Abstract
Objective: Alzheimer's disease (AD) studies are increasingly targeting earlier (pre)clinical populations, in which the expected degree of observable cognitive decline over a certain time interval is reduced as compared to the dementia stage. Consequently, endpoints to capture early cognitive changes require refinement. We aimed to determine the sensitivity to decline of widely applied neuropsychological tests at different clinical stages of AD as outlined in the National Institute on Aging - Alzheimer's Association (NIA-AA) research framework. Method: Amyloid-positive individuals (as determined by positron emission tomography or cerebrospinal fluid) with longitudinal neuropsychological assessments available were included from four well-defined study cohorts and subsequently classified among the NIA-AA stages. For each stage, we investigated the sensitivity to decline of 17 individual neuropsychological tests using linear mixed models. Results: 1103 participants (age = 70.54 ± 8.7, 47% female) were included: n = 120 Stage 1, n = 206 Stage 2, n = 467 Stage 3 and n = 309 Stage 4. Neuropsychological tests were differentially sensitive to decline across stages. For example, Category Fluency captured significant 1-year decline as early as Stage 1 (β = -.58, p < .001). Word List Delayed Recall (β = -.22, p < .05) and Trail Making Test (β = 6.2, p < .05) became sensitive to 1-year decline in Stage 2, whereas the Mini-Mental State Examination did not capture 1- year decline until Stage 3 (β = -1.13, p < .001) and 4 (β = -2.23, p < .001). Conclusions: We demonstrated that commonly used neuropsychological tests differ in their ability to capture decline depending on clinical stage within the AD continuum (preclinical to dementia). This implies that stage-specific cognitive endpoints are needed to accurately assess disease progression and increase the chance of successful treatment evaluation in AD.
| Original language | English |
|---|---|
| Pages (from-to) | 426-438 |
| Number of pages | 13 |
| Journal | Journal of the International Neuropsychological Society |
| Volume | 27 |
| Issue number | 5 |
| Early online date | 2020 |
| DOIs | |
| Publication status | Published - 1 May 2021 |
Keywords
- Alzheimer's disease
- Cognitive decline
- Disease progression
- Outcome measures
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In: Journal of the International Neuropsychological Society, Vol. 27, No. 5, 01.05.2021, p. 426-438.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Identifying sensitive measures of cognitive decline at different clinical stages of alzheimer's disease
AU - Jutten, Roos J.
AU - Sikkes, Sietske A. M.
AU - Amariglio, Rebecca E.
AU - Alzheimer Disease Neuroimaging Initiative
AU - Buckley, Rachel F.
AU - Properzi, Michael J.
AU - Marshall, Gad A.
AU - Rentz, Dorene M.
AU - National Alzheimer's Coordinating Center
AU - Johnson, Keith A.
AU - Harvard Aging Brain Study
AU - Teunissen, Charlotte E.
AU - Alzheimer Dementia Cohort
AU - van Berckel, Bart N. M.
AU - van der Flier, Wiesje M.
AU - Scheltens, Philip
AU - Sperling, Reisa A.
AU - Papp, Kathryn V.
N1 - Funding Information: ADC: The Alzheimer Center Amsterdam is supported by Alzheimer Nederland and Stichting VUMC funds. Research of the Alzheimer Center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. The clinical database structure was developed with funding from Stichting Dioraphte. The SCIENCe project is supported by a research grant from Gieskes-Strijbis fonds. The present study is supported by a grant from Memorabel (grant no. 733050205), which is the research program of the Dutch Deltaplan for Dementia. Funding Information: ADNI: Data collection and sharing for this project were funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol, Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann,La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( www.fnih.org ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Funding Information: RJJ, REA, RFB, MJP, DMR, KAJ, BNMB, PS and RS report no disclosures relevant to this manuscript. SAMS is supported by grants from JPND and Zon-MW and has provided consultancy services in the past 2 years for Nutricia and Takeda. All funds were paid to her institution. GAM has received research salary support from Eisai Inc., Eli Lilly and Company, Janssen Alzheimer Immunotherapy, Novartis, and Genentech. Additionally, GAM has served as a consultant for Grifols Shared Services North America, Inc., Eisai Inc., and Pfizer. WMF holds the Pasman chair. CET received grants from the European Commission, the Dutch Research Council (ZonMW), Association of Frontotemporal Dementia/Alzheimer’s Drug Discovery Foundation, The Weston Brain Institute, Alzheimer Nederland. CET has functioned in advisory boards of Roche, received non-financial support in the form of research consumables from ADxNeurosciences and Euroimmun, performed contract research or received grants from Probiodrug, Biogen, Esai, Toyama, Janssen prevention center, Boehringer, AxonNeurosciences, EIP farma, PeopleBio, Roche. KVP has served as a paid consultant for Biogen. Funding Information: HABS: The Harvard Aging Brain Study is funded by the National Institute on Aging (P01AG036694; Principal Investigators Reisa Sperling, Keith Johnson) with additional support from several philanthropic organizations. KVP (1K23AG053422-01) is supported by a K23 award from NIA and an award from the Alzheimer’s Association. Funding Information: NACC: The NACC database is funded by NIA/NIH grant U01 AG016976. NACC data are contributed by the NIA-funded ADCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P30 AG062428-01 (PI James Leverenz, 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), P30 AG062421-01 (PI Bradley Hyman, MD, PhD), P30 AG062422-01 (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), P30 AG062429-01(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 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P30 AG049638 (PI Suzanne Craft, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P30 AG062715-01 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John Morris, MD), and P50 AG047270 (PI Stephen Strittmatter, MD, PhD). ACKNOWLEDGEMENTS Publisher Copyright: Copyright © INS. Published by Cambridge University Press, 2020.
