CoChat
Sign Up
Cited by 124Dementia and Cognitive Impairment ResearchCognitive Abilities and TestingPharmaceutical Practices and Patient Outcomes

Multi-domain interventions for the prevention of dementia and cognitive decline

Open access
Hafdi, Melanie, Hoevenaar-Blom, Marieke P., Richard, Edo·2021·Cochrane Database of Systematic Reviews
DOI 10.1002/14651858.cd013572.pub2
Open this paper in CoChat — free account

Abstract

BACKGROUND: Dementia is a worldwide concern. Its global prevalence is increasing. Currently, no effective medical treatment exists to cure or to delay the onset of cognitive decline or dementia. Up to 40% of dementia is attributable to potentially modifiable risk factors, which has led to the notion that targeting these risk factors might reduce the incidence of cognitive decline and dementia. Since sporadic dementia is a multifactorial condition, thought to derive from multiple causes and risk factors, multi-domain interventions may be more effective for the prevention of dementia than those targeting single risk factors. OBJECTIVES: To assess the effects of multi-domain interventions for the prevention of cognitive decline and dementia in older adults, including both unselected populations and populations at increased risk of cognitive decline and dementia. SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), CINAHL (EBSCOhost), Web of Science Core Collection (ISI Web of Science), LILACS (BIREME), and ClinicalTrials.gov on 28 April 2021. We also reviewed citations of reference lists of included studies, landmark papers, and review papers to identify additional studies and assessed their suitability for inclusion in the review. SELECTION CRITERIA: We defined a multi-domain intervention as an intervention with more than one component, pharmacological or non-pharmacological, but not consisting only of two or more drugs with the same therapeutic target. We included randomised controlled trials (RCTs) evaluating the effect of such an intervention on cognitive functioning and/or incident dementia. We accepted as control conditions any sham intervention or usual care, but not single-domain interventions intended to reduce dementia risk. We required studies to have a minimum of 400 participants and an intervention and follow-up duration of at least 12 months. DATA COLLECTION AND ANALYSIS: We initially screened search results using a 'crowdsourcing' method in which members of Cochrane's citizen science platform identify RCTs. We screened the identified citations against inclusion criteria by two review authors working independently. At least two review authors also independently extracted data, assessed the risk of bias and applied the GRADE approach to assess the certainty of evidence. We defined high-certainty reviews as trials with a low risk of bias across all domains other than blinding of participants and personnel involved in administering the intervention (because lifestyle interventions are difficult to blind). Critical outcomes were incident dementia, incident mild cognitive impairment (MCI), cognitive decline measured with any validated measure, and mortality. Important outcomes included adverse events (e.g. cardiovascular events), quality of life, and activities of daily living (ADL). Where appropriate, we synthesised data in random-effects meta-analyses. We expressed treatment effects as risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). MAIN RESULTS: We included nine RCTs (18.452 participants) in this review. Two studies reported incident dementia as an outcome; all nine studies reported a measure for cognitive functioning. Assessment of cognitive functioning was very heterogeneous across studies, ranging from complete neuropsychological assessments to short screening tests such as the mini-mental state examination (MMSE). The duration of the interventions varied from 12 months to 10 years. We compared multi-domain interventions against usual care or a sham intervention. Positive MDs and RRs <1 favour multi-domain interventions over control interventions. For incident dementia, there was no evidence of a difference between the multi-domain intervention group and the control group (RR 0.94, 95% CI 0.76 to 1.18; 2 studies; 7256 participants; high-certainty evidence). There was a small difference in composite Z-score for cognitive function measured with a neuropsychological test battery (NTB) (MD 0.03, 95% CI 0.01 to 0.06; 3 studies; 4617 participants; high-certainty evidence) and with the Montreal Cognitive Assessment (MoCA) scale (MD 0.76 point, 95% CI 0.05 to 1.46; 2 studies; 1554 participants), but the certainty of evidence for the MoCA was very low (due to serious risk of bias, inconsistency and indirectness) and there was no evidence of an effect on the MMSE (MD 0.02 point, 95% CI -0.06 to 0.09; 6 studies; 8697participants; moderate-certainty evidence). There was no evidence of an effect on mortality (RR 0.93, 95% CI 0.84 to 1.04; 4 studies; 11,487 participants; high-certainty evidence). There was high-certainty evidence for an interaction of the multi-domain i

AI snapshot

Written from the paper’s full text.

