Evidence map›Paper›PMID 33121534›Full record

ArticleAlzheimer's research & therapy2020

Decline in cognitively complex everyday activities accelerates along the Alzheimer's disease continuum.

Mark A Dubbelman, Roos J Jutten, Sarah E Tomaszewski Farias, Rebecca E Amariglio, Rachel F Buckley, Pieter Jelle Visser, Dorene M Rentz, Keith A Johnson, Michael J Properzi, Aaron Schultz and 11 more

Open access · goldAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
2.6field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

47 citing papers in PubMed, 54 citations in OpenAlex.

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  15. Functional capacity in Peruvian people with Alzheimer's disease and frontotemporal dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  16. Article
  17. Predicting the onset of dementia with longitudinal performance-based measures of physical function.The journals of gerontology. Series B, Psychological sciences and social sciences · 2025
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 6 institutions in 3 countries.

Mark A DubbelmanDepartment of Neurology, Amsterdam Neuroscience, Alzheimer Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam UMC, location VUmc, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands. m.dubbelman@amsterdamumc.nl.ORCID 0000-0002-5708-4925
Roos J JuttenDepartment of Neurology, Amsterdam Neuroscience, Alzheimer Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam UMC, location VUmc, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands.
Sarah E Tomaszewski FariasDepartment of Neurology, University of California, Davis, Davis, CA, USA.
Rebecca E AmariglioDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Rachel F BuckleyDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Pieter Jelle VisserDepartment of Neurology, Amsterdam Neuroscience, Alzheimer Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam UMC, location VUmc, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands.
Dorene M RentzDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Keith A JohnsonDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Michael J ProperziDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Aaron SchultzDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Nancy DonovanDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Jennifer R GatchellDepartment of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Charlotte E TeunissenNeurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Bart N M Van BerckelDepartment of Radiology and Nuclear Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Wiesje M Van der FlierDepartment of Neurology, Amsterdam Neuroscience, Alzheimer Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam UMC, location VUmc, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands.
Reisa A SperlingDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Kathryn V PappDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Philip ScheltensDepartment of Neurology, Amsterdam Neuroscience, Alzheimer Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam UMC, location VUmc, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands.
Gad A MarshallDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Sietske A M SikkesDepartment of Neurology, Amsterdam Neuroscience, Alzheimer Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam UMC, location VUmc, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands.
Alzheimer Disease Neuroimaging Initiative, National Alzheimer’s Coordinating Center, the Harvard Aging Brain Study, the Alzheimer Dementia Cohort
Brigham and Women's Hospital · USAmsterdam Neuroscience · NLHarvard University · USAmsterdam University Medical Centers · NLMaastricht University · NLUniversity of California, Davis · US

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
Vascular factors, physical activity, and inflammation as modulators of neurodegenerative and cognitive trajectories (Project 2)P01AG036694 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Hyun-Sik Yang · 2010 to 2026
$50.2M
Research Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI STEVEN E ARNOLD · 2019 to 2026
$36.5M
Optimizing semantic memory measures to detect tau- and amyloid- related cognitive changeK23AG053422 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI PAPP, KATHRYN VICTORIA · 2016 to 2020
$681k
NIA NIH HHS 1K23AG053422-01NIA NIH HHS K23 AG053422NIA NIH HHS P01 AG036694NIA NIH HHS P30 AG062421NIA NIH HHS U01 AG024904
6 · The paper itself

Abstract

backgroundImpairment 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.

methodsIn 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.

resultsThe 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.

conclusionsOur 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.

Indexed as

Alzheimer DiseaseCognitive DysfunctionActivities of Daily LivingAgedAged, 80 and overAmyloid beta-PeptidesDisease ProgressionFemaleHumansLongitudinal StudiesMaleMiddle AgedProdromal SymptomsAmyloid beta-PeptidesAlzheimer’s diseaseclinical stagesfunctional impairmentinstrumental activities of daily living

Identifiers

PMID33121534
PMCPMC7597034
OpenAlexW3097135080

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.