CoChat
Sign Up
PreprintCited by 13Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsAdipokines, Inflammation, and Metabolic Diseases

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

Low circulating adropin concentrations predict increased risk of cognitive decline in community-dwelling older adults

Open access
Aggarwal, Geetika, Morley, John E., Vellas, Bruno, Nguyen, Andrew D., Butler, Andrew A., the MAPT/DSA Group·2023·GeroScience
DOI 10.1101/2023.03.24.23285476PMC PMC10828274

Preprint — published as 10.1007/s11357-023-00824-3 · Paper page

Open this paper in CoChat — free accountOpen PDF

Abstract

The secreted peptide adropin is highly expressed in human brain tissues and correlates with RNA and proteomic risk indicators for dementia. Here we report that plasma adropin concentrations predict risk for cognitive decline in the Multidomain Alzheimer Preventive Trial ( ClinicalTrials.gov Identifier, NCT00672685 ; mean age 75.8y, SD=4.5y, 60.2% female, n=452). Cognitive ability was evaluated using a composite cognitive score (CCS) that assessed four domains: memory, language, executive function, and orientation. Relationships between plasma adropin concentrations and changes in CCS (ΔCCS) were examined using Cox Proportional Hazards Regression, or by grouping into tertiles ranked low to high by adropin values and controlling for age, time between baseline and final visits, baseline CCS, and other risk factors (e.g., education, medication, APOE4 status). Risk of cognitive decline (defined as a ΔCCS of -0.3 or more) decreased with increasing plasma adropin concentrations (hazard ratio = 0.873, 95%CI 0.780-0.977, P=0.018). Between adropin tertiles, ΔCCS was significantly different (P=0.01; estimated marginal mean±SE for the 1 st -to 3 rd -tertile, -0.317±0.064; -0.275±0.063; -0.042±0.071; n=133,146, and 130, respectively; P<0.05 for 1 st vs. 2 nd and 3 rd adropin tertiles). Normalized plasma Aβ 42/40 ratio and plasma neurofilament light chain, indicators of neurodegeneration, were significantly different between adropin tertile. These differences were consistent with reduced risk of cognitive decline with higher plasma adropin levels. Overall, these results suggest cognitive decline is reduced in community-dwelling older adults with higher circulating adropin levels. Further studies are needed to determine the underlying causes of the relationship and whether increasing adropin levels can delay cognitive decline.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1101/2023.03.24.23285476

Cites

3 of 3 references verified0 citation errors · 0 not checkable

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.

A few free checks a day · papers already verified open instantly · results are public