TL;DR

This Cochrane review assessed whether multi-domain interventions prevent cognitive decline and dementia in older adults, pooling nine RCTs (18,452 participants). It found no evidence of an effect on incident dementia, but a small improvement in cognitive function measured by a neuropsychological test battery, with the strongest effects in trials that included cognitive training.

Key findings

  • No evidence of a difference in incident dementia between multi-domain intervention and control groups (RR 0.94, 95% CI 0.76 to 1.18; 2 studies; 7256 participants; high-certainty evidence).
  • Small improvement in composite Z-score for cognitive function on a neuropsychological test battery (MD 0.03, 95% CI 0.01 to 0.06; 3 studies; 4617 participants; high-certainty evidence), and on the MoCA (MD 0.76 point, 95% CI 0.05 to 1.46; 2 studies; 1554 participants; very low-certainty evidence).
  • No evidence of an effect on MMSE (MD 0.02 point, 95% CI -0.06 to 0.09; 6 studies; 8697 participants; moderate-certainty evidence) or on mortality (RR 0.93, 95% CI 0.84 to 1.04; 4 studies; 11,487 participants; high-certainty evidence).
  • High-certainty evidence for an interaction with ApoE4 status on NTB cognitive function (carriers MD 0.14, 95% CI 0.04 to 0.25; noncarriers MD 0.04, 95% CI -0.02 to 0.10; P for interaction 0.09); no clear interaction with baseline MMSE (P for interaction 0.12) or clear effect in those with CAIDE score > 6 (MD 0.07, 95% CI -0.00 to 0.15).

Methods

  • Systematic review and random-effects meta-analysis of RCTs; multi-domain intervention defined as more than one component (pharmacological or non-pharmacological), excluding two or more drugs with the same therapeutic target; controls were sham intervention or usual care.
  • Searched ALOIS, MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, LILACS, and ClinicalTrials.gov on 28 April 2021; required ≥400 participants and ≥12 months intervention/follow-up.
  • Two review authors independently screened, extracted data, assessed risk of bias, and applied GRADE; effects expressed as risk ratios and mean differences with 95% CIs.

Limitations

  • Stated: incident dementia conclusions rest on only two trials; cognitive assessment was very heterogeneous (from full neuropsychological batteries to short screening tests); interventions varied in components and intensity; the NTB effect was strongest in trials offering cognitive training, making a learning effect difficult to rule out.
  • Stated: MoCA evidence was very low certainty due to serious risk of bias, inconsistency, and indirectness.
  • Evident from the text: intervention durations ranged widely (12 months to 10 years), and the review's conclusions on dementia prevention are limited by the small number of trials reporting that outcome.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1002/14651858.cd013572.pub2

Cites

127 of 127 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

  • Findingown data
    § Abstract

    There was no clear evidence for an interaction with baseline cognitive status (defined by MMSE score) on cognitive function measured with an NTB (low baseline MMSE group MD 0.06, 95% CI 0.01 to 0.11; high baseline MMSE group MD 0.01, 95% CI -0.01 to 0.04; P for interaction 0.12).

    “There was no clear evidence for an interaction with baseline cognitive status (defined by MMSE-score) on cognitive function measured with an NTB (low baseline MMSE group MD 0.06, 95% CI 0.01 to 0.11, high baseline MMSE group MD 0.01, 95% CI -0.01 to 0.04, P for interaction 0.12)”
    Quote in the paperNot a substantial claim
  • Findingown data
    § Abstract

    There was no evidence of an effect of multi-domain interventions on the MMSE (MD 0.02 point, 95% CI -0.06 to 0.09; 6 studies; 8697 participants; moderate-certainty evidence).

    “there was no evidence of an effect on the MMSE (MD 0.02 point, 95% CI -0.06 to 0.09; 6 studies; 8697participants; moderate-certainty evidence)”
    Quote in the paperSubstantial claim
  • Findingown data
    § Abstract

    There was no clear evidence for an effect of multi-domain interventions in participants with a CAIDE score greater than 6 points (MD 0.07, 95% CI -0.00 to 0.15).

