Different rates of cognitive decline in autosomal dominant and late-onset Alzheimer disease

for the Dominantly Inherited Alzheimer's Network

doi:10.1002/alz.12505

Different rates of cognitive decline in autosomal dominant and late-onset Alzheimer disease

for the Dominantly Inherited Alzheimer's Network

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

3 Scopus citations

Abstract

As prevention trials advance with autosomal dominant Alzheimer disease (ADAD) participants, understanding the similarities and differences between ADAD and “sporadic” late-onset AD (LOAD) is critical to determine generalizability of findings between these cohorts. Cognitive trajectories of ADAD mutation carriers (MCs) and autopsy-confirmed LOAD individuals were compared to address this question. Longitudinal rates of change on cognitive measures were compared in ADAD MCs (n = 310) and autopsy-confirmed LOAD participants (n = 163) before and after symptom onset (estimated/observed). LOAD participants declined more rapidly in the presymptomatic (preclinical) period and performed more poorly at symptom onset than ADAD participants on a cognitive composite. After symptom onset, however, the younger ADAD MCs declined more rapidly. The similar but not identical cognitive trajectories (declining but at different rates) for ADAD and LOAD suggest common AD pathologies but with some differences.

Original language	English
Pages (from-to)	1754-1764
Number of pages	11
Journal	Alzheimer's and Dementia
Volume	18
Issue number	10
DOIs	https://doi.org/10.1002/alz.12505
State	Published - Oct 2022

Keywords

Alzheimer disease
autosomal dominant Alzheimer disease
cognitive
comorbidities
late-onset Alzheimer disease

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10.1002/alz.12505

Cite this

@article{513ebc444c074635ba95686c4f92c1b0,

title = "Different rates of cognitive decline in autosomal dominant and late-onset Alzheimer disease",

abstract = "As prevention trials advance with autosomal dominant Alzheimer disease (ADAD) participants, understanding the similarities and differences between ADAD and “sporadic” late-onset AD (LOAD) is critical to determine generalizability of findings between these cohorts. Cognitive trajectories of ADAD mutation carriers (MCs) and autopsy-confirmed LOAD individuals were compared to address this question. Longitudinal rates of change on cognitive measures were compared in ADAD MCs (n = 310) and autopsy-confirmed LOAD participants (n = 163) before and after symptom onset (estimated/observed). LOAD participants declined more rapidly in the presymptomatic (preclinical) period and performed more poorly at symptom onset than ADAD participants on a cognitive composite. After symptom onset, however, the younger ADAD MCs declined more rapidly. The similar but not identical cognitive trajectories (declining but at different rates) for ADAD and LOAD suggest common AD pathologies but with some differences.",

keywords = "Alzheimer disease, autosomal dominant Alzheimer disease, cognitive, comorbidities, late-onset Alzheimer disease",

author = "{for the Dominantly Inherited Alzheimer's Network} and Buckles, {Virginia D.} and Chengjie Xiong and Bateman, {Randall J.} and Jason Hassenstab and Ricardo Allegri and Berman, {Sarah B.} and Chhatwal, {Jasmeer P.} and Adrian Danek and Fagan, {Anne M.} and Bernardino Ghetti and Alison Goate and Neill Graff-Radford and Mathias Jucker and Johannes Levin and Marcus, {Daniel S.} and Masters, {Colin L.} and Lena McCue and Eric McDade and Hiroshi Mori and Moulder, {Krista L.} and Noble, {James M.} and Katrina Paumier and Oliver Preische and Ringman, {John M.} and Fox, {Nick C.} and Stephen Salloway and Schofield, {Peter R.} and Ralph Martins and Jonathan V{\"o}glein and Morris, {John C.}",

