Markers of early changes in cognition across cohorts of adults with down syndrome at risk of alzheimer’s disease

Andrew J. Aschenbrenner; R. Asaad Baksh; Bessy Benejam; Jessica A. Beresford-Webb; Antonia Coppus; Juan Fortea; Benjamin L. Handen; Sigan Hartley; Elizabeth Head; Judith Jaeger; Johannes Levin; Sandra V. Loosli; Anne Sophie Rebillat; Silvia Sacco; Frederick A. Schmitt; Kate E. Thurlow; Shahid Zaman; Jason Hassenstab; Andre Strydom

doi:10.1002/dad2.12184

Markers of early changes in cognition across cohorts of adults with down syndrome at risk of alzheimer’s disease

Andrew J. Aschenbrenner, R. Asaad Baksh, Bessy Benejam, Jessica A. Beresford-Webb, Antonia Coppus, Juan Fortea, Benjamin L. Handen, Sigan Hartley, Elizabeth Head, Judith Jaeger, Johannes Levin, Sandra V. Loosli, Anne Sophie Rebillat, Silvia Sacco, Frederick A. Schmitt, Kate E. Thurlow, Shahid Zaman, Jason Hassenstab, Andre Strydom

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

6 Scopus citations

Abstract

Introduction: Down syndrome (DS), a genetic variant of early onset Alzheimer’s disease (AD), lacks a suitable outcome measure for prevention trials targeting predementia stages. Methods: We used cognitive test data collected in several longitudinal aging studies internationally from 312 participants with DS without dementia to identify composites that were sensitive to change over time.We then conducted additional analyses to provide support for the utility of the composites. The composites were presented to an expert panel to determine the most optimal cognitive battery based on predetermined criteria. Results: There were common cognitive domains across site composites, which were sensitive to early decline. The final composite consisted ofmemory, language/executive functioning, selective attention, orientation, and praxis tests. Discussion:We have identified a composite that is sensitive to early decline and thus may have utility as an outcome measure in trials to prevent or delay symptoms of AD in DS.

Original language	English
Article number	e12184
Journal	Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Volume	13
Issue number	1
DOIs	https://doi.org/10.1002/dad2.12184
State	Published - 2021

Bibliographical note

Funding Information:
The authors acknowledge all the participants in this study for their time. We would also like to thank Katherine Van Pelt and Allison Caban-Holt from the Kentucky site; Sarah Hamburg, Rosalyn Hither-say, and Carla Startin from the London site; and Laura Videla from Barcelona for their work on initial data collection. We would like to thank Rosalyn Hithersay and Sarah Pape from the London site, Isabel Clare from the Cambridge site, and Anna Esbensen from the Thomas Center for Down Syndrome at Cincinnati Children’s Hospital for participating in the consensus discussion. This work was funded by grants from the LuMind IDSC Foundation, the Jérôme Lejeune Foundation, the Wellcome Trust Strategic Award (grant number: 098330/Z/12/Z), the Medical Research Council (MRC MR/S011277/1; MR/S005145/1; MR/R024901/1), the Verum Foundation, the Deutsche Forschungs-gemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198), the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development (NIH/NICHD R01HD064993), the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC-1215-20014), and NIH funding was also received to support the study (R01AG031110 and U01AG051406). The study funders and sponsors had no role in study design, data collection, data analysis, data interpretation, writing of the report, or the decision to submit for publication. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

Funding Information:
the LuMind IDSC Foundation; the Jérôme Lejeune Foundation; the Wellcome Trust Strategic Award, Grant/Award Number: 098330/Z/12/Z; the Medical Research Council, Grant/Award Numbers: MRC MR/S011277/1, MR/S005145/1, MR/R024901/1; the Verum Foundation; the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) Munich Cluster for Systems Neurology, Grant/Award Number: ID 390857198; the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development NIH/NICHD, Grant/Award Number: R01HD064993; the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, Grant/Award Number: BRC-1215-20014; National Institutes of Health, Grant/Award Numbers: R01AG031110, U01AG051406

Funding Information:
Dr. Juan Fortea is on the advisory board for AC Immune and Lündbeck and is a consultant for Novartis. Dr. Juan Fortea has received compensation for consultancies to Novartis, Lündbeck, and AC Immune. Dr. Benjamin L. Handen received research funding from Roche. Dr. Andre Strydom received funding from AC Immune and is an advisor to ProMIS neurosciences. All other authors declare no conflicts of interest.

