Resistance and resilience to Alzheimer's disease in Down syndrome

Rory Boyle; Elouise A Koops; Beau Ances; Elizabeth J Andrews; Eider M Arenaza-Urquijo; Alexandre Benjanin; Adam M Brickman; Rachel F Buckley; Giulia S Clas; Emmet Costello; Gillian T Coughlan; Alexander C Conley; Feng Deng; Daniele de Paula Faria; Natalie Edwards; Lisi Flores-Aguilar; Juan Fortea; Ladan Ghazi Saidi; Elizabeth Head; Christy L Hom; Katherine Koenig; Patrick Lao; Imre Lengyel; Yi-Ju Li; Samantha Loi; David Loughrey; Eimear McGlinchey; Paul Newhouse; Lucía Pertierra; Prokopis C Prokopiou; Qing Qi; Elisa de Paula França Resende; Jason Russell; Catherine E Scanlon; Christoph Schneider; Stephanie A Schultz; Mabel Seto; Sophia Shaka; Anja Soldan; Lídia Vaqué Alcázar; Yihe Weng; Jo Ellen Wilson; Shahid H Zaman; Sára E Zsadányi; Sigan Hartley

doi:10.1002/alz.70151

Resistance and resilience to Alzheimer's disease in Down syndrome

Rory Boyle
, Elouise A Koops
, Beau Ances
, Elizabeth J Andrews
, Eider M Arenaza-Urquijo
, Alexandre Benjanin
, Adam M Brickman
, Rachel F Buckley
, Giulia S Clas
, Emmet Costello
, Gillian T Coughlan
, Alexander C Conley
, Feng Deng
, Daniele de Paula Faria
, Natalie Edwards
, Lisi Flores-Aguilar
, Juan Fortea
, Ladan Ghazi Saidi
, Elizabeth Head
, Christy L Hom

Katherine Koenig, Patrick Lao, Imre Lengyel, Yi-Ju Li, Samantha Loi, David Loughrey, Eimear McGlinchey, Paul Newhouse, Lucía Pertierra, Prokopis C Prokopiou, Qing Qi, Elisa de Paula França Resende, Jason Russell, Catherine E Scanlon, Christoph Schneider, Stephanie A Schultz, Mabel Seto, Sophia Shaka, Anja Soldan, Lídia Vaqué Alcázar, Yihe Weng, Jo Ellen Wilson, Shahid H Zaman, Sára E Zsadányi, Sigan Hartley

School of Medicine, Dentistry and Biomedical Sciences

Research output: Contribution to journal › Review article › peer-review

6 Citations (Scopus)

46 Downloads (Pure)

Abstract

Due to the high prevalence of Alzheimer's disease (AD) in adults with Down syndrome (DS), trisomy 21 is now considered a genetic form of AD (DSAD). A better understanding of factors that can prevent or delay AD is vital to improve outcomes for adults with DS. In this narrative review, we apply AD and cognitive aging research frameworks to study resistance and resilience in DSAD. Given the variability in the timing of pathology and symptoms, we discuss the evidence supporting the role of genetic, biological, socio-behavioral, lifestyle, and environmental factors in resistance and resilience to DSAD. We also consider how co-occurring health conditions in DS may influence resistance and resilience, and how methods from AD research can be applied to DSAD. Ultimately, this framework aims to guide future research and translate findings into clinical interventions to improve outcomes in DSAD. Highlights Definitions of resistance and resilience in the genetic form of Alzheimer's disease (DSAD) are proposed for guiding the field. Variability in the timing of AD pathology and symptoms suggests the potential for resistance and resilience mechanisms in DSAD. Genetic, biological, socio-behavioral, lifestyle, and environmental factors have the potential to build resistance or resilience in DSAD. Future research will require longitudinal and experimental designs, life course approaches, and large cohort studies.

Original language	English
Article number	e70151
Journal	Alzheimer's & Dementia: The Journal of the Alzheimer's Association
Volume	21
Issue number	4
DOIs	https://doi.org/10.1002/alz.70151
Publication status	Published - 28 Apr 2025

Bibliographical note

Keywords

Humans
Down Syndrome/complications
Alzheimer Disease/genetics
Resilience, Psychological

Access to Document

10.1002/alz.70151Licence: CC BY

Resistance and resilience to Alzheimer's disease in Down syndrome
Copyright 2025 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 552 KBLicence: CC BY

Cite this

Boyle, R., Koops, E. A., Ances, B., Andrews, E. J., Arenaza-Urquijo, E. M., Benjanin, A., Brickman, A. M., Buckley, R. F., Clas, G. S., Costello, E., Coughlan, G. T., Conley, A. C., Deng, F., de Paula Faria, D., Edwards, N., Flores-Aguilar, L., Fortea, J., Ghazi Saidi, L., Head, E., ... Hartley, S. (2025). Resistance and resilience to Alzheimer's disease in Down syndrome. Alzheimer's & Dementia: The Journal of the Alzheimer's Association, 21(4), Article e70151. https://doi.org/10.1002/alz.70151

