TY - JOUR
T1 - Research diagnostic criteria for Alzheimer’s disease: findings from the LipiDiDiet randomized controlled trial
AU - Rosenberg, Anna
AU - Solomon, Alina
AU - Soininen, Hilkka
AU - Visser, Pieter Jelle
AU - Blennow, Kaj
AU - Hartmann, Tobias
AU - Kivipelto, Miia
AU - on behalf of the LipiDiDiet clinical study group
AU - Hallikainen, Ilona
AU - Hallikainen, Merja
AU - Helisalmi, Seppo
AU - Lappalainen, Tarja
AU - Liu, Yawu
AU - Paajanen, Teemu
AU - Wahlund, Lars-Olof
AU - Freund-Levi, Yvonne
AU - Hagman, G. ran
AU - Fassbender, Klaus
AU - Riemenschneider, Matthias
AU - Grimm, Marcus O. W.
AU - Klees-Rollmann, Aline
AU - Luley, Maxine
AU - Lyros, Epameinondas
AU - Schomburg, Robert
AU - Ramelli, Daniela
AU - Kennel, Jennifer
AU - Frölich, Lutz
AU - Hausner, Lucrezia
AU - Laske, Christoph
AU - Leyhe, Thomas
AU - Mychajliw, Christian
AU - Koehler, Niklas
AU - Schiekofer, Stephan
AU - Klünemann, Hans
AU - Schröder, Johannes
AU - Lütjohann, Dieter
AU - Scheltens, Philip
AU - van Rossum, Ineke
AU - Scheltens, Nienke
AU - Bertens, Daniela
AU - ten Kate, Mara
AU - Barkhof, Frederik
AU - Ingala, Silvia
AU - Henselmans, Johanna M. L.
AU - Roks, Gerwin
AU - van Hees, Anneke M. J.
AU - van Oudenhoven, Floor M.
AU - Hendrix, Suzanne B.
AU - Ellison, Noel
N1 - Funding Information: We sincerely thank all participants enrolled in the study and their families. Members of the LipiDiDiet clinical study group: Hilkka Soininen, Ilona Hallikainen, Merja Hallikainen, Seppo Helisalmi, Tarja Lappalainen, Yawu Liu, Teemu Paajanen (University of Eastern Finland, Kuopio, Finland); Miia Kivipelto, Alina Solomon, Lars-Olof Wahlund, Yvonne Freund-Levi, G?ran Hagman (Karolinska University Hospital, Stockholm, Sweden); Kaj Blennow (University of Gothenburg, Gothenburg, Sweden); Tobias Hartmann, Klaus Fassbender, Matthias Riemenschneider, Marcus OW Grimm, Aline Klees-Rollmann, Maxine Luley, Epameinondas Lyros, Robert Schomburg, Daniela Ramelli, Jennifer Kennel (Saarland University, Homburg, Germany); Lutz Fr?lich, Lucrezia Hausner (Central Institute of Mental Health, Mannheim, Germany); Christoph Laske, Thomas Leyhe, Christian Mychajliw, Niklas Koehler (University Hospital of T?bingen, T?bingen, Germany); Stephan Schiekofer, Hans Kl?nemann (University Hospital Regensburg, Regensburg, Germany); Johannes Schr?der (Heidelberg University Hospital, Heidelberg, Germany); Dieter L?tjohann (Universit?tsklinikum Bonn, Bonn, Germany); Pieter Jelle Visser, Philip Scheltens, Ineke van Rossum, Nienke Scheltens, Daniela Bertens, Mara ten Kate, Frederik Barkhof, Silvia Ingala (VU University Medical Center, Amsterdam, the Netherlands); Johanna ML Henselmans (Antonius Hospital, Woerden, the Netherlands); Gerwin Roks (St. Elisabeth Hospital, Tilburg, the Netherlands); Anneke MJ van Hees, Floor M van Oudenhoven (Danone Nutricia Research, Utrecht, the Netherlands); Suzanne B Hendrix, Noel Ellison (Pentara Corporation, Millcreek, UT, USA). Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Background: To explore the utility of the International Working Group (IWG)-1 criteria in recruitment for Alzheimer’s disease (AD) clinical trials, we applied the more recently proposed research diagnostic criteria to individuals enrolled in a randomized controlled prevention trial (RCT) and assessed their disease progression. Methods: The multinational LipiDiDiet RCT targeted 311 individuals with IWG-1 defined prodromal AD. Based on centrally analyzed baseline biomarkers, participants were classified according to the IWG-2 and National Institute on Aging–Alzheimer’s Association (NIA-AA) 2011 and 2018 criteria. Linear mixed models were used to investigate the 2-year change in cognitive and functional performance (Neuropsychological Test Battery NTB Z scores, Clinical Dementia Rating-Sum of Boxes CDR-SB) (criteria × time interactions; baseline score, randomization group, sex, Mini-Mental State Examination (MMSE), and age also included in the models). Cox models adjusted for randomization group, MMSE, sex, age, and study site were used to investigate the risk of progression to dementia over 2 years. Results: In total, 88%, 86%, and 69% of participants had abnormal cerebrospinal fluid (CSF) β-amyloid, total tau, and phosphorylated tau, respectively; 64% had an A+T+N+ profile (CSF available for N = 