note = "Funding Information: DIAN data collection and sharing for this project was supported by The Dominantly Inherited Alzheimer Network (DIAN, U19AG032438) funded by the National Institute on Aging (NIA), the German Center for Neurodegenerative Diseases (DZNE), Raul Carrea Institute for Neurological Research (FLENI). Partial support by the Research and Development Grants for Dementia from Japan Agency for Medical Research and Development, AMED and NIHR UCL/UCLH Biomedical Research Centre and the MRC Dementias Platform UK (MR/L023784/1 and MR/009076/1). This manuscript has been reviewed by DIAN Study investigators for scientific content and consistency of data interpretation with previous DIAN Study publications. We acknowledge the altruism of the participants and their families and contributions of the DIAN research and support staff at each of the participating sites for their contributions to this study. The NACC database is funded by NIA/NIH Grant U24 AG072122. NACC data are contributed by the NIA‐funded ADRCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P50 AG047266 (PI Todd Golde, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Thomas Wisniewski, MD), P30 AG013854 (PI Robert Vassar, PhD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P50 AG005131 (PI James Brewer, MD, PhD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG053760 (PI Henry Paulson, MD, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 and P30 AG066530 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P30 AG049638 (PI Suzanne Craft, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P50 AG033514 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John Morris, MD), P50 AG047270 (PI Stephen Strittmatter, MD, PhD). Funding Information: Drs. Allegri, Graff‐Radford, Masters, McCue, Mori, Paumier, Preische, Martins, and V{\"o}glein have nothing to disclose. Virginia D. Buckles received support as a consultant from Washington University in St. Louis. Chengjie Xiong has received grant support from NIH/NIA outside the submitted work. He also served on the University of Wisconsin Alzheimer's Disease Research Center External Advisory Committee. Randall J. Bateman has received support outside the submitted work from NIH/NIA, Avid Radiopharmaceuticals, Janssen, Eisai, Genentech, Eli Lilly & Co, Hoffman‐LaRoche, Tau SILK Consortium (Abbvie, Biogen, and Eli Lilly & Co), Centene, DIAN‐TU Pharma Consortium (Biogen, Eisai, Eli Lilly & Co, Janssen, Hoffman‐LaRoche/Genentech, and United Neuroscience). He has received royalties from and holds equity ownership interests in C2N Diagnostics. He has received consulting fees from Janssen, Eisai, AC Immune, Amgen, and Hoffman‐LaRoche and travel support from AC Immune and Hoffman‐LaRoche. He served on the advisory board of C2N Diagnostics and Hoffman‐LaRoche. Jason Hassenstab has received support outside the submitted work from NIA and BrightFocus Foundation. He has received consulting fees and honoraria/payments from Roche, Parabon Nanolabs, and NIA grants. He has received payment for serving on the Data Safety Monitoring Board (DSMB) for Mission AD and NIA grants. Sarah B. Berman has received support outside the submitted work from NIH and Michael J. Fox Foundation. She also served unpaid on the Scientific Advisory Committee of the Lewy Body Disease Association. Jasmeer P. Chhatwal has received support outside the submitted work from NIH/NIA and received consulting fees from Otsuka Pharmaceuticals. He also received travel funds from NIH grants and the Doris Duke Charitable Foundation. Adrian Danek has received support outside the submitted work from Advocacy for Neuroacanthocytosis Patients for whom he also serves in an unpaid leadership role. He has received honoraria/payments for lectures at Swiss hospitals, for expert witness testimony, and government supported travel. Anne M. Fagan has received support outside the submitted work from NIH/NIA and consulting fees from Diadem and Roche Diagnostics. Bernardino Ghetti has received support outside the submitted work from NIH/NIA and honoraria/payments from the University of Utah. Alison Goate has received support outside the submitted work from NIH, Rainwater Charitable Foundation, JPB Foundation, and the Neurodegeneration Consortium. She has received royalties from Athena Diagnostics and Taconic Industries. Mathias Jucker has received support outside the submitted work from German Research Foundation, Alz Cure, Novartis, and IMI2. He has also received consulting fees from Roche and Synapsis as well as honoraria/payments from Merz. Johannes Levin has received support outside the submitted work from DZNE (German center of neurodegenerative diseases). He has received consulting fees from Biogen as well as honoraria/payments from Bayer and Roche. He is compensated as Chief Medical Officer for MODAG GmbH and serves on the Scientific Advisory Board of Axon Neurosciences. Daniel S Marcus has received support outside the submitted work from NIH. He also holds stock in and received royalties from Radiologics. Eric McDade has received support outside the submitted work from NIA, Eli Lilly, Hoffman La Roche, and Janssen. He receives royalties from UpToDate and consulting fees for serving on DSMBs for Eli Lilly and Alector and as Scientific Advisory Board member for Alzamed. He received support for attending the Foundation Alzheimer's Scientific Advisory Board and received honoraria/payments from Eisai for a CME presentation. He has submitted patent US 17/05,985 entitled “Methods of Treating Based on Site‐Specific Tau Phosphorylation.” Krista L. Moulder has received support outside the submitted work from the Cure Alzheimer's Fund. James M. Noble has received support outside the submitted work from NIH/NIA and the Department of Defense (DOD). He also has patent pending for “Systems and methods for real‐time concussion diagnosis by electroencephalogram activity monitoring” (US20190298262A1). John M. Ringman has received support outside the submitted work from NIH/NIA. He served on the DSMB for RENEW LLC. Nick C. Fox has received consulting feed from Biogen, Roche, and Ionis outside the submitted work. He received tracer for in‐kind support from Eli Lilly and payment for serving on Biogen's DSMB and Roche's Scientific Advisory Board. Stephen Salloway has received support outside the submitted work from Lilly, Biogen, and Roche. He received consulting fees and travel support from Biogen, Amgen, Suven, Avid, Genentech, Roche, Acumen, Gemvax, Takeda, Bolden Therapeutics, Prothena, Alnylam, and Ono. He received honoraria/payments for educational events from P.E.R, Biogen, PlatformQ, WebMD, GME, and the Veteran's Administration. He served on advisory boards for Biogen and Acumen Scientific. Peter R. Schofield has received support outside the submitted work from the National Health and Medical Research Council of Australia, Medical Research Future Fund of Australia, and Spanish Internationalisation Network I‐Link Grant. He holds leadership roles in Neuroscience Research Australia and its foundation, the Health‐Science Alliance, the Schizophrenia Research Institute, the Australian Dementia Network Ltd, the Association of Australian Medical Research Institutes Ltd, the Australasian Neuroscience Society, and Business Events Sydney. He also served on the Steering Committee, Maridulu Budyari Gumal ‐ Sydney Partnership for Health Education, Research and Enterprise and the National Medical Advisory Panel of the Judith Jane Mason & Harold Stannett Williams Memorial Foundation. John C. Morris has received support outside the submitted work from NIH/NIA. He receives royalties from the Clinical Dementia Rating{\textregistered} and consulting fees from Barcelona Beta Brain Research Foundation Scientific Advisory Board and the Int'l Advisory Board, TS Srinivasan‐NIMHANS Knowledge Conclave. He received honoraria/payments for Grand Rounds at Montefiore Health Systems and travel support for the Srinvasan 40th Oration, Indian World Congress of Neurology, the Cure Alzheimer Board meeting (member), and the CBR Int'l Advisory board meeting. Publisher Copyright: {\textcopyright} 2021 the Alzheimer's Association.",

