Optimal age and outcome measures for Alzheimer's disease prevention trials in people with Down syndrome

Rosalyn Hithersay; R Asaad Baksh; Carla Startin; Peter A. Wijeratne; Sarah Hamburg; Ben Carter; André Strydom

doi:10.1002/alz.12222

Optimal age and outcome measures for Alzheimer's disease prevention trials in people with Down syndrome

Rosalyn Hithersay, R Asaad Baksh, Carla Startin, Peter A. Wijeratne, Sarah Hamburg, Ben Carter, André Strydom

Research output: Contribution to journal › Article › peer-review

Abstract

Introduction: People with Down syndrome (DS) typically develop Alzheimer's disease (AD) neuropathology before age 40, but a lack of outcome measures and longitudinal data have impeded their inclusion in randomized controlled trials (RCTs).
Methods: Cohort study. Event‐based and dose‐response Emax models were fitted to longitudinal cognitive data, to stage AD and determine the earliest ages of decline. Results informed sample size estimations for hypothetical RCTs of disease‐modifying treatments that reduced decline by 35% or 75%.
Results: Seventy‐five percent of participants progressed or remained stable in the AD staging model; effect sizes varied by age group and tests. Varied treatment effects could be detected with 50‐200 people per arm when using sensitive cognitive outcome measures and targeting recruitment to ages 36 to 45 years.
Discussion: Efficient RCTs of AD preventative treatments can be conducted in the DS population using sensitive outcome measures to monitor early decline. Dose‐response models could help tailor future RCTs.

Original language	English
Journal	Alzheimers and Dementia
DOIs	https://doi.org/10.1002/alz.12222
Publication status	Published - 23 Nov 2020

Access to Document

10.1002/alz.12222Licence: CC BY

https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.12222Licence: CC BY

Cite this

@article{549aa9baf63a4b4fad1478a5492d8329,

title = "Optimal age and outcome measures for Alzheimer's disease prevention trials in people with Down syndrome",

abstract = "Introduction: People with Down syndrome (DS) typically develop Alzheimer's disease (AD) neuropathology before age 40, but a lack of outcome measures and longitudinal data have impeded their inclusion in randomized controlled trials (RCTs).Methods: Cohort study. Event‐based and dose‐response Emax models were fitted to longitudinal cognitive data, to stage AD and determine the earliest ages of decline. Results informed sample size estimations for hypothetical RCTs of disease‐modifying treatments that reduced decline by 35% or 75%.Results: Seventy‐five percent of participants progressed or remained stable in the AD staging model; effect sizes varied by age group and tests. Varied treatment effects could be detected with 50‐200 people per arm when using sensitive cognitive outcome measures and targeting recruitment to ages 36 to 45 years.Discussion: Efficient RCTs of AD preventative treatments can be conducted in the DS population using sensitive outcome measures to monitor early decline. Dose‐response models could help tailor future RCTs.",

author = "Rosalyn Hithersay and Baksh, {R Asaad} and Carla Startin and Wijeratne, {Peter A.} and Sarah Hamburg and Ben Carter and Andr{\'e} Strydom",

year = "2020",

month = nov,

day = "23",

doi = "10.1002/alz.12222",

language = "English",

journal = "Alzheimers and Dementia",

issn = "1552-5260",

publisher = "Elsevier",

}

TY - JOUR

T1 - Optimal age and outcome measures for Alzheimer's disease prevention trials in people with Down syndrome

AU - Hithersay, Rosalyn

AU - Baksh, R Asaad

AU - Startin, Carla

AU - Wijeratne, Peter A.

AU - Hamburg, Sarah

AU - Carter, Ben

AU - Strydom, André

PY - 2020/11/23

Y1 - 2020/11/23

N2 - Introduction: People with Down syndrome (DS) typically develop Alzheimer's disease (AD) neuropathology before age 40, but a lack of outcome measures and longitudinal data have impeded their inclusion in randomized controlled trials (RCTs).Methods: Cohort study. Event‐based and dose‐response Emax models were fitted to longitudinal cognitive data, to stage AD and determine the earliest ages of decline. Results informed sample size estimations for hypothetical RCTs of disease‐modifying treatments that reduced decline by 35% or 75%.Results: Seventy‐five percent of participants progressed or remained stable in the AD staging model; effect sizes varied by age group and tests. Varied treatment effects could be detected with 50‐200 people per arm when using sensitive cognitive outcome measures and targeting recruitment to ages 36 to 45 years.Discussion: Efficient RCTs of AD preventative treatments can be conducted in the DS population using sensitive outcome measures to monitor early decline. Dose‐response models could help tailor future RCTs.

AB - Introduction: People with Down syndrome (DS) typically develop Alzheimer's disease (AD) neuropathology before age 40, but a lack of outcome measures and longitudinal data have impeded their inclusion in randomized controlled trials (RCTs).Methods: Cohort study. Event‐based and dose‐response Emax models were fitted to longitudinal cognitive data, to stage AD and determine the earliest ages of decline. Results informed sample size estimations for hypothetical RCTs of disease‐modifying treatments that reduced decline by 35% or 75%.Results: Seventy‐five percent of participants progressed or remained stable in the AD staging model; effect sizes varied by age group and tests. Varied treatment effects could be detected with 50‐200 people per arm when using sensitive cognitive outcome measures and targeting recruitment to ages 36 to 45 years.Discussion: Efficient RCTs of AD preventative treatments can be conducted in the DS population using sensitive outcome measures to monitor early decline. Dose‐response models could help tailor future RCTs.

U2 - 10.1002/alz.12222

DO - 10.1002/alz.12222

M3 - Article

SN - 1552-5260

JO - Alzheimers and Dementia

JF - Alzheimers and Dementia

ER -