Low circulating adropin concentrations predict increased risk of cognitive decline in community-dwelling older adults
Open accessPublished version of a preprint
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 = 4.5 years, 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 (∆CCS) 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 ∆CCS 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, ∆CCS was significantly different ( P = 0.01; estimated marginal mean ± SE for the 1st to 3rd tertile, − 0.317 ± 0.064; − 0.275 ± 0.063; − 0.042 ± 0.071; n = 133,146, and 130, respectively; P < 0.05 for 1st vs. 2nd and 3rd adropin tertiles). Normalized plasma Aß 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.
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Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease
Jack, C. R., Bennett, D. A., Blennow, K., Carrillo, M. C., Dunn, B., Haeberlein, S. B., Holtzman, D. M., Jagust, W., Jessen, F., Karlawish, J., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.02.018 · Cited by 10,537 · see citing works
2023 Alzheimer's disease facts and figures
(2023) · Alzheimer's & Dementia · doi:10.1002/alz.13016 · Cited by 3,212 · see citing works
The Critical Role of Metabolic Pathways in Aging
Barzilai, N., Huffman, D. M., Muzumdar, R. H., & Bartke, A. (2012) · Diabetes · doi:10.2337/db11-1300 · Cited by 803 · see citing works
Adropin: A hepatokine modulator of vascular function and cardiac fuel metabolism
Mushala, B. A. S., & Scott, I. (2021) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00449.2020 · Cited by 53 · see citing works
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Bridging neurotrophic factors and bioactive peptides to Alzheimer’s disease
Wei, M., Wu, T., & Chen, N. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102177 · Cited by 31 · see citing works
- Authors
- Aggarwal, G., Morley, J. E., Vellas, B., Nguyen, A. D., Butler, A. A., for the MAPT/DSA Group, Guyonnet, S., Carrié, I., Brigitte, L., Faisant, C., Lala, F., Delrieu, J., Villars, H., Combrouze, E., Badufle, C., Zueras, A., Andrieu, S., Cantet, C., Morin, C., Van Kan, G. A., Dupuy, C., Rolland, Y., Caillaud, C., Ousset, P.-J., Lala, F., Willis, S., Belleville, S., Gilbert, B., Fontaine, F., Dartigues, J.-F., Marcet, I., Delva, F., Foubert, A., Cerda, S., Marie-Noëlle-Cuffi, Costes, C., Rouaud, O., Manckoundia, P., Quipourt, V., Marilier, S., Franon, E., Bories, L., Pader, M.-L., Basset, M.-F., Lapoujade, B., Faure, V., Tong, M. L. Y., Malick-Loiseau, C., Cazaban-Campistron, E., Desclaux, F., Blatge, C., Dantoine, T., Laubarie-Mouret, C., Saulnier, I., Clément, J.-P., Picat, M.-A., Bernard-Bourzeix, L., Willebois, S., Désormais, I., Cardinaud, N., Bonnefoy, M., Livet, P., Rebaudet, P., Gédéon, C., Burdet, C., Terracol, F., Pesce, A., Roth, S., Chaillou, S., Louchart, S., Sudres, K., Lebrun, N., Barro-Belaygues, N., Touchon, J., Bennys, K., Gabelle, A., Romano, A., Touati, L., Marelli, C., Pays, C., Robert, P., Le Duff, F., Gervais, C., Gonfrier, S., Gasnier, Y., Bordes, S., Begorre, D., Carpuat, C., Khales, K., Lefebvre, J.-F., El Idrissi, S. M., Skolil, P., Salles, J.-P., Dufouil, C., Lehéricy, S., Chupin, M., Mangin, J.-F., Bouhayia, A., Allard, M., Ricolfi, F., Dubois, D., Martel, M. P. B., Cotton, F., Bonafé, A., Chanalet, S., Hugon, F., Bonneville, F., Cognard, C., Chollet, F., Payoux, P., Voisin, T., Delrieu, J., Peiffer, S., Hitzel, A., Allard, M., Zanca, M., Monteil, J., Darcourt, J., Molinier, L., Derumeaux, H., Costa, N., Perret, B., Vinel, C., Caspar-Bauguil, S., Olivier-Abbal, P., Andrieu, S., Cantet, C., & Coley, N.
- Affiliations
- Washington University in St. Louis (US)
- Centre Hospitalier Universitaire de Toulouse (FR)
- The University of Western Australia (AU)
- Centre d'Epidémiologie et de Recherche en santé des POPulations de Toulouse (FR)
- Centre Européen de la Céramique (FR)
- Institut Universitaire de Gériatrie de Montréal (CA)
- Université de Bordeaux (FR)
- Laboratoire de Génie des Procédés – Environnement – Agro-alimentaire (FR)
- CHU Dijon Bourgogne (FR)
- Corresponding author
- Nguyen, Andrew D.
- Butler, Andrew A.
- ORCID
- Aggarwal, Geetika
- Morley, John E.
- Vellas, Bruno
- Nguyen, Andrew D.
- Butler, Andrew A.
- Guyonnet, Sophie
- Villars, Hélène
- Rolland, Yves
- Ousset, Pierre-Jean
- Willis, Sherry
- Belleville, Sylvie
- Gilbert, Brigitte
- Dartigues, Jean-François
- Delva, Fleur
- Rouaud, Olivier
- Manckoundia, Patrick
- Quipourt, Valérie
- Faure, Valérie
- Clément, Jean-Pierre
- Bonnefoy, Marc
- Pesce, Alain
- Louchart, Sandrine
- Bennys, Karim
- Gabelle, Audrey
- Marelli, Cécilia
- Robert, Philippe
- Dufouil, Carole
- Lehéricy, Stéphane
- Mangin, Jean-François
- Ricolfi, Frédéric
- Martel, Marie Paule Bonceour
- Cotton, François
- Bonafé, Alain
- Bonneville, Fabrice
- Cognard, Christophe
- Chollet, François
- Payoux, Pierre
- Monteil, Jacques
- Darcourt, Jacques
- Molinier, Laurent
- Costa, Nadège
- Perret, Bertrand
- Vinel, Claire
- Coley, Nicola
- Venue
- GeroScience
- Published
- 2023-05-26
- Volume
- 46
- Issue
- 1
- Pages
- 897-911
- ISSN
- 2152-4041 (ISSN-L)
- 2509-2723
- PMC
- PMC10828274
- OpenAlex
- W4378347872
- Cited by
- 13
- References
- 5
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 3 · 2023: 2
- FWCI
- 2.65
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- 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
- Gérontopôle of Toulouse
- French Ministry of Health
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Epidemiology › 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
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