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Publications

Journal Article Ahead of print

PubMed: 42928321 DOI: 10.1007/s10654-026-01470-7

Developing a microsimulation model of Alzheimer's disease for the evaluation of disease modifying therapies.

Eur J Epidemiol

Authors: Pieter J van der Veere, Hana M Broulíková, Jeroen Hoogland, Ron Handels, Everard G B Vijverberg, Argonde C van Harten, Charlotte E Teunissen, Frederik Barkhof, Elsmarieke van de Giessen, Wiesje M van der Flier, Johannes Berkhof

Affiliations

  • Amsterdam Neuroscience, De Boelelaan 1117, 1081, Amsterdam, HV, The Netherlands.
  • Alzheimer Center Amsterdam, Department of Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, De Boelelaan 1118, 1081, Amsterdam, HZ, The Netherlands.
  • Department of Epidemiology and Data Science, Amsterdam UMC, De Boelelaan 1117, 1081, Amsterdam, HV, The Netherlands.
  • Alzheimer Center Amsterdam, Department of Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, De Boelelaan 1118, 1081, Amsterdam, HZ, The Netherlands.
  • Department of Health Sciences, Faculty of Science, Vrije Universiteit Amsterdam, Van Der Boechorststraat 7, 1081, Amsterdam, BT, Netherlands.
  • National Institute of Mental Health, Topolová 748, 250 67, Klecany, Czech Republic.
  • Department of Epidemiology and Data Science, Amsterdam UMC, De Boelelaan 1117, 1081, Amsterdam, HV, The Netherlands.
  • Alzheimer Center Limburg, Mental Health and Neuroscience Research Institute, Maastricht University, Maastricht, Netherlands.
  • Division of Neurogeriatrics, Department for Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Solnavägen 1, Solna, 171 77, Stockholm, Sweden.
  • Amsterdam Neuroscience, De Boelelaan 1117, 1081, Amsterdam, HV, The Netherlands.
  • Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, De Boelelaan 1118, 1081, Amsterdam, HZ, The Netherlands.
  • UCL Centre for Medical Image Computing, Department of Computer Science, University College London, London, WC1N 3BG, UK.
  • Department of Radiology & Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam University Medical Center, De Boelelaan 1117, 1081, Amsterdam, HV, The Netherlands.

Abstract

Clinical trials of amyloid-targeting therapies (ATTs) for Alzheimer's Disease (AD) showed slowing of decline in continuous cognitive and functional outcomes over eighteen months of follow-up. Existing simulation models used to extrapolate these results do not account for the distinct but correlated trajectories of cognitive and functional decline, limiting their accuracy in evaluating ATT effects on both domains. We developed an AD microsimulation model using an amyloid-positive memory clinic population that can translate slowed cognitive decline into effects on clinical functional independence stages. The model contained stages of mild cognitive impairment (MCI), community dementia, institutionalisation, and death. The transitions from MCI to dementia and from dementia to institutionalisation or death were related to Mini-Mental State Examination (MMSE) measurements through statistical joint models. Model validation showed that observed and predicted cumulative incidence curves overlapped for all stage transitions, indicating an accurate description of time in each stage. An untreated cohort starting with MCI had a mean duration of MCI, mild, moderate and severe community dementia, and institutionalisation of 3.3, 2.3, 1.6, 1.1, and 1.7 years, respectively, totalling 10.0 years. When ATTs slowed MMSE decline by 30% during MCI and mild dementia (community dementia with an MMSE above 20), the duration of MCI and mild dementia was prolonged by 0.4 and 1.0 years, respectively, and institutionalisation was delayed by 1.1 year. The time institutionalised remained similar. Our AD microsimulation model can translate ATT effects on cognition into effects on functional independence and can be used to assess the cost-effectiveness of new therapies.

MeSH

Dementia, Epidemiology, Alzheimer Disease, Cognitive Dysfunction, Therapeutics, Amyloid