Funding Information:
This work was funded by grants from the LuMind IDSC Foundation, the J?r?me Lejeune Foundation, the Wellcome Trust Strategic Award (grant number: 098330/Z/12/Z).

Publisher Copyright:
© 2021 The Authors.

Keywords

Alzheimer’s disease
Clinical trial outcome
Composite measure
Down syndrome
Early cognitive decline

ASJC Scopus subject areas

Clinical Neurology
Psychiatry and Mental health

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1002/dad2.12184

Cite this

Aschenbrenner, A. J., Asaad Baksh, R., Benejam, B., Beresford-Webb, J. A., Coppus, A., Fortea, J., Handen, B. L., Hartley, S., Head, E., Jaeger, J., Levin, J., Loosli, S. V., Rebillat, A. S., Sacco, S., Schmitt, F. A., Thurlow, K. E., Zaman, S., Hassenstab, J., & Strydom, A. (2021). Markers of early changes in cognition across cohorts of adults with down syndrome at risk of alzheimer’s disease. Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, 13(1), [e12184]. https://doi.org/10.1002/dad2.12184

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title = "Markers of early changes in cognition across cohorts of adults with down syndrome at risk of alzheimer{\textquoteright}s disease",

abstract = "Introduction: Down syndrome (DS), a genetic variant of early onset Alzheimer{\textquoteright}s disease (AD), lacks a suitable outcome measure for prevention trials targeting predementia stages. Methods: We used cognitive test data collected in several longitudinal aging studies internationally from 312 participants with DS without dementia to identify composites that were sensitive to change over time.We then conducted additional analyses to provide support for the utility of the composites. The composites were presented to an expert panel to determine the most optimal cognitive battery based on predetermined criteria. Results: There were common cognitive domains across site composites, which were sensitive to early decline. The final composite consisted ofmemory, language/executive functioning, selective attention, orientation, and praxis tests. Discussion:We have identified a composite that is sensitive to early decline and thus may have utility as an outcome measure in trials to prevent or delay symptoms of AD in DS.",

keywords = "Alzheimer{\textquoteright}s disease, Clinical trial outcome, Composite measure, Down syndrome, Early cognitive decline",

author = "Aschenbrenner, {Andrew J.} and {Asaad Baksh}, R. and Bessy Benejam and Beresford-Webb, {Jessica A.} and Antonia Coppus and Juan Fortea and Handen, {Benjamin L.} and Sigan Hartley and Elizabeth Head and Judith Jaeger and Johannes Levin and Loosli, {Sandra V.} and Rebillat, {Anne Sophie} and Silvia Sacco and Schmitt, {Frederick A.} and Thurlow, {Kate E.} and Shahid Zaman and Jason Hassenstab and Andre Strydom",

