Observational studyAlzheimer's research & therapy2016
Mild versus moderate stages of Alzheimer's disease: three-year outcomes in a routine clinical setting of cholinesterase inhibitor therapy.
Observational study in Alzheimer's research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Real-World Use of Symptomatic Treatments in Early Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2023Pooled it
- Rewiring mTOR signaling in Alzheimer's disease: emerging mTOR modulators beyond oncology.Bioscience reports · 2026Review
- Recent Advances and Future Directions in Alzheimer's Disease Genetic Research.International journal of molecular sciences · 2025Review
- Enhancing aptamer selection in alzheimer's disease: integrating structure prediction and molecular dynamics simulations.Scientific reports · 2025Article
- Synthesis, biological activities and computational studies of bis-Schiff base derivatives of 4-hydroxyacetophenone: insights from anRSC advances · 2025Article
- Efficacy ofFrontiers in neurology · 2025Article
- Difference in trajectories according to early amyloid accumulation in cognitively unimpaired elderly.European journal of neurology · 2024Article
- AlzDiscovery: A computational tool to identify Alzheimer's disease-causing missense mutations using protein structure information.Protein science : a publication of the Protein Society · 2024Article
- Epigenetic Alterations in Alzheimer's Disease: Impact on Insulin Signaling and Advanced Drug Delivery Systems.Biology · 2024Review
- Evaluating Elements of the Care Partner Experience in Individuals Who Care for People with Alzheimer's Disease Across the Severity Spectrum.Neurology and therapy · 2024Article
- Review
- Phytochemicals: A Promising Alternative for the Prevention of Alzheimer's Disease.Life (Basel, Switzerland) · 2023Review
- Extracellular Vesicles, Cell-Penetrating Peptides and miRNAs as Future Novel Therapeutic Interventions for Parkinson's and Alzheimer's Disease.Biomedicines · 2023Review
- Alzheimer's Disease: A Brief History of Immunotherapies Targeting Amyloid β.International journal of molecular sciences · 2023Review
- miRNAs and Stem Cells as Promising Diagnostic and Therapeutic Targets for Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2023Review
- Pilot Randomized, Double-Blind, Placebo-Controlled Crossover Trial Evaluating the Feasibility of an Intranasal Oxytocin in Improving Social Cognition in Individuals Living with Alzheimer's Disease.Journal of Alzheimer's disease reports · 2023Article
- The Molecular Effects of Environmental Enrichment on Alzheimer's Disease.Molecular neurobiology · 2022Review
- Interdisciplinary Approaches to Deal with Alzheimer's Disease-From Bench to Bedside: What Feasible Options Do Already Exist Today?Biomedicines · 2022Review
- Advances on Therapeutic Strategies for Alzheimer's Disease: From Medicinal Plant to Nanotechnology.Molecules (Basel, Switzerland) · 2022Review
- Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThere is an increasing interest in cognitive and functional outcomes in the respective stages of Alzheimer's disease (AD) and in novel therapies particularly for the milder phases of AD. Our aim was to describe and compare various aspects of disease progression in patients with mild versus moderate AD in routine clinical practice of cholinesterase inhibitor (ChEI) therapy.
methodsThis 3-year, prospective, observational, multicentre study included 1021 participants. Of these, 734 had mild AD (Mini-Mental State Examination (MMSE) score, 20-26) and 287 had moderate AD (MMSE score, 10-19) at the start of ChEI treatment. At baseline and every 6 months, patients were assessed using cognitive, global, instrumental and basic activities of daily living (ADL) scales. Potential predictors of deterioration in moderate AD were analysed using mixed-effects models.
resultsThe change from baseline between participants with mild and moderate stages of AD after 3 years of ChEI therapy differed significantly on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and basic ADL, but not using the MMSE and instrumental ADL scales. Protective independent factors for better cognitive long-term outcome in the group with moderate AD were older age, higher instrumental ADL ability, no antipsychotics, usage of non-steroidal anti-inflammatory drugs/acetylsalicylic acid, living with family member, lower education and a higher mean dose of ChEI. Apolipoprotein E genotype did not influence the rates of disease progression or the longitudinal outcomes. Prediction models were provided for moderate AD.
conclusionsMore sensitive cognitive measures, such as the ADAS-cog scale, are required to detect a possibly faster deterioration among the participants with moderate AD. This study highlighted the clinical importance of instrumental ADL evaluations in patients at a mild stage of AD, and the importance of optimizing the ChEI dose even for individuals with moderate AD. Solitary living was a risk factor for faster cognitive decline, and probably expanded the need for formal care in the group with moderate AD. The patients with more advanced AD and presumably more pronounced neuroinflammation might have additional cognitive benefits from longer-term treatment with anti-inflammatory drugs.
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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.