    “nor was there clear evidence for an effect in participants with a Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score > 6 points (MD 0.07, 95%CI -0.00 to 0.15).”
    Quote in the paperNot a substantial claim
  • Findingown data
    § Abstract

    Nine randomised controlled trials with 18,452 participants were included in this review.

    “We included nine RCTs (18.452 participants) in this review.”
    Quote in the paperSubstantial claim
  • Findingown data
    § Abstract

    There was no evidence of an effect of multi-domain interventions on mortality (RR 0.93, 95% CI 0.84 to 1.04; 4 studies; 11,487 participants; high-certainty evidence).

    “There was no evidence of an effect on mortality (RR 0.93, 95% CI 0.84 to 1.04; 4 studies; 11,487 participants; high-certainty evidence).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 2
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 7

  • May combine two claims.

    Findingown data
    § Abstract

    There was a small difference in cognitive function measured with the Montreal Cognitive Assessment (MoCA) scale favouring multi-domain interventions (MD 0.76 point, 95% CI 0.05 to 1.46; 2 studies; 1554 participants), but the certainty of evidence for the MoCA was very low.

    “and with the Montreal Cognitive Assessment (MoCA) scale (MD 0.76 point, 95% CI 0.05 to 1.46; 2 studies; 1554 participants), but the certainty of evidence for the MoCA was very low (due to serious risk of bias, inconsistency and indirectness)”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data
    § Abstract

    There was a small difference in composite Z-score for cognitive function measured with a neuropsychological test battery (NTB) favouring multi-domain interventions (MD 0.03, 95% CI 0.01 to 0.06; 3 studies; 4617 participants; high-certainty evidence).

    “There was a small improvement in cognitive function assessed by a NTB in the group of participants receiving a multi-domain intervention”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given
    § Abstract

    The interventions in the included studies were diverse in terms of their components and intensity.

    “Interventions were diverse in terms of their components and intensity.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data
    § Abstract

    Assessment of cognitive functioning was very heterogeneous across the included studies, ranging from complete neuropsychological assessments to short screening tests such as the MMSE.

    “Assessment of cognitive functioning was very heterogeneous across studies, ranging from complete neuropsychological assessments to short screening tests such as the mini-mental state examination (MMSE).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data
    § Abstract

    The duration of the interventions in the included studies varied from 12 months to 10 years.

    “The duration of the interventions varied from 12 months to 10 years.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Abstract

    Of the nine included studies, two reported incident dementia as an outcome and all nine reported a measure of cognitive functioning.

    “Two studies reported incident dementia as an outcome; all nine studies reported a measure for cognitive functioning.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data
    § Abstract

    Data were extracted independently by at least two review authors.

    “At least two review authors also independently extracted data, assessed the risk of bias and applied the GRADE approach to assess the certainty of evidence.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data
    § Abstract

    Risk of bias was assessed independently by at least two review authors.

    “At least two review authors also independently extracted data, assessed the risk of bias and applied the GRADE approach to assess the certainty of evidence.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given
    § Abstract

    The identified citations were screened against the inclusion criteria by two review authors working independently.

    “We screened the identified citations against inclusion criteria by two review authors working independently.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data
    § Abstract

    The GRADE approach was applied by at least two review authors to assess the certainty of evidence.

    “At least two review authors also independently extracted data, assessed the risk of bias and applied the GRADE approach to assess the certainty of evidence.”
    Quote in the paperNot a substantial claim
10 of 10

  • The paper relies on this without support.

    Up to 40% of dementia is attributable to potentially modifiable risk factors.

    “Up to 40% of dementia is attributable to potentially modifiable risk factors”

  • The paper relies on this without support.

    Sporadic dementia is a multifactorial condition deriving from multiple causes and risk factors.

    “Since sporadic dementia is a multifactorial condition, thought to derive from multiple causes and risk factors”

  • The paper relies on this without support.

    Multi-domain interventions may be more effective for the prevention of dementia than interventions targeting single risk factors.

    “multi-domain interventions may be more effective for the prevention of dementia than those targeting single risk factors”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • A 2021 Cochrane review identified nine multi-domain intervention RCTs for prevention of dementia or cognitive decline with 18,452 participants.