year = "2022",

month = oct,

doi = "10.1002/alz.12505",

language = "English",

volume = "18",

pages = "1754--1764",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

number = "10",

}

TY - JOUR

T1 - Different rates of cognitive decline in autosomal dominant and late-onset Alzheimer disease

AU - for the Dominantly Inherited Alzheimer's Network

AU - Buckles, Virginia D.

AU - Xiong, Chengjie

AU - Bateman, Randall J.

AU - Hassenstab, Jason

AU - Allegri, Ricardo

AU - Berman, Sarah B.

AU - Chhatwal, Jasmeer P.

AU - Danek, Adrian

AU - Fagan, Anne M.

AU - Ghetti, Bernardino

AU - Goate, Alison

AU - Graff-Radford, Neill

AU - Jucker, Mathias

AU - Levin, Johannes

AU - Marcus, Daniel S.

AU - Masters, Colin L.

AU - McCue, Lena

AU - McDade, Eric

AU - Mori, Hiroshi

AU - Moulder, Krista L.

AU - Noble, James M.

AU - Paumier, Katrina

AU - Preische, Oliver

AU - Ringman, John M.

AU - Fox, Nick C.

AU - Salloway, Stephen

AU - Schofield, Peter R.

AU - Martins, Ralph

AU - Vöglein, Jonathan

AU - Morris, John C.