107). Cognitive-functional decline appeared to be more pronounced in the IWG-2 prodromal AD, NIA-AA 2011 high and intermediate AD likelihood, and NIA-AA 2018 AD groups, but few significant differences were observed between the groups within each set of criteria. Hazard ratio (95% CI) for dementia was 4.6 (1.6–13.7) for IWG-2 prodromal AD (reference group no prodromal AD), 7.4 (1.0–54.7) for NIA-AA 2011 high AD likelihood (reference group suspected non-AD pathology SNAP), and 9.4 (1.2–72.7) for NIA-AA 2018 AD (reference group non-Alzheimer’s pathologic change). Compared with the NIA-AA 2011 high AD likelihood group (abnormal β-amyloid and neuronal injury markers), disease progression was similar in the intermediate AD likelihood group (medial temporal lobe atrophy; no CSF available). Conclusions: Despite being less restrictive than the other criteria, the IWG-1 criteria reliably identified individuals with AD pathology. More pragmatic and easily applicable selection criteria might be preferred due to feasibility in certain situations, e.g., in multidomain prevention trials that do not specifically target β-amyloid/tau pathologies. Trial registration: Netherlands Trial Register, NL1620. Registered on 9 March 2009.
AB - Background: To explore the utility of the International Working Group (IWG)-1 criteria in recruitment for Alzheimer’s disease (AD) clinical trials, we applied the more recently proposed research diagnostic criteria to individuals enrolled in a randomized controlled prevention trial (RCT) and assessed their disease progression. Methods: The multinational LipiDiDiet RCT targeted 311 individuals with IWG-1 defined prodromal AD. Based on centrally analyzed baseline biomarkers, participants were classified according to the IWG-2 and National Institute on Aging–Alzheimer’s Association (NIA-AA) 2011 and 2018 criteria. Linear mixed models were used to investigate the 2-year change in cognitive and functional performance (Neuropsychological Test Battery NTB Z scores, Clinical Dementia Rating-Sum of Boxes CDR-SB) (criteria × time interactions; baseline score, randomization group, sex, Mini-Mental State Examination (MMSE), and age also included in the models). Cox models adjusted for randomization group, MMSE, sex, age, and study site were used to investigate the risk of progression to dementia over 2 years. Results: In total, 88%, 86%, and 69% of participants had abnormal cerebrospinal fluid (CSF) β-amyloid, total tau, and phosphorylated tau, respectively; 64% had an A+T+N+ profile (CSF available for N = 107). Cognitive-functional decline appeared to be more pronounced in the IWG-2 prodromal AD, NIA-AA 2011 high and intermediate AD likelihood, and NIA-AA 2018 AD groups, but few significant differences were observed between the groups within each set of criteria. Hazard ratio (95% CI) for dementia was 4.6 (1.6–13.7) for IWG-2 prodromal AD (reference group no prodromal AD), 7.4 (1.0–54.7) for NIA-AA 2011 high AD likelihood (reference group suspected non-AD pathology SNAP), and 9.4 (1.2–72.7) for NIA-AA 2018 AD (reference group non-Alzheimer’s pathologic change). Compared with the NIA-AA 2011 high AD likelihood group (abnormal β-amyloid and neuronal injury markers), disease progression was similar in the intermediate AD likelihood group (medial temporal lobe atrophy; no CSF available). Conclusions: Despite being less restrictive than the other criteria, the IWG-1 criteria reliably identified individuals with AD pathology. More pragmatic and easily applicable selection criteria might be preferred due to feasibility in certain situations, e.g., in multidomain prevention trials that do not specifically target β-amyloid/tau pathologies. Trial registration: Netherlands Trial Register, NL1620. Registered on 9 March 2009.
KW - Alzheimer’s disease
KW - Biomarkers
KW - Cerebrospinal fluid
KW - Disease progression
KW - Early diagnosis
KW - Prevention
KW - Prodromal Alzheimer’s disease
KW - Randomized controlled trial
KW - Research criteria
UR - http://www.scopus.com/inward/record.url?scp=85103484754&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/s13195-021-00799-3
DO - https://doi.org/10.1186/s13195-021-00799-3
M3 - Article
C2 - 33766132
SN - 1758-9193
VL - 13
JO - Alzheimer's Research & Therapy
JF - Alzheimer's Research & Therapy
IS - 1
M1 - 64
ER -