    “A 2021 Cochrane review identified nine multi-domain interventions for the prevention of dementia or cognitive decline RCTs with 18,452 participants.(260)”

    From Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission (2024) · cites this paper as [260]

    The Abstract says the review included RCTs of multi-domain interventions assessing cognitive functioning or incident dementia. It does not give a count of nine trials or 18,452 participants; searches for those numbers and the trial count found no matching passage in our copy. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • There was high certainty of a small benefit on overall cognition (MD 0.03, 0.01-0.06) in 3 RCTs with n=4,617 over 18-36 months.

    “There was high certainty of a small benefit on overall cognition (3 RCTs; composite z score mean difference (MD) 0.03, 0.01- 0.06, n = 4,617, over 18-36 months), (228, 261, 262)”

    From Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission (2024) · cites this paper as [260]

    No passage in our copy addresses the reported benefit on overall cognition, its certainty, the effect estimate, or the trial count. Searches for the composite z score, 4,617 participants, 0.03, and global cognitive function returned no relevant passage, so the claim cannot be checked against our copy. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

  • The benefit on overall cognition was particularly in people with the APOE ε4 genotype (carriers MD 0.14, 0.04-0.25; noncarriers MD 0.04, -0.02 to 0.10) in 2 RCTs n=2,043.

    “particularly in people with the APOE ε 4 genotype (2 RCTs; n = 2,043, follow-up 24-36 months, carriers MD 0.14, 0.04 -0.25, noncarriers MD 0.04, -0.02 to 0.10,)”

    From Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission (2024) · cites this paper as [260]

    No passage in our indexed copy reports an APOE ε4 subgroup analysis, the cited carrier and noncarrier mean differences, or the stated two RCTs and 2,043 participants. Searches for APOE, apolipoprotein E, the numerical estimates, and genotype subgroup effects found no passage that verifies the claim. (LLM, conf=0.70)

    Experimental — accuracy not yet measured

  • In a UKB study of 300,823 people, those with cataracts had an increased risk of dementia (HR 1.2, 1.01-1.46).

    “Although a UKB study of 300,823 people found that those with cataracts had an increased risk of dementia (HR, 1.2, 1.01 -1.46)”

    From Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission (2024) · cites this paper as [255]

    No passage from our copy addresses cataracts or a UK Biobank study of 300,823 people. Searches for cataract, the sample size, visual impairment, and the reported hazard ratio found no matching evidence; the retrieved Abstract describes a review of multi-domain interventions instead. (LLM, conf=0.74)

    Experimental — accuracy not yet measured

  • In the UKB study, there was no difference in dementia risk between those who had cataract surgery and healthy controls.

    “but that there was no difference in dementia risk between those who had cataract surgery and healthy controls.(255)”

    From Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission (2024) · cites this paper as [255]

    No passage in our copy addresses cataract surgery or a UK Biobank comparison with healthy controls. Searches for cataract, surgery, and the claimed dementia-risk comparison returned no relevant passage; the retrieved Abstract passage describes multi-domain intervention trials instead. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

Cites

1 retracted

Flagged first, then by citations

1 of the 128 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Related

Authors
Hafdi, M., Hoevenaar-Blom, M. P., & Richard, E.
Affiliations
  • Amsterdam University Medical Centers (NL)
  • Department of Public and Occupational Health; Amsterdam UMC, University of Amsterdam; Amsterdam Netherlands
  • Radboud University Nijmegen (NL)
ORCID
Venue
Cochrane Database of Systematic Reviews
Publisher
Wiley
Published
2021-11-08
Volume
2021
Issue
11
ISSN
  • 1361-6137 (ISSN-L)
  • 1465-1858
DOI
10.1002/14651858.cd013572.pub2
OpenAlex
W4200308390
Cited by
124
References
128
Citations by year
2026: 21 · 2025: 33 · 2024: 30 · 2023: 27 · 2022: 11 · 2021: 2
FWCI
3.13
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Cochrane Database of Systematic Reviews (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
  • Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
Keywords
dementia prevention, cognitive decline, multidomain intervention, older adults, mild cognitive impairment, dementia risk factors, lifestyle intervention, cognitive function, incident dementia, mortality, adverse events, cardiovascular events, risk of bias, quality of evidence, citizen science, non-pharmacological treatment, pharmacological interventions

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review