@article{b37b167d9cb649dcbb0107c88d89c4cd,

title = "Resistance and resilience to Alzheimer's disease in Down syndrome",

abstract = "Due to the high prevalence of Alzheimer's disease (AD) in adults with Down syndrome (DS), trisomy 21 is now considered a genetic form of AD (DSAD). A better understanding of factors that can prevent or delay AD is vital to improve outcomes for adults with DS. In this narrative review, we apply AD and cognitive aging research frameworks to study resistance and resilience in DSAD. Given the variability in the timing of pathology and symptoms, we discuss the evidence supporting the role of genetic, biological, socio-behavioral, lifestyle, and environmental factors in resistance and resilience to DSAD. We also consider how co-occurring health conditions in DS may influence resistance and resilience, and how methods from AD research can be applied to DSAD. Ultimately, this framework aims to guide future research and translate findings into clinical interventions to improve outcomes in DSAD. Highlights Definitions of resistance and resilience in the genetic form of Alzheimer's disease (DSAD) are proposed for guiding the field. Variability in the timing of AD pathology and symptoms suggests the potential for resistance and resilience mechanisms in DSAD. Genetic, biological, socio-behavioral, lifestyle, and environmental factors have the potential to build resistance or resilience in DSAD. Future research will require longitudinal and experimental designs, life course approaches, and large cohort studies.",

keywords = "Humans, Down Syndrome/complications, Alzheimer Disease/genetics, Resilience, Psychological",

author = "Rory Boyle and Koops, \{Elouise A\} and Beau Ances and Andrews, \{Elizabeth J\} and Arenaza-Urquijo, \{Eider M\} and Alexandre Benjanin and Brickman, \{Adam M\} and Buckley, \{Rachel F\} and Clas, \{Giulia S\} and Emmet Costello and Coughlan, \{Gillian T\} and Conley, \{Alexander C\} and Feng Deng and \{de Paula Faria\}, Daniele and Natalie Edwards and Lisi Flores-Aguilar and Juan Fortea and \{Ghazi Saidi\}, Ladan and Elizabeth Head and Hom, \{Christy L\} and Katherine Koenig and Patrick Lao and Imre Lengyel and Yi-Ju Li and Samantha Loi and David Loughrey and Eimear McGlinchey and Paul Newhouse and Luc{\'i}a Pertierra and Prokopiou, \{Prokopis C\} and Qing Qi and \{de Paula Fran{\c c}a Resende\}, Elisa and Jason Russell and Scanlon, \{Catherine E\} and Christoph Schneider and Schultz, \{Stephanie A\} and Mabel Seto and Sophia Shaka and Anja Soldan and \{Vaqu{\'e} Alc{\'a}zar\}, L{\'i}dia and Yihe Weng and Wilson, \{Jo Ellen\} and Zaman, \{Shahid H\} and Zsad{\'a}nyi, \{S{\'a}ra E\} and Sigan Hartley",

note = "{\textcopyright} 2025 The Author(s). Alzheimer's \& Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2025",

month = apr,

day = "28",

doi = "10.1002/alz.70151",

language = "English",

volume = "21",

journal = "Alzheimer's \& Dementia: The Journal of the Alzheimer's Association",

issn = "1552-5260",

publisher = "John Wiley \& Sons Inc.",

number = "4",

}

Boyle, R, Koops, EA, Ances, B, Andrews, EJ, Arenaza-Urquijo, EM, Benjanin, A, Brickman, AM, Buckley, RF, Clas, GS, Costello, E, Coughlan, GT, Conley, AC, Deng, F, de Paula Faria, D, Edwards, N, Flores-Aguilar, L, Fortea, J, Ghazi Saidi, L, Head, E, Hom, CL, Koenig, K, Lao, P, Lengyel, I, Li, Y-J, Loi, S, Loughrey, D, McGlinchey, E, Newhouse, P, Pertierra, L, Prokopiou, PC, Qi, Q, de Paula França Resende, E, Russell, J, Scanlon, CE, Schneider, C, Schultz, SA, Seto, M, Shaka, S, Soldan, A, Vaqué Alcázar, L, Weng, Y, Wilson, JE, Zaman, SH, Zsadányi, SE & Hartley, S 2025, 'Resistance and resilience to Alzheimer's disease in Down syndrome', Alzheimer's & Dementia: The Journal of the Alzheimer's Association, vol. 21, no. 4, e70151. https://doi.org/10.1002/alz.70151

