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@ARTICLE{Cash:279454,
      author       = {Cash, David M and Morgan, Katy E and O'Connor, Antoinette
                      and Veale, Thomas D and Malone, Ian B and Poole, Teresa and
                      Benzinger, Tammie Ls and Gordon, Brian A and Ibanez, Laura
                      and Li, Yan and Llibre-Guerra, Jorge J and McDade, Eric and
                      Wang, Guoqiao and Chhatwal, Jasmeer P and Day, Gregory S and
                      Huey, Edward and Jucker, Mathias and Levin, Johannes and
                      Niimi, Yoshiki and Noble, James M and Roh, Jee Hoon and
                      Sánchez-Valle, Racquel and Schofield, Peter R and Bateman,
                      Randall J and Frost, Chris and Fox, Nick C},
      collaboration = {Network, Dominantly Inherited Alzheimer},
      title        = {{S}ample size estimates for biomarker-based outcome
                      measures in clinical trials in autosomal dominant
                      {A}lzheimer's disease.},
      journal      = {The journal of prevention of Alzheimer's disease},
      volume       = {12},
      number       = {6},
      issn         = {2274-5807},
      address      = {Cham},
      publisher    = {Springer International Publishing},
      reportid     = {DZNE-2025-00781},
      pages        = {100133},
      year         = {2025},
      abstract     = {Alzheimer disease (AD)-modifying therapies are approved for
                      treatment of early-symptomatic AD. Autosomal dominant AD
                      (ADAD) provides a unique opportunity to test therapies in
                      presymptomatic individuals.Using data from the Dominantly
                      Inherited Alzheimer Network (DIAN), sample sizes for
                      clinical trials were estimated for various cognitive,
                      imaging, and CSF outcomes. Sample sizes were computed for
                      detecting a reduction of either absolute levels of
                      AD-related pathology (amyloid, tau) or change over time in
                      neurodegeneration (atrophy, hypometabolism, cognitive
                      change).Biomarkers measuring amyloid and tau pathology had
                      required sample sizes below 200 participants per arm
                      (examples CSF Aβ42/40: 47[95 $\%CI$ 25,104], cortical PIB
                      49[28,99], CSF p-tau181 74[48,125]) for a four-year trial in
                      presymptomatic individuals (CDR=0) to have 80 $\%$ power (5
                      $\%$ statistical significance) to detect a 25 $\%$ reduction
                      in absolute levels of pathology, allowing 40 $\%$ dropout.
                      For cognitive, MRI, and FDG, it was more appropriate to
                      detect a 50 $\%$ reduction in rate of change. Sample sizes
                      ranged from 250 to 900 (examples hippocampal volume:
                      338[131,2096], cognitive composite: 326[157,1074]). MRI, FDG
                      and cognitive outcomes had lower sample sizes when including
                      indivduals with mild impairment (CDR=0.5 and 1) as well as
                      presymptomatic individuals (CDR=0).Despite the rarity of
                      ADAD, presymptomatic clinical trials with feasible sample
                      sizes given the number of cases appear possible.},
      keywords     = {Humans / Alzheimer Disease: genetics / Alzheimer Disease:
                      cerebrospinal fluid / Alzheimer Disease: diagnosis /
                      Alzheimer Disease: diagnostic imaging / Alzheimer Disease:
                      pathology / Biomarkers: cerebrospinal fluid / Amyloid
                      beta-Peptides: cerebrospinal fluid / Sample Size / tau
                      Proteins: cerebrospinal fluid / Male / Female / Clinical
                      Trials as Topic / Outcome Assessment, Health Care / Magnetic
                      Resonance Imaging / Positron-Emission Tomography / Brain:
                      pathology / Brain: diagnostic imaging / Middle Aged /
                      Alzheimer's disease (Other) / Autosomal dominant (Other) /
                      CSF (Other) / Clinical trials (Other) / Linear mixed effects
                      models (Other) / Longitudinal (Other) / MRI (Other) / PET
                      (Other) / Sample size (Other) / ß-amyloid (Other) /
                      Biomarkers (NLM Chemicals) / Amyloid beta-Peptides (NLM
                      Chemicals) / tau Proteins (NLM Chemicals)},
      cin          = {AG Jucker / Clinical Research (Munich) / AG Levin},
      ddc          = {610},
      cid          = {I:(DE-2719)1210001 / I:(DE-2719)1111015 /
                      I:(DE-2719)1111016},
      pnm          = {352 - Disease Mechanisms (POF4-352) / 353 - Clinical and
                      Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40118731},
      doi          = {10.1016/j.tjpad.2025.100133},
      url          = {https://pub.dzne.de/record/279454},
}