TY - JOUR
T1 - Decline in cognitively complex everyday activities accelerates along the Alzheimer’s disease continuum
AU - for the Alzheimer Disease Neuroimaging Initiative, National Alzheimer’s Coordinating Center, the Harvard Aging Brain Study, the Alzheimer Dementia Cohort
AU - Dubbelman, Mark A.
AU - Jutten, Roos J.
AU - Tomaszewski Farias, Sarah E.
AU - Amariglio, Rebecca E.
AU - Buckley, Rachel F.
AU - Visser, Pieter Jelle
AU - Rentz, Dorene M.
AU - Johnson, Keith A.
AU - Properzi, Michael J.
AU - Schultz, Aaron
AU - Donovan, Nancy
AU - Gatchell, Jennifer R.
AU - Teunissen, Charlotte E.
AU - Van Berckel, Bart N.M.
AU - Van der Flier, Wiesje M.
AU - Sperling, Reisa A.
AU - Papp, Kathryn V.
AU - Scheltens, Philip
AU - Marshall, Gad A.
AU - Sikkes, Sietske A.M.
N1 - Funding Information:
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:
Data collection and sharing for this project was 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 ScaleDiagnostics, 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 ( http://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 Neuroimaging at the University of Southern California.
Funding Information:
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).
Funding Information:
The Alzheimer Center Amsterdam is supported by Alzheimer Nederland and Stichting VUmc Fonds. The clinical database structure of the Amsterdam Dementia Cohort (ADC) was developed with funding from Stichting Dioraphte.
Funding Information:
The work for the EMIF cohorts has received support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking (EMIF grant no. 115372). It also received in kind sponsoring of the CSF assay from ADx NeuroSciences and Euroimmun, and the PET-tracer 18F-flutemetamol from GE Healthcare. Acknowledgements
Funding Information:
MAD, RJJ, SETF, REA, RFB, PJV, DMR, KAJ, MJP, AS, ND, JRG, BNMB, and RAS 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, and Roche. KVP has served as a paid consultant for Biogen.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Background: Impairment in daily functioning is a clinical hallmark of dementia. Difficulties with “instrumental activities of daily living” (IADL) seem to increase gradually over the course of Alzheimer’s disease (AD), before dementia onset. However, it is currently not well established how difficulties develop along the preclinical and prodromal stages of AD. We aimed to investigate the trajectories of decline in IADL performance, as reported by a study partner, along the early stages of AD. Methods: In a longitudinal multicenter study, combining data from community-based and memory clinic cohorts, we included 1555 individuals (mean age 72.5 ± 7.8 years; 50% female) based on availability of amyloid biomarkers, longitudinal IADL data, and clinical information at baseline. Median follow-up duration was 2.1 years. All amyloid-positive participants (n = 982) were classified into the National Institute on Aging–Alzheimer’s Association (NIA-AA) clinical stages ranging from preclinical AD (1) to overt dementia (4+). Cognitively normal amyloid-negative individuals (n = 573) served as a comparison group. The total scores of three study-partner reported IADL questionnaires were standardized. Results: The rate of decline in cognitively normal (stage 1) individuals with and without abnormal amyloid did not differ (p =.453). However, from stage 2 onwards, decline was significantly faster in individuals on the AD continuum (B [95%CI] = − 0.32 [− 0.55, − 0.09], p =.007). The rate of decline increased with each successive stage: one standard deviation (SD) unit per year in stage 3 (− 1.06 [− 1.27, − 0.85], p <.001) and nearly two SD units per year in stage 4+ (1.93 [− 2.19, − 1.67], p <.001). Overall, results were similar between community-based and memory clinic study cohorts. Conclusions: Our results suggest that the rate of functional decline accelerates along the AD continuum, as shown by steeper rates of decline in each successive NIA-AA clinical stage. These results imply that incremental changes in function are a meaningful measure for early disease monitoring. Combined with the low-cost assessment, this advocates the use of these functional questionnaires for capturing the effects of early AD-related cognitive decline on daily life.
AB - Background: Impairment in daily functioning is a clinical hallmark of dementia. Difficulties with “instrumental activities of daily living” (IADL) seem to increase gradually over the course of Alzheimer’s disease (AD), before dementia onset. However, it is currently not well established how difficulties develop along the preclinical and prodromal stages of AD. We aimed to investigate the trajectories of decline in IADL performance, as reported by a study partner, along the early stages of AD. Methods: In a longitudinal multicenter study, combining data from community-based and memory clinic cohorts, we included 1555 individuals (mean age 72.5 ± 7.8 years; 50% female) based on availability of amyloid biomarkers, longitudinal IADL data, and clinical information at baseline. Median follow-up duration was 2.1 years. All amyloid-positive participants (n = 982) were classified into the National Institute on Aging–Alzheimer’s Association (NIA-AA) clinical stages ranging from preclinical AD (1) to overt dementia (4+). Cognitively normal amyloid-negative individuals (n = 573) served as a comparison group. The total scores of three study-partner reported IADL questionnaires were standardized. Results: The rate of decline in cognitively normal (stage 1) individuals with and without abnormal amyloid did not differ (p =.453). However, from stage 2 onwards, decline was significantly faster in individuals on the AD continuum (B [95%CI] = − 0.32 [− 0.55, − 0.09], p =.007). The rate of decline increased with each successive stage: one standard deviation (SD) unit per year in stage 3 (− 1.06 [− 1.27, − 0.85], p <.001) and nearly two SD units per year in stage 4+ (1.93 [− 2.19, − 1.67], p <.001). Overall, results were similar between community-based and memory clinic study cohorts. Conclusions: Our results suggest that the rate of functional decline accelerates along the AD continuum, as shown by steeper rates of decline in each successive NIA-AA clinical stage. These results imply that incremental changes in function are a meaningful measure for early disease monitoring. Combined with the low-cost assessment, this advocates the use of these functional questionnaires for capturing the effects of early AD-related cognitive decline on daily life.
KW - Alzheimer’s disease
KW - clinical stages
KW - functional impairment
KW - instrumental activities of daily living
UR - http://www.scopus.com/inward/record.url?scp=85094857848&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85094857848&partnerID=8YFLogxK
U2 - 10.1186/s13195-020-00706-2
DO - 10.1186/s13195-020-00706-2
M3 - Article
C2 - 33121534
AN - SCOPUS:85094857848
VL - 12
JO - Alzheimer's Research and Therapy
JF - Alzheimer's Research and Therapy
SN - 1758-9193
IS - 1
M1 - 138
ER -