note = "Funding Information: The authors acknowledge all the participants in this study for their time. We would also like to thank Katherine Van Pelt and Allison Caban-Holt from the Kentucky site; Sarah Hamburg, Rosalyn Hither-say, and Carla Startin from the London site; and Laura Videla from Barcelona for their work on initial data collection. We would like to thank Rosalyn Hithersay and Sarah Pape from the London site, Isabel Clare from the Cambridge site, and Anna Esbensen from the Thomas Center for Down Syndrome at Cincinnati Children{\textquoteright}s Hospital for participating in the consensus discussion. This work was funded by grants from the LuMind IDSC Foundation, the J{\'e}r{\^o}me Lejeune Foundation, the Wellcome Trust Strategic Award (grant number: 098330/Z/12/Z), the Medical Research Council (MRC MR/S011277/1; MR/S005145/1; MR/R024901/1), the Verum Foundation, the Deutsche Forschungs-gemeinschaft (DFG, German Research Foundation) under Germany{\textquoteright}s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198), the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development (NIH/NICHD R01HD064993), the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC-1215-20014), and NIH funding was also received to support the study (R01AG031110 and U01AG051406). The study funders and sponsors had no role in study design, data collection, data analysis, data interpretation, writing of the report, or the decision to submit for publication. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Funding Information: the LuMind IDSC Foundation; the J{\'e}r{\^o}me Lejeune Foundation; the Wellcome Trust Strategic Award, Grant/Award Number: 098330/Z/12/Z; the Medical Research Council, Grant/Award Numbers: MRC MR/S011277/1, MR/S005145/1, MR/R024901/1; the Verum Foundation; the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) Munich Cluster for Systems Neurology, Grant/Award Number: ID 390857198; the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development NIH/NICHD, Grant/Award Number: R01HD064993; the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, Grant/Award Number: BRC-1215-20014; National Institutes of Health, Grant/Award Numbers: R01AG031110, U01AG051406 Funding Information: Dr. Juan Fortea is on the advisory board for AC Immune and L{\"u}ndbeck and is a consultant for Novartis. Dr. Juan Fortea has received compensation for consultancies to Novartis, L{\"u}ndbeck, and AC Immune. Dr. Benjamin L. Handen received research funding from Roche. Dr. Andre Strydom received funding from AC Immune and is an advisor to ProMIS neurosciences. All other authors declare no conflicts of interest. Funding Information: This work was funded by grants from the LuMind IDSC Foundation, the J?r?me Lejeune Foundation, the Wellcome Trust Strategic Award (grant number: 098330/Z/12/Z). Publisher Copyright: {\textcopyright} 2021 The Authors.",

year = "2021",

doi = "10.1002/dad2.12184",

language = "English",

volume = "13",

number = "1",

}

Aschenbrenner, AJ, Asaad Baksh, R, Benejam, B, Beresford-Webb, JA, Coppus, A, Fortea, J, Handen, BL, Hartley, S, Head, E, Jaeger, J, Levin, J, Loosli, SV, Rebillat, AS, Sacco, S, Schmitt, FA, Thurlow, KE, Zaman, S, Hassenstab, J & Strydom, A 2021, 'Markers of early changes in cognition across cohorts of adults with down syndrome at risk of alzheimer’s disease', Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, vol. 13, no. 1, e12184. https://doi.org/10.1002/dad2.12184

TY - JOUR

T1 - Markers of early changes in cognition across cohorts of adults with down syndrome at risk of alzheimer’s disease

AU - Aschenbrenner, Andrew J.

AU - Asaad Baksh, R.

AU - Benejam, Bessy

AU - Beresford-Webb, Jessica A.

AU - Coppus, Antonia

AU - Fortea, Juan

AU - Handen, Benjamin L.

AU - Hartley, Sigan

AU - Head, Elizabeth

AU - Jaeger, Judith

AU - Levin, Johannes

AU - Loosli, Sandra V.

AU - Rebillat, Anne Sophie

AU - Sacco, Silvia

AU - Schmitt, Frederick A.

AU - Thurlow, Kate E.

