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001     279454
005     20250720001558.0
024 7 _ |a 10.1016/j.tjpad.2025.100133
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024 7 _ |a 2274-5807
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037 _ _ |a DZNE-2025-00781
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Cash, David M
|b 0
245 _ _ |a Sample size estimates for biomarker-based outcome measures in clinical trials in autosomal dominant Alzheimer's disease.
260 _ _ |a Cham
|c 2025
|b Springer International Publishing
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520 _ _ |a 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.
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650 _ 7 |a Alzheimer's disease
|2 Other
650 _ 7 |a Autosomal dominant
|2 Other
650 _ 7 |a CSF
|2 Other
650 _ 7 |a Clinical trials
|2 Other
650 _ 7 |a Linear mixed effects models
|2 Other
650 _ 7 |a Longitudinal
|2 Other
650 _ 7 |a MRI
|2 Other
650 _ 7 |a PET
|2 Other
650 _ 7 |a Sample size
|2 Other
650 _ 7 |a ß-amyloid
|2 Other
650 _ 7 |a Biomarkers
|2 NLM Chemicals
650 _ 7 |a Amyloid beta-Peptides
|2 NLM Chemicals
650 _ 7 |a tau Proteins
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Alzheimer Disease: genetics
|2 MeSH
650 _ 2 |a Alzheimer Disease: cerebrospinal fluid
|2 MeSH
650 _ 2 |a Alzheimer Disease: diagnosis
|2 MeSH
650 _ 2 |a Alzheimer Disease: diagnostic imaging
|2 MeSH
650 _ 2 |a Alzheimer Disease: pathology
|2 MeSH
650 _ 2 |a Biomarkers: cerebrospinal fluid
|2 MeSH
650 _ 2 |a Amyloid beta-Peptides: cerebrospinal fluid
|2 MeSH
650 _ 2 |a Sample Size
|2 MeSH
650 _ 2 |a tau Proteins: cerebrospinal fluid
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Clinical Trials as Topic
|2 MeSH
650 _ 2 |a Outcome Assessment, Health Care
|2 MeSH
650 _ 2 |a Magnetic Resonance Imaging
|2 MeSH
650 _ 2 |a Positron-Emission Tomography
|2 MeSH
650 _ 2 |a Brain: pathology
|2 MeSH
650 _ 2 |a Brain: diagnostic imaging
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
700 1 _ |a Morgan, Katy E
|b 1
700 1 _ |a O'Connor, Antoinette
|b 2
700 1 _ |a Veale, Thomas D
|b 3
700 1 _ |a Malone, Ian B
|b 4
700 1 _ |a Poole, Teresa
|b 5
700 1 _ |a Benzinger, Tammie Ls
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700 1 _ |a Gordon, Brian A
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700 1 _ |a Ibanez, Laura
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700 1 _ |a Li, Yan
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700 1 _ |a Llibre-Guerra, Jorge J
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700 1 _ |a McDade, Eric
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700 1 _ |a Wang, Guoqiao
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700 1 _ |a Chhatwal, Jasmeer P
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700 1 _ |a Day, Gregory S
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700 1 _ |a Huey, Edward
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700 1 _ |a Jucker, Mathias
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700 1 _ |a Levin, Johannes
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700 1 _ |a Niimi, Yoshiki
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700 1 _ |a Noble, James M
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700 1 _ |a Roh, Jee Hoon
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700 1 _ |a Sánchez-Valle, Racquel
|b 21
700 1 _ |a Schofield, Peter R
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700 1 _ |a Bateman, Randall J
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700 1 _ |a Frost, Chris
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700 1 _ |a Fox, Nick C
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700 1 _ |a Network, Dominantly Inherited Alzheimer
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773 _ _ |a 10.1016/j.tjpad.2025.100133
|g Vol. 12, no. 6, p. 100133 -
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