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Plasma levels of neurology-related proteins are associated with cognitive performance in an older population with overweight/obesity and metabolic syndrome

Llaurador-Coll, Martí, Rios, Santiago, García-Gavilán, Jesus F., Babio, Nancy, Vilella, Elisabet, Salas-Salvadó, Jordi·2023·GeroScience
DOI 10.1007/s11357-023-00764-yPMC PMC10651568
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Abstract

Cognitive impairment is present in a broad spectrum of medical conditions and in aging. Here, we aimed to identify plasma proteins related to cognitive function in a sample of older adults with overweight/obesity and metabolic syndrome. A total of 129 subjects (mean age 64.7 years; 36% females) were grouped according to low (l-GCF, N=65) or high (h-GCF, N=64) global cognitive function and matched according to education, sex, age, and body mass index. Cognitive performance was assessed using neuropsychological tests. Plasma levels of 92 neurology-related proteins were assessed using a proximity extension assay. An elastic net regression analysis was used to identify proteins more associated with cognitive performance. Additionally, the protein expression levels were compared between the two groups by means of a t-test with false discovery rate correction. Pearson correlations were used to assess associations between the protein levels and scores from the neurocognitive tests. Six proteins (alpha-2-MRAP, HAGH, Siglec-9, MDGA1, IL12, and EDA2R) were identified as potential contributors to cognitive performance, remaining significantly increased in l-GCF compared to h-GCF participants after correction for multiple testing. Negative correlations (r= −0.23 to −0.18, i.e., lower protein levels, higher cognitive function) were found between global cognitive function and Siglec-9, NMNAT1, HAGH, LXN, gal-8, alpha-2-MRAP, IL12, PDGF-R-alpha, NAAA, EDA2R, CLEC1B, and LAT. Mini-mental state examination z scores showed the strongest correlations with protein levels, specifically negative correlations with CLEC1b, LXN, LAT, PLXNB3, NMNAT1, gal-8, HAGH, NAAA, CTSS, EZR, KYNU, MANF (r=−0.38 to −0.26) and a positive correlation with ADAM23 (r= 0.26). In summary, we identified several plasma proteins that were significantly associated with cognitive performance in older adults with obesity and metabolic syndrome, although further research is needed to replicate the results in larger samples and to include a predictive perspective.

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Metadata

Authors
Llaurador-Coll, M., Rios, S., García-Gavilán, J. F., Babio, N., Vilella, E., & Salas-Salvadó, J.
ORCID
Venue
GeroScience
Publisher
Springer Science and Business Media LLC
Published
2023-03-25
Volume
45
Issue
4
Pages
2457-2470
ISSN
2509-2723
DOI
10.1007/s11357-023-00764-y
PMC
PMC10651568
Cited by
21
References
7
Language
en
Licence
Funders
  • Agència de Gestió d'Ajuts Universitaris i de Recerca (2017SGR444, 2017SGR691)
  • “la Caixa” Foundation (2013ACUP00194)
  • Universitat Rovira i Virgili (PMF2021-IN000681)
  • Instituto de Salud Carlos III (PI13/00462, PI16/00501, PI19/00576)

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