AU - Zaman, Shahid

AU - Hassenstab, Jason

AU - Strydom, Andre

N1 - Funding Information: The authors acknowledge all the participants in this study for their time. We would also like to thank Katherine Van Pelt and Allison Caban-Holt from the Kentucky site; Sarah Hamburg, Rosalyn Hither-say, and Carla Startin from the London site; and Laura Videla from Barcelona for their work on initial data collection. We would like to thank Rosalyn Hithersay and Sarah Pape from the London site, Isabel Clare from the Cambridge site, and Anna Esbensen from the Thomas Center for Down Syndrome at Cincinnati Children’s Hospital for participating in the consensus discussion. This work was funded by grants from the LuMind IDSC Foundation, the Jérôme Lejeune Foundation, the Wellcome Trust Strategic Award (grant number: 098330/Z/12/Z), the Medical Research Council (MRC MR/S011277/1; MR/S005145/1; MR/R024901/1), the Verum Foundation, the Deutsche Forschungs-gemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198), the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development (NIH/NICHD R01HD064993), the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC-1215-20014), and NIH funding was also received to support the study (R01AG031110 and U01AG051406). The study funders and sponsors had no role in study design, data collection, data analysis, data interpretation, writing of the report, or the decision to submit for publication. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Funding Information: the LuMind IDSC Foundation; the Jérôme Lejeune Foundation; the Wellcome Trust Strategic Award, Grant/Award Number: 098330/Z/12/Z; the Medical Research Council, Grant/Award Numbers: MRC MR/S011277/1, MR/S005145/1, MR/R024901/1; the Verum Foundation; the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) Munich Cluster for Systems Neurology, Grant/Award Number: ID 390857198; the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development NIH/NICHD, Grant/Award Number: R01HD064993; the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, Grant/Award Number: BRC-1215-20014; National Institutes of Health, Grant/Award Numbers: R01AG031110, U01AG051406 Funding Information: Dr. Juan Fortea is on the advisory board for AC Immune and Lündbeck and is a consultant for Novartis. Dr. Juan Fortea has received compensation for consultancies to Novartis, Lündbeck, and AC Immune. Dr. Benjamin L. Handen received research funding from Roche. Dr. Andre Strydom received funding from AC Immune and is an advisor to ProMIS neurosciences. All other authors declare no conflicts of interest. Funding Information: This work was funded by grants from the LuMind IDSC Foundation, the J?r?me Lejeune Foundation, the Wellcome Trust Strategic Award (grant number: 098330/Z/12/Z). Publisher Copyright: © 2021 The Authors.

PY - 2021

Y1 - 2021

N2 - Introduction: Down syndrome (DS), a genetic variant of early onset Alzheimer’s disease (AD), lacks a suitable outcome measure for prevention trials targeting predementia stages. Methods: We used cognitive test data collected in several longitudinal aging studies internationally from 312 participants with DS without dementia to identify composites that were sensitive to change over time.We then conducted additional analyses to provide support for the utility of the composites. The composites were presented to an expert panel to determine the most optimal cognitive battery based on predetermined criteria. Results: There were common cognitive domains across site composites, which were sensitive to early decline. The final composite consisted ofmemory, language/executive functioning, selective attention, orientation, and praxis tests. Discussion:We have identified a composite that is sensitive to early decline and thus may have utility as an outcome measure in trials to prevent or delay symptoms of AD in DS.

AB - Introduction: Down syndrome (DS), a genetic variant of early onset Alzheimer’s disease (AD), lacks a suitable outcome measure for prevention trials targeting predementia stages. Methods: We used cognitive test data collected in several longitudinal aging studies internationally from 312 participants with DS without dementia to identify composites that were sensitive to change over time.We then conducted additional analyses to provide support for the utility of the composites. The composites were presented to an expert panel to determine the most optimal cognitive battery based on predetermined criteria. Results: There were common cognitive domains across site composites, which were sensitive to early decline. The final composite consisted ofmemory, language/executive functioning, selective attention, orientation, and praxis tests. Discussion:We have identified a composite that is sensitive to early decline and thus may have utility as an outcome measure in trials to prevent or delay symptoms of AD in DS.

KW - Alzheimer’s disease

KW - Clinical trial outcome

KW - Composite measure

KW - Down syndrome

KW - Early cognitive decline

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DO - 10.1002/dad2.12184

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Markers of early changes in cognition across cohorts of adults with down syndrome at risk of alzheimer’s disease

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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