PY - 2021/5/1
Y1 - 2021/5/1
N2 - Objective: Alzheimer's disease (AD) studies are increasingly targeting earlier (pre)clinical populations, in which the expected degree of observable cognitive decline over a certain time interval is reduced as compared to the dementia stage. Consequently, endpoints to capture early cognitive changes require refinement. We aimed to determine the sensitivity to decline of widely applied neuropsychological tests at different clinical stages of AD as outlined in the National Institute on Aging - Alzheimer's Association (NIA-AA) research framework. Method: Amyloid-positive individuals (as determined by positron emission tomography or cerebrospinal fluid) with longitudinal neuropsychological assessments available were included from four well-defined study cohorts and subsequently classified among the NIA-AA stages. For each stage, we investigated the sensitivity to decline of 17 individual neuropsychological tests using linear mixed models. Results: 1103 participants (age = 70.54 ± 8.7, 47% female) were included: n = 120 Stage 1, n = 206 Stage 2, n = 467 Stage 3 and n = 309 Stage 4. Neuropsychological tests were differentially sensitive to decline across stages. For example, Category Fluency captured significant 1-year decline as early as Stage 1 (β = -.58, p < .001). Word List Delayed Recall (β = -.22, p < .05) and Trail Making Test (β = 6.2, p < .05) became sensitive to 1-year decline in Stage 2, whereas the Mini-Mental State Examination did not capture 1- year decline until Stage 3 (β = -1.13, p < .001) and 4 (β = -2.23, p < .001). Conclusions: We demonstrated that commonly used neuropsychological tests differ in their ability to capture decline depending on clinical stage within the AD continuum (preclinical to dementia). This implies that stage-specific cognitive endpoints are needed to accurately assess disease progression and increase the chance of successful treatment evaluation in AD.
AB - Objective: Alzheimer's disease (AD) studies are increasingly targeting earlier (pre)clinical populations, in which the expected degree of observable cognitive decline over a certain time interval is reduced as compared to the dementia stage. Consequently, endpoints to capture early cognitive changes require refinement. We aimed to determine the sensitivity to decline of widely applied neuropsychological tests at different clinical stages of AD as outlined in the National Institute on Aging - Alzheimer's Association (NIA-AA) research framework. Method: Amyloid-positive individuals (as determined by positron emission tomography or cerebrospinal fluid) with longitudinal neuropsychological assessments available were included from four well-defined study cohorts and subsequently classified among the NIA-AA stages. For each stage, we investigated the sensitivity to decline of 17 individual neuropsychological tests using linear mixed models. Results: 1103 participants (age = 70.54 ± 8.7, 47% female) were included: n = 120 Stage 1, n = 206 Stage 2, n = 467 Stage 3 and n = 309 Stage 4. Neuropsychological tests were differentially sensitive to decline across stages. For example, Category Fluency captured significant 1-year decline as early as Stage 1 (β = -.58, p < .001). Word List Delayed Recall (β = -.22, p < .05) and Trail Making Test (β = 6.2, p < .05) became sensitive to 1-year decline in Stage 2, whereas the Mini-Mental State Examination did not capture 1- year decline until Stage 3 (β = -1.13, p < .001) and 4 (β = -2.23, p < .001). Conclusions: We demonstrated that commonly used neuropsychological tests differ in their ability to capture decline depending on clinical stage within the AD continuum (preclinical to dementia). This implies that stage-specific cognitive endpoints are needed to accurately assess disease progression and increase the chance of successful treatment evaluation in AD.
KW - Alzheimer's disease
KW - Cognitive decline
KW - Disease progression
KW - Outcome measures
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85093858950&origin=inward
U2 - https://doi.org/10.1017/S1355617720000934
DO - https://doi.org/10.1017/S1355617720000934
M3 - Article
C2 - 33046162
SN - 1355-6177
VL - 27
SP - 426
EP - 438
JO - Journal of the International Neuropsychological Society
JF - Journal of the International Neuropsychological Society
IS - 5
ER -