower
(3.75 lower to 0.13 higher)

272
(1 study)

⊕⊕⊕⊝
Moderate1

Higher scores represent worse cognitive function.

A 4‐point difference in ADAS‐cog has been considered the MCID.

Adverse events

Number of participants reporting ≥ 1 serious adverse event

Follow‐up: 6 to 48 months

625 per 1000

538 per 1000
(444 to 656)

RR 0.86
(0.71 to 1.05)

304
(1 study)

⊕⊕⊕⊝
Moderate1

Deaths

Number of deaths

Follow‐up: 6 to 48 months

204 per 1000

171 per 1000
(106 to 273)

RR 0.84
(0.52 to 1.34)

304
(1 study)

⊕⊕⊕⊝
Moderate1

Activities of daily living
LS mean change from baseline using the ADCS‐ADL

Scale from: 0 to 78

Follow‐up: 6 to 48 months

The LS mean change from baseline in activities of daily living in the placebo group was ‐16.96

The LS mean change from baseline in activities of daily living in the intervention group was 3.15 higher
(0.07 to 6.23 higher)

280
(1 study)

⊕⊕⊕⊝
Moderate1

Higher scores represent better activities of daily living.

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

ADAS‐Cog: Alzheimer Disease Assessment Scale ‐ Cognitive Subscale; ADCS‐ADL: Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory;CI: confidence interval; LS: least square; MCID: minimum clinically important difference; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1Quality downgraded one level due to imprecision. Evidence from a single study of modest size. This is supported by dichotomous data not reaching the optimal information size criterion (assuming α of 0.05, and β of 0.2) (Guyatt 2011).

Figures and Tables -
Summary of findings for the main comparison. Vitamin E (capsules 2000 IU/day in two divided doses) compared to placebo for people with Alzheimer's disease
Summary of findings 2. Vitamin E (capsules 2000 IU/day in two divided doses) compared to placebo for people with mild cognitive impairment

Vitamin E (capsules 2000 IU/day in 2 divided doses) compared to placebo for people with mild cognitive impairment

Patient or population: people with mild cognitive impairment
Settings: US and Canada
Intervention: vitamin E (capsules 2000 IU/day in 2 divided doses)
Comparison: placeb

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Placebo

Vitamin E (capsules 2000 IU/day in 2 divided doses)

Progression to Alzheimer's disease

Number of people progressing to AD

Follow‐up: 36 months

284 per 1000

293 per 1000
(224 to 383)

RR 1.03
(0.79 to 1.35)

516
(1 study)

⊕⊕⊕⊝
Moderate1

Cognitive function

Mean change from baseline of ADAS‐Cog

Scale from: 0 to 70

Follow‐up: 36 months

Not possible to extract data for analysis.

Not possible to extract data for analysis.

Unable to evaluate quality of evidence.

Uncertainty about how missing data were handled. Study reports no significant difference between intervention and control groups.

Adverse events

Number of participants reporting ≥ 1 serious adverse event.

Follow‐up: 36 months

Not possible to extract data for analysis.

516
(1 study)

Unable to evaluate quality of evidence.

Overall adverse event rates not reported.

Death

Number of deaths over 36 months

Follow‐up: 36 months

19 per 1000

19 per 1000
(6 to 66)

RR 1.01
(0.3 to 3.44)

516
(1 study)

⊕⊕⊕⊝
Moderate1

Activities of daily living

Mean change from baseline using the ADCS
Mild Cognitive Impairment Activities of Daily Living

Scale from: 0 to 53

Follow‐up: 36 months

Not possible to extract data for analysis.

Not possible to extract data for analysis.

Unable to evaluate quality of evidence.

Uncertainty about how missing data were handled. Study reports no significant difference between intervention and control groups.

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

ADAS‐Cog: Alzheimer Disease Assessment Scale ‐ Cognitive Subscale; ADCS‐ADL: Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory;CI: confidence interval; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1Quality downgraded one level due to imprecision. Evidence from a single study of modest size. This was supported by dichotomous data not reaching the optimal information size criterion (assuming α of 0.05, and β of 0.2) (Guyatt 2011).

Figures and Tables -
Summary of findings 2. Vitamin E (capsules 2000 IU/day in two divided doses) compared to placebo for people with mild cognitive impairment
Comparison 1. Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Alzheimer's Disease Assessment Scale ‐ Cognitive subscale (ADAS‐Cog) (least square (LS) mean change from baseline at 6 to 48 months): completers Show forest plot

1

272

Mean Difference (IV, Random, 95% CI)

‐1.81 [‐3.75, 0.13]

2 Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS‐ADL) (LS mean change from baseline at 6 to 48 months): completers Show forest plot

1

280

Mean Difference (IV, Fixed, 95% CI)

3.15 [0.07, 6.23]

3 Deaths (number of deaths over 48 months) Show forest plot

1

304

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.52, 1.34]

4 Serious adverse events (number of participants reporting ≥ 1 serious adverse event over 48 months) Show forest plot

1

304

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.71, 1.05]

5 Neuropsychiatric Inventory (NPI) (LS mean change from baseline at 6 to 48 months): completers Show forest plot

1

280

Mean Difference (IV, Fixed, 95% CI)

‐1.47 [‐4.26, 1.32]

6 Mini‐Mental State Examination (MMSE) (LS mean change from baseline at 6 to 48 months): completers Show forest plot

1

273

Mean Difference (IV, Fixed, 95% CI)

0.19 [‐0.72, 1.10]

7 Adverse events (number of participants reporting ≥ 1 adverse event over 48 months) Show forest plot

1

304

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.85, 1.23]

Figures and Tables -
Comparison 1. Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease
Comparison 2. Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with mild cognitive impairment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Progression to Alzheimer's disease (AD) (number of people progressing to AD by 36 months) Show forest plot

1

516

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.79, 1.35]

2 Deaths (number of deaths over 36 months) Show forest plot

1

516

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.30, 3.44]

Figures and Tables -
Comparison 2. Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with mild cognitive impairment