N1 - Funding Information: DIAN data collection and sharing for this project was supported by The Dominantly Inherited Alzheimer Network (DIAN, U19AG032438) funded by the National Institute on Aging (NIA), the German Center for Neurodegenerative Diseases (DZNE), Raul Carrea Institute for Neurological Research (FLENI). Partial support by the Research and Development Grants for Dementia from Japan Agency for Medical Research and Development, AMED and NIHR UCL/UCLH Biomedical Research Centre and the MRC Dementias Platform UK (MR/L023784/1 and MR/009076/1). This manuscript has been reviewed by DIAN Study investigators for scientific content and consistency of data interpretation with previous DIAN Study publications. We acknowledge the altruism of the participants and their families and contributions of the DIAN research and support staff at each of the participating sites for their contributions to this study. The NACC database is funded by NIA/NIH Grant U24 AG072122. NACC data are contributed by the NIA‐funded ADRCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P50 AG047266 (PI Todd Golde, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Thomas Wisniewski, MD), P30 AG013854 (PI Robert Vassar, PhD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P50 AG005131 (PI James Brewer, MD, PhD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG053760 (PI Henry Paulson, MD, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 and P30 AG066530 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P30 AG049638 (PI Suzanne Craft, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P50 AG033514 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John Morris, MD), P50 AG047270 (PI Stephen Strittmatter, MD, PhD). Funding Information: Drs. Allegri, Graff‐Radford, Masters, McCue, Mori, Paumier, Preische, Martins, and Vöglein have nothing to disclose. Virginia D. Buckles received support as a consultant from Washington University in St. Louis. Chengjie Xiong has received grant support from NIH/NIA outside the submitted work. He also served on the University of Wisconsin Alzheimer's Disease Research Center External Advisory Committee. Randall J. Bateman has received support outside the submitted work from NIH/NIA, Avid Radiopharmaceuticals, Janssen, Eisai, Genentech, Eli Lilly & Co, Hoffman‐LaRoche, Tau SILK Consortium (Abbvie, Biogen, and Eli Lilly & Co), Centene, DIAN‐TU Pharma Consortium (Biogen, Eisai, Eli Lilly & Co, Janssen, Hoffman‐LaRoche/Genentech, and United Neuroscience). He has received royalties from and holds equity ownership interests in C2N Diagnostics. He has received consulting fees from Janssen, Eisai, AC Immune, Amgen, and Hoffman‐LaRoche and travel support from AC Immune and Hoffman‐LaRoche. He served on the advisory board of C2N Diagnostics and Hoffman‐LaRoche. Jason Hassenstab has received support outside the submitted work from NIA and BrightFocus Foundation. He has received consulting fees and honoraria/payments from Roche, Parabon Nanolabs, and NIA grants. He has received payment for serving on the Data Safety Monitoring Board (DSMB) for Mission AD and NIA grants. Sarah B. Berman has received support outside the submitted work from NIH and Michael J. Fox Foundation. She also served unpaid on the Scientific Advisory Committee of the Lewy Body Disease Association. Jasmeer P. Chhatwal has received support outside the submitted work from NIH/NIA and received consulting fees from Otsuka Pharmaceuticals. He also received travel funds from NIH grants and the Doris Duke Charitable Foundation. Adrian Danek has received support outside the submitted work from Advocacy for Neuroacanthocytosis Patients for whom he also serves in an unpaid leadership role. He has received honoraria/payments for lectures at Swiss hospitals, for expert witness testimony, and government supported travel. Anne M. Fagan has received support outside the submitted work from NIH/NIA and consulting fees from Diadem and Roche Diagnostics. Bernardino Ghetti has received support outside the submitted work from NIH/NIA and honoraria/payments from the University of Utah. Alison Goate has received support outside the submitted work from NIH, Rainwater Charitable Foundation, JPB Foundation, and the Neurodegeneration Consortium. She has received royalties from Athena Diagnostics and Taconic Industries. Mathias Jucker has received support outside the submitted work from German Research Foundation, Alz Cure, Novartis, and IMI2. He has also received consulting fees from Roche and Synapsis as well as honoraria/payments from Merz. Johannes Levin has received support outside the submitted work from DZNE (German center of neurodegenerative diseases). He has received consulting fees from Biogen as well as honoraria/payments from Bayer and Roche. He is compensated as Chief Medical Officer for MODAG GmbH and serves on the Scientific Advisory Board of Axon Neurosciences. Daniel S Marcus has received support outside the submitted work from NIH. He also holds stock in and received royalties from Radiologics. Eric McDade has received support outside the submitted work from NIA, Eli Lilly, Hoffman La Roche, and Janssen. He receives royalties from UpToDate and consulting fees for serving on DSMBs for Eli Lilly and Alector and as Scientific Advisory Board member for Alzamed. He received support for attending the Foundation Alzheimer's Scientific Advisory Board and received honoraria/payments from Eisai for a CME presentation. He has submitted patent US 17/05,985 entitled “Methods of Treating Based on Site‐Specific Tau Phosphorylation.” Krista L. Moulder has received support outside the submitted work from the Cure Alzheimer's Fund. James M. Noble has received support outside the submitted work from NIH/NIA and the Department of Defense (DOD). He also has patent pending for “Systems and methods for real‐time concussion diagnosis by electroencephalogram activity monitoring” (US20190298262A1). John M. Ringman has received support outside the submitted work from NIH/NIA. He served on the DSMB for RENEW LLC. Nick C. Fox has received consulting feed from Biogen, Roche, and Ionis outside the submitted work. He received tracer for in‐kind support from Eli Lilly and payment for serving on Biogen's DSMB and Roche's Scientific Advisory Board. Stephen Salloway has received support outside the submitted work from Lilly, Biogen, and Roche. He received consulting fees and travel support from Biogen, Amgen, Suven, Avid, Genentech, Roche, Acumen, Gemvax, Takeda, Bolden Therapeutics, Prothena, Alnylam, and Ono. He received honoraria/payments for educational events from P.E.R, Biogen, PlatformQ, WebMD, GME, and the Veteran's Administration. He served on advisory boards for Biogen and Acumen Scientific. Peter R. Schofield has received support outside the submitted work from the National Health and Medical Research Council of Australia, Medical Research Future Fund of Australia, and Spanish Internationalisation Network I‐Link Grant. He holds leadership roles in Neuroscience Research Australia and its foundation, the Health‐Science Alliance, the Schizophrenia Research Institute, the Australian Dementia Network Ltd, the Association of Australian Medical Research Institutes Ltd, the Australasian Neuroscience Society, and Business Events Sydney. He also served on the Steering Committee, Maridulu Budyari Gumal ‐ Sydney Partnership for Health Education, Research and Enterprise and the National Medical Advisory Panel of the Judith Jane Mason & Harold Stannett Williams Memorial Foundation. John C. Morris has received support outside the submitted work from NIH/NIA. He receives royalties from the Clinical Dementia Rating® and consulting fees from Barcelona Beta Brain Research Foundation Scientific Advisory Board and the Int'l Advisory Board, TS Srinivasan‐NIMHANS Knowledge Conclave. He received honoraria/payments for Grand Rounds at Montefiore Health Systems and travel support for the Srinvasan 40th Oration, Indian World Congress of Neurology, the Cure Alzheimer Board meeting (member), and the CBR Int'l Advisory board meeting. Publisher Copyright: © 2021 the Alzheimer's Association.