TY - JOUR

T1 - Resistance and resilience to Alzheimer's disease in Down syndrome

AU - Boyle, Rory

AU - Koops, Elouise A

AU - Ances, Beau

AU - Andrews, Elizabeth J

AU - Arenaza-Urquijo, Eider M

AU - Benjanin, Alexandre

AU - Brickman, Adam M

AU - Buckley, Rachel F

AU - Clas, Giulia S

AU - Costello, Emmet

AU - Coughlan, Gillian T

AU - Conley, Alexander C

AU - Deng, Feng

AU - de Paula Faria, Daniele

AU - Edwards, Natalie

AU - Flores-Aguilar, Lisi

AU - Fortea, Juan

AU - Ghazi Saidi, Ladan

AU - Head, Elizabeth

AU - Hom, Christy L

AU - Koenig, Katherine

AU - Lao, Patrick

AU - Lengyel, Imre

AU - Li, Yi-Ju

AU - Loi, Samantha

AU - Loughrey, David

AU - McGlinchey, Eimear

AU - Newhouse, Paul

AU - Pertierra, Lucía

AU - Prokopiou, Prokopis C

AU - Qi, Qing

AU - de Paula França Resende, Elisa

AU - Russell, Jason

AU - Scanlon, Catherine E

AU - Schneider, Christoph

AU - Schultz, Stephanie A

AU - Seto, Mabel

AU - Shaka, Sophia

AU - Soldan, Anja

AU - Vaqué Alcázar, Lídia

AU - Weng, Yihe

AU - Wilson, Jo Ellen

AU - Zaman, Shahid H

AU - Zsadányi, Sára E

AU - Hartley, Sigan

PY - 2025/4/28

Y1 - 2025/4/28

N2 - Due to the high prevalence of Alzheimer's disease (AD) in adults with Down syndrome (DS), trisomy 21 is now considered a genetic form of AD (DSAD). A better understanding of factors that can prevent or delay AD is vital to improve outcomes for adults with DS. In this narrative review, we apply AD and cognitive aging research frameworks to study resistance and resilience in DSAD. Given the variability in the timing of pathology and symptoms, we discuss the evidence supporting the role of genetic, biological, socio-behavioral, lifestyle, and environmental factors in resistance and resilience to DSAD. We also consider how co-occurring health conditions in DS may influence resistance and resilience, and how methods from AD research can be applied to DSAD. Ultimately, this framework aims to guide future research and translate findings into clinical interventions to improve outcomes in DSAD. Highlights Definitions of resistance and resilience in the genetic form of Alzheimer's disease (DSAD) are proposed for guiding the field. Variability in the timing of AD pathology and symptoms suggests the potential for resistance and resilience mechanisms in DSAD. Genetic, biological, socio-behavioral, lifestyle, and environmental factors have the potential to build resistance or resilience in DSAD. Future research will require longitudinal and experimental designs, life course approaches, and large cohort studies.

AB - Due to the high prevalence of Alzheimer's disease (AD) in adults with Down syndrome (DS), trisomy 21 is now considered a genetic form of AD (DSAD). A better understanding of factors that can prevent or delay AD is vital to improve outcomes for adults with DS. In this narrative review, we apply AD and cognitive aging research frameworks to study resistance and resilience in DSAD. Given the variability in the timing of pathology and symptoms, we discuss the evidence supporting the role of genetic, biological, socio-behavioral, lifestyle, and environmental factors in resistance and resilience to DSAD. We also consider how co-occurring health conditions in DS may influence resistance and resilience, and how methods from AD research can be applied to DSAD. Ultimately, this framework aims to guide future research and translate findings into clinical interventions to improve outcomes in DSAD. Highlights Definitions of resistance and resilience in the genetic form of Alzheimer's disease (DSAD) are proposed for guiding the field. Variability in the timing of AD pathology and symptoms suggests the potential for resistance and resilience mechanisms in DSAD. Genetic, biological, socio-behavioral, lifestyle, and environmental factors have the potential to build resistance or resilience in DSAD. Future research will require longitudinal and experimental designs, life course approaches, and large cohort studies.

KW - Humans

KW - Down Syndrome/complications

KW - Alzheimer Disease/genetics

KW - Resilience, Psychological

U2 - 10.1002/alz.70151

DO - 10.1002/alz.70151

M3 - Review article

C2 - 40289889

SN - 1552-5260

VL - 21

JO - Alzheimer's & Dementia: The Journal of the Alzheimer's Association

JF - Alzheimer's & Dementia: The Journal of the Alzheimer's Association

IS - 4

M1 - e70151

ER -

Resistance and resilience to Alzheimer's disease in Down syndrome

Abstract

Bibliographical note

Keywords

Access to Document

Fingerprint

Cite this