TY - JOUR
T1 - Decline in cognitively complex everyday activities accelerates along the Alzheimer's disease continuum
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.
AU - Alzheimer's Disease Neuroimaging Initiative
AU - National Alzheimer’s Coordinating Center
AU - Harvard Aging Brain Study
AU - Alzheimer Dementia Cohort
N1 - 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 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:
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.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/10/29
Y1 - 2020/10/29
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’
KW - s disease
KW - functional impairment
KW - instrumental activities of daily living
KW - clinical stages
KW - INSTRUMENTAL ACTIVITIES
KW - FUNCTIONAL-ACTIVITIES
KW - PREDICT PROGRESSION
KW - OLDER-ADULTS
KW - DEMENTIA
KW - DISCRIMINATE
KW - PERFORMANCE
KW - IMPAIRMENT
KW - DIAGNOSIS
KW - QUESTIONNAIRE
U2 - 10.1186/s13195-020-00706-2
DO - 10.1186/s13195-020-00706-2
M3 - Article
C2 - 33121534
SN - 1758-9193
VL - 12
JO - Alzheimer's Research & Therapy
JF - Alzheimer's Research & Therapy
IS - 1
M1 - 138
ER -