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

Flagged first, then by citations

Research works printed but not linked: 45

  1. 10.1038/nature06516 · DOI
  2. 10.1016/S2468-2667(21)00249-8 · DOI · Paper page
  3. 10.1016/S1474-4422(21)00361-6 · DOI · Paper page
  4. 2023, The multifaceted role of neurofilament light chain protein in non-primary neurological diseases, Brain, 146, 421, 10.1093/brain/awac328 · DOI
  5. 2022, The performance of plasma amyloid beta measurements in identifying amyloid plaques in Alzheimer’s disease: a literature review, Alzheimers Res Ther, 14, 195, 10.1186/s13195-022-01117-1 · DOI · Paper page
  6. 2023, Impacts of FDA approval and Medicare restriction on antiamyloid therapies for Alzheimer’s disease: patient outcomes, healthcare costs, and drug development, Lancet Reg Health Am, 20, 100467
  7. 10.1016/j.cmet.2008.10.011 · DOI
  8. 10.1074/jbc.M114.576058 · DOI
  9. 10.1093/bioinformatics/17.9.849 · DOI
  10. 10.1002/oby.23249 · DOI
  11. 10.1152/ajpheart.00449.2020 · DOI · Paper page
  12. 10.2337/db11-1300 · DOI · Paper page
  13. 10.1074/jbc.RA119.008967 · DOI
  14. 10.1074/jbc.RA120.014381 · DOI
  15. 10.14814/phy2.14043 · DOI
  16. 2015, Therapeutic effects of adropin on glucose tolerance and substrate utilization in diet-induced obese mice with insulin resistance, Mol Metab, 4, 310, 10.1016/j.molmet.2015.01.005 · DOI
  17. Chen X , Chen S , Shen T , Yang W , Chen Q , Zhang P , et al. Adropin regulates hepatic glucose production via PP2A/AMPK pathway in insulin-resistant hepatocytes. FASEB J. 2020. · DOI
  18. 10.2337/db14-0388 · DOI
  19. 10.1016/j.metabol.2019.06.005 · DOI
  20. 10.1152/ajpheart.00385.2022 · DOI
  21. Fujie S , Hasegawa N , Horii N , Uchida M , Sanada K , Hamaoka T , et al. Aerobic Exercise Restores Aging-Associated Reductions in Arterial Adropin Levels and Improves Adropin-Induced Nitric Oxide-Dependent Vasorelaxation. J Am Heart Assoc. 2021:e020641. · DOI
  22. 2017, Association between aerobic exercise training effects of serum adropin level, arterial stiffness, and adiposity in obese elderly adults, Appl Physiol Nutr Metab, 42, 8, 10.1139/apnm-2016-0310 · DOI
  23. 10.1152/ajpheart.00338.2015 · DOI
  24. 2023, Protective roles of adropin in neurological disease, Am J Physiol Cell Physiol, 324, C674, 10.1152/ajpcell.00318.2022 · DOI
  25. 2023, Therapeutic Benefits of Adropin in Aged Mice After Transient Ischemic Stroke via Reduction of Blood-Brain Barrier Damage, Stroke, 54, 234, 10.1161/STROKEAHA.122.039628 · DOI
  26. 2021, Neurovascular protection by adropin in experimental ischemic stroke through an endothelial nitric oxide synthase-dependent mechanism, Redox Biol, 48, 102197, 10.1016/j.redox.2021.102197 · DOI
  27. 2021, Adropin correlates with aging-related neuropathology in humans and improves cognitive function in aging mice, NPJ Aging Mech Dis, 7, 23, 10.1038/s41514-021-00076-5 · DOI
  28. 10.1074/jbc.RA119.007528 · DOI
  29. 10.14336/AD.2017.0523 · DOI
  30. 10.1016/j.peptides.2021.170678 · DOI
  31. 2014, Mapt Study: A Multidomain Approach for Preventing Alzheimer’s Disease: Design and Baseline Data, J Prev Alzheimers Dis, 1, 13
  32. 10.1016/S1474-4422(17)30040-6 · DOI · Paper page
  33. 2020, Plasma Abeta and neurofilament light chain are associated with cognitive and physical function decline in non-dementia older adults, Alzheimers Res Ther, 12, 128, 10.1186/s13195-020-00697-0 · DOI
  34. 2021, Prospective Associations between Plasma Amyloid-Beta 42/40 and Frailty in Community-Dwelling Older Adults, J Prev Alzheimers Dis, 8, 41
  35. 2020, Assessment of Plasma Amyloid-beta42/40 and Cognitive Decline Among Community-Dwelling Older Adults, JAMA Netw Open, 3, e2028634, 10.1001/jamanetworkopen.2020.28634 · DOI
  36. 2016, Evaluating the clinical relevance of a cognitive composite outcome measure: An analysis of 1414 participants from the 5-year GuidAge Alzheimer’s prevention trial, Alzheimers Dement, 12, 1216, 10.1016/j.jalz.2016.06.002 · DOI
  37. 2022, Alzheimer’s risk variant APOE4 linked to myelin-assembly malfunction, Nature, 611, 670, 10.1038/d41586-022-03371-7 · DOI
  38. 2022, This is how an Alzheimer’s gene ravages the brain, Nature, 611, 649, 10.1038/d41586-022-03724-2 · DOI
  39. 2023, Plasma inflammation-related biomarkers are associated with intrinsic capacity in community-dwelling older adults, J Cachexia Sarcopenia Muscle, 14, 930, 10.1002/jcsm.13163 · DOI
  40. 2022, Physiological Bases for the Superiority of Apolipoprotein B Over Low-Density Lipoprotein Cholesterol and Non-High-Density Lipoprotein Cholesterol as a Marker of Cardiovascular Risk, J Am Heart Assoc, 11, e025858, 10.1161/JAHA.122.025858 · DOI
  41. 2021, Healthy aging and the blood-brain barrier, Nat Aging, 1, 243, 10.1038/s43587-021-00043-5 · DOI
  42. 2021, Blood-Brain Barrier Dynamics to Maintain Brain Homeostasis, Trends Neurosci, 44, 393, 10.1016/j.tins.2020.12.002 · DOI
  43. 2018, Adropin: An endocrine link between the biological clock and cholesterol homeostasis, Mol Metab, 8, 51, 10.1016/j.molmet.2017.12.002 · DOI
  44. 2019, Adropin protects against liver injury in nonalcoholic steatohepatitis via the Nrf2 mediated antioxidant capacity, Redox Biol, 21, 101068, 10.1016/j.redox.2018.101068 · DOI
  45. 10.1038/srep14691 · DOI

Metadata

Authors
Aggarwal, G., Morley, J. E., Vellas, B., Nguyen, A. D., Butler, A. A., & the MAPT/DSA Group
Affiliations
  • Washington University in St. Louis (US)
  • Centre Hospitalier Universitaire de Toulouse (FR)
  • The University of Western Australia (AU)
Corresponding author
  • Nguyen, Andrew D.
  • Butler, Andrew A.
ORCID
Venue
GeroScience
Publisher
openRxiv
Published
2023-03-25
Volume
46
Issue
1
Pages
897-911
ISSN
2152-4041 (ISSN-L)
DOI
10.1101/2023.03.24.23285476
PMC
PMC10828274
OpenAlex
W4378347872
Cited by
13
References
3
Citations by year
2026: 3 · 2025: 5 · 2024: 3 · 2023: 2
FWCI
2.65
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • GeroScience (publishedVersion, other-oa)
  • medRxiv (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by)
  • Oskar-Bordeaux (Universite de Bordeaux) (submittedVersion, cc-by)
Funders
  • Saint Louis University
  • Les Laboratories Pierre Fabre
  • Institut National de la Santé et de la Recherche Médicale
  • Centre Hospitalier Universitaire de Toulouse
  • Avid Radiopharmaceuticals
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Keywords
adropin, cognitive decline, plasma biomarkers, dementia risk, community-dwelling older adults, Alzheimer's disease, amyloid-beta 42/40 ratio, neurofilament light chain, neurodegeneration
MeSH terms
Aged, Alzheimer Disease, Cognition, Female, Humans, Male, Proteomics, Independent Living, Cognitive Dysfunction

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