The DOI matches its Crossref record; 70 of the 70 references it cites were found in a registry or an index.
Circadian Rest-Activity Pattern Changes in Aging and Preclinical Alzheimer Disease
Open accessAbstract
Importance: Circadian rhythm disturbances occur in symptomatic Alzheimer disease (AD) and have been hypothesized to contribute to disease pathogenesis. However, it is unknown whether circadian changes occur during the presymptomatic phase of the disease. Objective: To examine the associations between circadian function, aging, and preclinical AD pathology in cognitively normal adults. Design, Setting, and Participants: This cross-sectional study was conducted using community volunteers from the Knight Alzheimer's Disease Research Center at Washington University in St Louis. Cognitively normal participants (n = 205) underwent 7 to 14 days of actigraphy in their home environment between 2010 and 2012, in addition to clinical assessment, amyloid imaging with Pittsburgh Compound B (PiB), and cerebrospinal fluid biomarker collection. Data collected from 3 years before to 6 months after actigraphy were included. Sixteen participants were excluded owing to incomplete data collection. Main Outcomes and Measures: Circadian rhythm analysis was performed on actigraphy data using 3 methods: cosinor, nonparametric, and empirical mode decomposition. Preclinical AD was assessed by longitudinal clinical assessment, amyloid imaging with PiB, and cerebrospinal fluid biomarker collection. Results: Data from 189 participants were included in the analyses. The mean (SD) age was 66.6 (8.3) years, and 121 participants (64%) were women. Older age (β = .247; P = .003) and male sex (β = .170; P = .04), in the absence of amyloid pathology, were associated with a significant increase in intradaily variability, a nonparametric measure of rest-activity rhythm fragmentation, as well as decreased amplitude by several measures. After correction for age and sex, the presence of preclinical amyloid plaque pathology, assessed by positive PiB imaging (mean [SD], 0.804 [0.187] for PiB negative vs 0.875 [0.178] for PiB positive; P = .05) or increasing cerebrospinal fluid phosphorylated-tau to amyloid β 42 ratio (β = .231; P = .008), was associated with increased intradaily variability, indicating rest-activity rhythm fragmentation. Conclusions and Relevance: Preclinical AD is associated with rest-activity rhythm fragmentation, independent of age or sex. Aging was also associated with circadian dysfunction independently of preclinical AD pathology, particularly in men. The presence of circadian rhythm abnormalities in the preclinical phase of AD suggests that circadian dysfunction could contribute to early disease pathogenesis or serve as a biomarker of preclinical disease.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“There is also some evidence of an association of Aβ accumulation with disruption of the circadian rhythm and sleep pattern in cognitively normal adults.(321)”
From Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission (2024) · cites this paper as [321]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The Clinical Dementia Rating (CDR): Current version and scoring rules
Morris, J. C. (1993) · Neurology · doi:10.1212/wnl.43.11.2412-a · Cited by 9,882
Self-citationSperling, R. A., Aisen, P. S., Beckett, L. A., Bennett, D. A., Craft, S., Fagan, A. M., Iwatsubo, T., Jack, C. R., Kaye, J., Montine, T. J., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.003 · Cited by 7,155
Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade
Jack, C. R., Knopman, D. S., Jagust, W. J., Shaw, L. M., Aisen, P. S., Weiner, M. W., Petersen, R. C., & Trojanowski, J. Q. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70299-6 · Cited by 4,806
Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound‐B
Klunk, W. E., Engler, H., Nordberg, A., Wang, Y., Blomqvist, G., Holt, D. P., Bergström, M., Savitcheva, I., Huang, G., Estrada, S., et al. (2004) · Annals of Neurology · doi:10.1002/ana.20009 · Cited by 4,496
Villemagne, V. L., Burnham, S., Bourgeat, P., Brown, B., Ellis, K. A., Salvado, O., Szoeke, C., Macaulay, S. L., Martins, R., Maruff, P., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70044-9 · Cited by 2,279
Central and Peripheral Circadian Clocks in Mammals
Mohawk, J. A., Green, C. B., & Takahashi, J. S. (2012) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-060909-153128 · Cited by 2,265
Circadian integration of metabolism and energetics
Bass, J., & Takahashi, J. S. (2010) · Science · doi:10.1126/science.1195027 · Cited by 1,910
Prevalence of Cerebral Amyloid Pathology in Persons Without Dementia: A Meta-analysis
Jansen, W. J., Ossenkoppele, R., Knol, D. L., Tijms, B. M., Scheltens, P., Verhey, F. R. J., Visser, P. J., Aalten, P., Aarsland, D., Alcolea, D., et al. (2015) · JAMA · doi:10.1001/jama.2015.4668 · Cited by 1,610
Self-citationAmyloid-β Dynamics Are Regulated by Orexin and the Sleep-Wake Cycle
Kang, J.-E., Lim, M. M., Bateman, R. J., Lee, J. J., Smyth, L. P., Cirrito, J. R., Fujiki, N., Nishino, S., & Holtzman, D. M. (2009) · Science · doi:10.1126/science.1180962 · Cited by 1,565
Self-citationSleep and Alzheimer disease pathology--a bidirectional relationship
Ju, Y.-E. S., Lucey, B. P., & Holtzman, D. M. (2014) · Nature Reviews Neurology · doi:10.1038/nrneurol.2013.269 · Cited by 996
Self-citation
Research works printed but not linked: 2
- [20]20. Peter-Derex L, Yammine P, Bastuji H, Croisile B. Sleep and Alzheimer's disease. Sleep Med Rev. 2015; 19:29-38.
