Evidence map›Paper›PMID 33741639›Full record

ArticleNeurology2021

Long-term Effects of Cholinesterase Inhibitors on Cognitive Decline and Mortality.

Hong Xu, Sara Garcia-Ptacek, Linus Jönsson, Anders Wimo, Peter Nordström, Maria Eriksdotter

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07093684 (Dementia and Kidney Disease), which is not on this map. Cited by 82 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed, 2 pooled it
19.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT07093684 active not recruitingnot on this map

Dementia and Kidney Disease: Epidemiological Approaches to Risk Factors and Treatment Strategies

Typeobservational_patient_registrySponsorKarolinska InstitutetRan2007 to 2026Enrolled200,000ConditionsChronic Kidney Disease, Acute Kidney Injuries, Real World Study, DementiaArmsKidney disease
3 · Its place in the literature

Who cites it

82 citing papers in PubMed, 2 syntheses or guidelines pooled it, 168 citations in OpenAlex.

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  20. COVID-19 Factors Associated With Medication Changes Among Nursing Home Residents With Dementia.Journal of applied gerontology : the official journal of the Southern Gerontological Society · 2026
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22 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Hong XuFrom the Division of Clinical Geriatrics (H.X., S.G.-P., M.E.), Division of Neurogeriatrics (L.J., A.W.), Department of Neurobiology, Care Sciences and Society, and Department of Medical Epidemiology and Biostatistics (H.X.), Karolinska Institutet; Department of Internal Medicine (S.G.-P.), Neurology Section, Södersjukhuset, Stockholm, Sweden; H. Lundbeck A/S (L.J.), Copenhagen, Denmark; Department of Community Medicine and Rehabilitation (P.N.), Geriatric Medicine, Umeå University; and Theme Aging (S.G.-P., M.A.), Karolinska University Hospital, Stockholm, Sweden. hong.xu.2@ki.se.
Sara Garcia-PtacekFrom the Division of Clinical Geriatrics (H.X., S.G.-P., M.E.), Division of Neurogeriatrics (L.J., A.W.), Department of Neurobiology, Care Sciences and Society, and Department of Medical Epidemiology and Biostatistics (H.X.), Karolinska Institutet; Department of Internal Medicine (S.G.-P.), Neurology Section, Södersjukhuset, Stockholm, Sweden; H. Lundbeck A/S (L.J.), Copenhagen, Denmark; Department of Community Medicine and Rehabilitation (P.N.), Geriatric Medicine, Umeå University; and Theme Aging (S.G.-P., M.A.), Karolinska University Hospital, Stockholm, Sweden.
Linus JönssonFrom the Division of Clinical Geriatrics (H.X., S.G.-P., M.E.), Division of Neurogeriatrics (L.J., A.W.), Department of Neurobiology, Care Sciences and Society, and Department of Medical Epidemiology and Biostatistics (H.X.), Karolinska Institutet; Department of Internal Medicine (S.G.-P.), Neurology Section, Södersjukhuset, Stockholm, Sweden; H. Lundbeck A/S (L.J.), Copenhagen, Denmark; Department of Community Medicine and Rehabilitation (P.N.), Geriatric Medicine, Umeå University; and Theme Aging (S.G.-P., M.A.), Karolinska University Hospital, Stockholm, Sweden.
Anders WimoFrom the Division of Clinical Geriatrics (H.X., S.G.-P., M.E.), Division of Neurogeriatrics (L.J., A.W.), Department of Neurobiology, Care Sciences and Society, and Department of Medical Epidemiology and Biostatistics (H.X.), Karolinska Institutet; Department of Internal Medicine (S.G.-P.), Neurology Section, Södersjukhuset, Stockholm, Sweden; H. Lundbeck A/S (L.J.), Copenhagen, Denmark; Department of Community Medicine and Rehabilitation (P.N.), Geriatric Medicine, Umeå University; and Theme Aging (S.G.-P., M.A.), Karolinska University Hospital, Stockholm, Sweden.
Peter NordströmFrom the Division of Clinical Geriatrics (H.X., S.G.-P., M.E.), Division of Neurogeriatrics (L.J., A.W.), Department of Neurobiology, Care Sciences and Society, and Department of Medical Epidemiology and Biostatistics (H.X.), Karolinska Institutet; Department of Internal Medicine (S.G.-P.), Neurology Section, Södersjukhuset, Stockholm, Sweden; H. Lundbeck A/S (L.J.), Copenhagen, Denmark; Department of Community Medicine and Rehabilitation (P.N.), Geriatric Medicine, Umeå University; and Theme Aging (S.G.-P., M.A.), Karolinska University Hospital, Stockholm, Sweden.
Maria EriksdotterFrom the Division of Clinical Geriatrics (H.X., S.G.-P., M.E.), Division of Neurogeriatrics (L.J., A.W.), Department of Neurobiology, Care Sciences and Society, and Department of Medical Epidemiology and Biostatistics (H.X.), Karolinska Institutet; Department of Internal Medicine (S.G.-P.), Neurology Section, Södersjukhuset, Stockholm, Sweden; H. Lundbeck A/S (L.J.), Copenhagen, Denmark; Department of Community Medicine and Rehabilitation (P.N.), Geriatric Medicine, Umeå University; and Theme Aging (S.G.-P., M.A.), Karolinska University Hospital, Stockholm, Sweden.
Lundbeck (Denmark) · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo investigate whether cholinesterase inhibitors (ChEIs) are associated with slower cognitive decline in Alzheimer dementia and decreased risk of severe dementia or death.

methodsPatients with Alzheimer dementia from the Swedish Dementia Registry starting on ChEIs within 3 months of the dementia diagnosis were included and compared to nontreated patients with Alzheimer dementia. In a propensity score-matched cohort, the association between ChEI use and cognitive trajectories assessed by Mini-Mental State Examination (MMSE) scores was examined with a mixed model, and severe dementia (MMSE score <10) or death as an outcome was assessed with Cox proportional hazards models.

resultsThe matched cohort included 11,652 ChEI users and 5,826 nonusers. During an average of 5 years of follow-up, 255 cases developed severe dementia, and 6,055 (35%) died. ChEI use was associated with higher MMSE score at each visit (0.13 MMSE points per year; 95% confidence interval [CI] 0.06-0.20). ChEI users had a 27% lower risk of death (0.73, 95% CI 0.69-0.77) compared with nonusers. Galantamine was associated with lower risk of death (0.71, 95% CI 0.65-0.76) and lower risk of severe dementia (0.69, 95% CI 0.47-1.00) and had the strongest effect on cognitive decline of all the ChEIs (0.18 MMSE points per year, 95% CI 0.07-0.28).

conclusionsChEIs are associated with cognitive benefits that are modest but persist over time and with reduced mortality risk, which could be explained partly by their cognitive effects. Galantamine was the only ChEI demonstrating a significant reduction in the risk of developing severe dementia. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with Alzheimer dementia ChEIs decrease long-term cognitive decline and risk of death and that galantamine decreases the risk of severe dementia.

Indexed as

AgedAged, 80 and overAlzheimer DiseaseCholinesterase InhibitorsCognitive DysfunctionCohort StudiesFemaleHumansMaleMental Status and Dementia TestsProportional Hazards ModelsTimeCholinesterase Inhibitors

Identifiers

PMID33741639
PMCPMC8166426
OpenAlexW3138811377

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.