PY - 2022/10

Y1 - 2022/10

N2 - As prevention trials advance with autosomal dominant Alzheimer disease (ADAD) participants, understanding the similarities and differences between ADAD and “sporadic” late-onset AD (LOAD) is critical to determine generalizability of findings between these cohorts. Cognitive trajectories of ADAD mutation carriers (MCs) and autopsy-confirmed LOAD individuals were compared to address this question. Longitudinal rates of change on cognitive measures were compared in ADAD MCs (n = 310) and autopsy-confirmed LOAD participants (n = 163) before and after symptom onset (estimated/observed). LOAD participants declined more rapidly in the presymptomatic (preclinical) period and performed more poorly at symptom onset than ADAD participants on a cognitive composite. After symptom onset, however, the younger ADAD MCs declined more rapidly. The similar but not identical cognitive trajectories (declining but at different rates) for ADAD and LOAD suggest common AD pathologies but with some differences.

AB - As prevention trials advance with autosomal dominant Alzheimer disease (ADAD) participants, understanding the similarities and differences between ADAD and “sporadic” late-onset AD (LOAD) is critical to determine generalizability of findings between these cohorts. Cognitive trajectories of ADAD mutation carriers (MCs) and autopsy-confirmed LOAD individuals were compared to address this question. Longitudinal rates of change on cognitive measures were compared in ADAD MCs (n = 310) and autopsy-confirmed LOAD participants (n = 163) before and after symptom onset (estimated/observed). LOAD participants declined more rapidly in the presymptomatic (preclinical) period and performed more poorly at symptom onset than ADAD participants on a cognitive composite. After symptom onset, however, the younger ADAD MCs declined more rapidly. The similar but not identical cognitive trajectories (declining but at different rates) for ADAD and LOAD suggest common AD pathologies but with some differences.

KW - Alzheimer disease

KW - autosomal dominant Alzheimer disease

KW - cognitive

KW - comorbidities

KW - late-onset Alzheimer disease

UR - http://www.scopus.com/inward/record.url?scp=85120479572&partnerID=8YFLogxK

U2 - 10.1002/alz.12505

DO - 10.1002/alz.12505

M3 - Article

C2 - 34854530

AN - SCOPUS:85120479572

SN - 1552-5260

VL - 18

SP - 1754

EP - 1764

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 10

ER -

Different rates of cognitive decline in autosomal dominant and late-onset Alzheimer disease

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Keywords

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