Cognitive markers of preclinical and prodromal Alzheimer's disease in Down syndrome

Carla M Startin; Sarah Hamburg; Rosalyn Hithersay; Tamara Al-Janabi; Kin Y Mok; John Hardy; LonDownS Consortium; Andre Strydom

doi:10.1016/j.jalz.2018.08.009

Cognitive markers of preclinical and prodromal Alzheimer's disease in Down syndrome

Alzheimers Dement. 2019 Feb;15(2):245-257. doi: 10.1016/j.jalz.2018.08.009. Epub 2018 Nov 28.

Authors

Carla M Startin¹, Sarah Hamburg², Rosalyn Hithersay², Tamara Al-Janabi³, Kin Y Mok⁴, John Hardy⁵; LonDownS Consortium; Andre Strydom²

Collaborators

LonDownS Consortium:
Andre Strydom, Elizabeth Fisher, Dean Nizetic, John Hardy, Victor Tybulewicz, Annette Karmiloff-Smith, Nidhi Aggarwal, Amy Davies, Lucy Fodor-Wynne, Bryony Lowe, Erin Rodger, Laura Checkley, Paul Gallagher, Bernice Knight, Anne-Marije Prins, Rory Sheehan, David Zhang

Affiliations

¹ Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Division of Psychiatry, University College London, London, UK; The LonDownS Consortium, London, UK. Electronic address: carla.startin.09@ucl.ac.uk.
² Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Division of Psychiatry, University College London, London, UK; The LonDownS Consortium, London, UK.
³ Division of Psychiatry, University College London, London, UK; The LonDownS Consortium, London, UK.
⁴ The LonDownS Consortium, London, UK; Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK; Division of Life Science, Hong Kong University of Science and Technology, Hong Kong SAR, People's Republic of China.
⁵ The LonDownS Consortium, London, UK; Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK; Reta Lila Weston Institute, Institute of Neurology, University College London, London, UK.

Abstract

Introduction: Down syndrome (DS) is associated with an almost universal development of Alzheimer's disease. Individuals with DS are therefore an important population for randomized controlled trials to prevent or delay cognitive decline, though it is essential to understand the time course of early cognitive changes.

Methods: We conducted the largest cognitive study to date with 312 adults with DS to assess age-related and Alzheimer's disease-related cognitive changes during progression from preclinical to prodromal dementia, and prodromal to clinical dementia.

Results: Changes in memory and attention measures were most sensitive to early decline. Resulting sample size calculations for randomized controlled trials to detect significant treatment effects to delay decline were modest.

Discussion: Our findings address uncertainties around the development of randomized controlled trials to delay cognitive decline in DS. Such trials are essential to reduce the high burden of dementia in people with DS and could serve as proof-of-principle trials for some drug targets.

Keywords: Alzheimer's disease; Cognitive decline; Dementia; Down syndrome; Preclinical; Prodromal; Randomized controlled trials.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Alzheimer Disease / diagnosis*
Alzheimer Disease / physiopathology*
Biomarkers*
Cognitive Dysfunction / diagnosis*
Disease Progression
Down Syndrome / genetics
Down Syndrome / physiopathology*
Female
Humans
Middle Aged
Neuropsychological Tests / statistics & numerical data
Prodromal Symptoms*
Young Adult

Substances

Biomarkers

Abstract

Publication types

MeSH terms

Substances

Grants and funding