Abstract
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.
| Original language | English |
|---|---|
| Article number | 138 |
| Pages (from-to) | 1-11 |
| Number of pages | 11 |
| Journal | Alzheimer's Research and Therapy |
| Volume | 12 |
| Issue number | 1 |
| Early online date | 29 Oct 2020 |
| DOIs | |
| Publication status | Published - 1 Dec 2020 |
Funding
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 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. 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. 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). 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. The authors thank all patients and participants in the studies, as well as everyone involved in data collection and data sharing. Part of the data used in preparation of this article were obtained from the Alzheimer Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp ,content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.
| Funders | Funder number |
|---|---|
| DOD ADNI | |
| EU/EFPIA | 115372 |
| Euroimmun | |
| National Institutes of Health | U01 AG016976, U01 AG024904 |
| U.S. Department of Defense | W81XWH-12-2-0012 |
| National Institute on Aging | P01AG036694, 1K23AG053422-01 |
| National Institute of Biomedical Imaging and Bioengineering | |
| Alzheimer's Association | |
| Eli Lilly and Company | |
| F. Hoffmann-La Roche | |
| Alzheimer's Disease Neuroimaging Initiative |
Keywords
- Alzheimer’s disease
- clinical stages
- functional impairment
- instrumental activities of daily living