- [55]55. La Morgia C, Ross-Cisneros FN, Koronyo Y, et al. Melanopsin retinal ganglion cell loss in Alzheimer disease. Ann Neurol. 2016;79(1):90-109.
Cited by
Sorted by citations
Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission
Livingston, G., Huntley, J., Liu, K. Y., Costafreda, S. G., Selbæk, G., Alladi, S., Ames, D., Banerjee, S., Burns, A., Brayne, C., et al. (2024) · The Lancet · doi:10.1016/s0140-6736(24)01296-0 · Cited by 3,860
Association between circadian rhythms and neurodegenerative diseases
Leng, Y., Musiek, E. S., Hu, K., Cappuccio, F. P., & Yaffe, K. S. (2019) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30461-7 · Cited by 677
Self-citationAssociation of sleep duration in middle and old age with incidence of dementia
Sabia, S., Fayosse, A., Dumurgier, J., van Hees, V. T., Paquet, C., Sommerlad, A., Kivimäki, M., Dugravot, A., & Singh-Manoux, A. (2021) · Nature Communications · doi:10.1038/s41467-021-22354-2 · Cited by 628
Genomics of circadian rhythms in health and disease
Rijo‐Ferreira, F., & Takahashi, J. S. (2019) · Genome Medicine · doi:10.1186/s13073-019-0704-0 · Cited by 555
Alzheimer’s disease: insights into pathology, molecular mechanisms, and therapy
Zheng, Q., & Wang, X. (2024) · Protein & Cell · doi:10.1093/procel/pwae026 · Cited by 483
Metadata
- Authors
- Musiek, E. S., Bhimasani, M., Zangrilli, M. A., Morris, J. C., Holtzman, D. M., & Ju, Y.-E. S.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Ju, Yo-El S.
- Venue
- JAMA Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2018-05-01
- Volume
- 75
- Issue
- 5
- Pages
- 582
- ISSN
- 2168-6149 (ISSN-L)
- PMC
- PMC5885197
- OpenAlex
- W2792021696
- Cited by
- 465
- References
- 70
- Citations by year
- 2026: 59 · 2025: 75 · 2024: 64 · 2023: 52 · 2022: 50 · 2021: 58 · 2020: 57 · 2019: 32 · 2018: 18
- FWCI
- 23.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (KL2TR000450, UL1TR002345, KL2TR002346)
- National Institute on Aging (P50AG005681, P01AG003991, P01AG026276)
- National Institute of Neurological Disorders and Stroke (K23NS089922, K08NS079405, P01NS074969)
- National Center for Research Resources (UL1RR024992)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Keywords
- circadian rhythm, preclinical Alzheimer's disease, aging, actigraphy, intradaily variability, Pittsburgh compound B, amyloid-beta 42, circadian dysfunction, sex differences, cognitive aging, empirical mode decomposition, cosinor analysis, nonparametric statistics, sleep-wake cycle
- MeSH terms
- Aged, Aging, Alzheimer Disease, Aniline Compounds, Cross-Sectional Studies, Female, Humans, Longitudinal Studies, Male, Middle Aged, Peptide Fragments, Thiazoles, Amyloid beta-Peptides, tau Proteins, Statistics, Nonparametric, Chronobiology Disorders, Positron-Emission Tomography, Actigraphy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
