Evidence map›Paper›PMID 41396413›Full record

ArticleGeroScience2026

Effectiveness of acetylcholinesterase inhibitors and memantine in patients affected by severe dementia.

Giovanni Zuliani, Gloria Brombo, Tommaso Romagnoli, Michele Polastri, Francesco di Paola Dario, Marco Zuin

Abstract read
In one paragraph

Article in GeroScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. A phase 1, safety, tolerability, and pharmacokinetics study of bisnorcymserine, a highly selective inhibitor of butyrylcholinesterase.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Trial
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Giovanni ZulianiDepartment of Translational Medicine and for Romagna, University of Ferrara, Via Savonarola 9, 44121, Ferrara, Italy.
Gloria BromboDepartment of Translational Medicine and for Romagna, University of Ferrara, Via Savonarola 9, 44121, Ferrara, Italy. brmglr@unife.it.ORCID http://orcid.org/0000-0003-3907-0770
Tommaso RomagnoliDepartment of Translational Medicine and for Romagna, University of Ferrara, Via Savonarola 9, 44121, Ferrara, Italy.
Michele PolastriDepartment of Translational Medicine and for Romagna, University of Ferrara, Via Savonarola 9, 44121, Ferrara, Italy.
Francesco di Paola DarioDepartment of Translational Medicine and for Romagna, University of Ferrara, Via Savonarola 9, 44121, Ferrara, Italy.ORCID http://orcid.org/0009-0007-5103-4496
Marco ZuinDepartment of Translational Medicine and for Romagna, University of Ferrara, Via Savonarola 9, 44121, Ferrara, Italy.

Funding

National Alzheimer's Coordinating CenterU24AG072122 · NIA · UNIVERSITY OF WASHINGTON · PI STEPHENS, KARI A · 2021 to 2025
$45.8M
Research Education ComponentP30AG062422 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Katherine P Rankin · 2019 to 2026
$36.9M
Research Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI BRADFORD C DICKERSON · 2019 to 2026
$36.5M
UCSD Shiley-Marcos Alzheimer's Disease Research Center P30P30AG062429 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DOUGLAS R GALASKO · 2019 to 2026
$34.9M
Wisconsin Alzheimer's Disease Research CenterP30AG062715 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Sanjay Asthana · 2019 to 2026
$34.5M
Research Education ComponentP30AG062677 · NIA · MAYO CLINIC ROCHESTER · PI KEJAL KANTARCI · 2019 to 2026
$33.5M
Research Education ComponentP30AG066514 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Margaret Sewell · 2020 to 2026
$31.0M
Yale Alzheimer Disease Research CenterP30AG066508 · NIA · YALE UNIVERSITY · PI STEPHEN M STRITTMATTER · 2020 to 2026
$30.2M
Research Education CoreP30AG066462 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI PHILIP L DE JAGER · 2020 to 2026
$30.1M
Research Education ComponentP30AG066468 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI C. Elizabeth Shaaban · 2020 to 2026
$29.4M
Research Education ComponentP30AG066507 · NIA · JOHNS HOPKINS UNIVERSITY · PI Corinne Pettigrew · 2020 to 2026
$29.3M
University of Washington Alzheimer's Disease Research CenterP30AG066509 · NIA · UNIVERSITY OF WASHINGTON · PI Amanda D. Boyd · 2020 to 2026
$29.0M
NIA NIH HHS P20 AG068082NIA NIH HHS P30 AG062421NIA NIH HHS P30 AG062422NIA NIH HHS P30 AG062429NIA NIH HHS P30 AG062677NIA NIH HHS P30 AG062715NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066462NIA NIH HHS P30 AG066468NIA NIH HHS P30 AG066506NIA NIH HHS P30 AG066507NIA NIH HHS P30 AG066508NIA NIH HHS P30 AG066509NIA NIH HHS P30 AG066511NIA NIH HHS P30 AG066512NIA NIH HHS P30 AG066514NIA NIH HHS P30 AG066515NIA NIH HHS P30 AG066518NIA NIH HHS P30 AG066519NIA NIH HHS P30 AG066530NIA NIH HHS P30 AG066546NIA NIH HHS P30 AG072931NIA NIH HHS P30 AG072946NIA NIH HHS P30 AG072947NIA NIH HHS P30 AG072958NIA NIH HHS P30 AG072959NIA NIH HHS P30 AG072972NIA NIH HHS P30 AG072973NIA NIH HHS P30 AG072975NIA NIH HHS P30 AG072976NIA NIH HHS P30 AG072977NIA NIH HHS P30 AG072978NIA NIH HHS P30 AG072979NIA NIH HHS P30 AG086401NIA NIH HHS P30 AG086404NIA NIH HHS R01 AG079280NIA NIH HHS U24 AG072122
6 · The paper itself

Abstract

The efficacy of acetylcholinesterase inhibitors (AChEI) and memantine (ME) in severe dementia remains uncertain, and real world data are limited. We evaluated the progression of cognitive decline and mortality rates in a cohort of outpatients with severe dementia treated with AChEI and/or ME or not treated, from the National Alzheimer's Coordinating Center Uniform Data Set (NACC-UDS). Overall, 703 patients (mean age:78.3 ± 7.2 years; females:56.1%) with severe dementia (Mini-Mental State Examination-MMSE ≤ 10/30) were included [407 late-onset Alzheimer's disease (LOAD), 126 Lewy body dementia (LBD), 170 vascular dementia (VD)]. Patients were grouped by treatment status: untreated (AChEI - /ME - ; n.70), AChEI only (AChEI + ; n.294), ME only (ME + ; n.215), combined therapy (AChEI + /ME + ; n.124). During follow-up (mean:1.7 ± 0.3 years; range:0.2-2.9 years) the mean MMSE scores declined by - 1.7 points (Standard Deviation: -1.55 to -1.9) in AChEI - /ME - (p for trend:0.001), - 1.5 points (-1.55 to -1.9) in AChEI + (p:0.001), - 0.7 points (-0.5 to -0.9) in ME + (p:0.09), while it increased by + 0.7 points (+ 0.4 to + 1.0) in AChEI + /ME + (p:0.001). Survival rates were 8% in AChEI - /ME - , 10% in AChEI + , 28% in ME + , and 49% in AChEI + /ME + . In Cox proportional hazards analysis (age and sex adjusted), AChEI + /ME + exhibited a 39% reduction in total mortality compared with no treatment (HR:0.61; 95%CI:0.49-0.77; p < 0.001), ME + displayed a 22% reduction (HR:0.78; 95%CI:0.65-0.94; p:0.007), while AChEI + showed no association (HR:0.97; 95%CI:0.80-1.18; p:0.75). When the Cox proportional hazards models were stratified by dementia subtype, consistent significant patterns were observed in LOAD and LBD. In this real-world cohort of older adults with severe dementia, the combination therapy (ME + AchEI) seems to be associated with the best outcomes, including a stabilization of cognitive function and reduced total mortality.

Indexed as

Cholinesterase InhibitorsDementiaMemantineAgedAged, 80 and overAlzheimer DiseaseDisease ProgressionDrug Therapy, CombinationFemaleHumansMaleSeverity of Illness IndexTreatment OutcomeCholinesterase InhibitorsMemantineAcetylcholinesterase inhibitorsAlzheimer’s diseaseCognitive declineDementiaMemantine

Identifiers

PMID41396413
PMCPMC13601481

What OpenQuestion holds

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Registered trials

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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.