Frontiers in Endocrinology (Oct 2021)

Glycemic Dysregulations Are Associated With Worsening Cognitive Function in Older Participants at High Risk of Cardiovascular Disease: Two-Year Follow-up in the PREDIMED-Plus Study

  • Carlos Gómez-Martínez,
  • Carlos Gómez-Martínez,
  • Carlos Gómez-Martínez,
  • Nancy Babio,
  • Nancy Babio,
  • Nancy Babio,
  • Nancy Babio,
  • Jordi Júlvez,
  • Nerea Becerra-Tomás,
  • Nerea Becerra-Tomás,
  • Nerea Becerra-Tomás,
  • Miguel Á. Martínez-González,
  • Miguel Á. Martínez-González,
  • Miguel Á. Martínez-González,
  • Dolores Corella,
  • Dolores Corella,
  • Olga Castañer,
  • Olga Castañer,
  • Dora Romaguera,
  • Dora Romaguera,
  • Jesús Vioque,
  • Jesús Vioque,
  • Jesús Vioque,
  • Ángel M. Alonso-Gómez,
  • Ángel M. Alonso-Gómez,
  • Julia Wärnberg,
  • Julia Wärnberg,
  • José A. Martínez,
  • José A. Martínez,
  • José A. Martínez,
  • Luís Serra-Majem,
  • Luís Serra-Majem,
  • Ramón Estruch,
  • Ramón Estruch,
  • Francisco J. Tinahones,
  • Francisco J. Tinahones,
  • José Lapetra,
  • José Lapetra,
  • Xavier Pintó,
  • Xavier Pintó,
  • Xavier Pintó,
  • Josep A. Tur,
  • Josep A. Tur,
  • José López-Miranda,
  • José López-Miranda,
  • Aurora Bueno-Cavanillas,
  • Aurora Bueno-Cavanillas,
  • Aurora Bueno-Cavanillas,
  • José J. Gaforio,
  • José J. Gaforio,
  • Pilar Matía-Martín,
  • Lidia Daimiel,
  • Vicente Martín-Sánchez,
  • Vicente Martín-Sánchez,
  • Josep Vidal,
  • Josep Vidal,
  • Clotilde Vázquez,
  • Clotilde Vázquez,
  • Emilio Ros,
  • Emilio Ros,
  • Søren Dalsgaard,
  • Søren Dalsgaard,
  • Carmen Sayón-Orea,
  • José V. Sorlí,
  • José V. Sorlí,
  • Rafael de la Torre,
  • Rafael de la Torre,
  • Rafael de la Torre,
  • Itziar Abete,
  • Itziar Abete,
  • Lucas Tojal-Sierra,
  • Lucas Tojal-Sierra,
  • Francisco J. Barón-López,
  • Francisco J. Barón-López,
  • Noelia Fernández-Brufal,
  • Jadwiga Konieczna,
  • Jadwiga Konieczna,
  • Antonio García-Ríos,
  • Antonio García-Ríos,
  • Emilio Sacanella,
  • Emilio Sacanella,
  • M. Rosa Bernal-López,
  • M. Rosa Bernal-López,
  • José M. Santos-Lozano,
  • José M. Santos-Lozano,
  • Cristina Razquin,
  • Cristina Razquin,
  • Andrea Alvarez-Sala,
  • Andrea Alvarez-Sala,
  • Albert Goday,
  • Albert Goday,
  • M. Angeles Zulet,
  • M. Angeles Zulet,
  • Jessica Vaquero-Luna,
  • Jessica Vaquero-Luna,
  • Javier Diez-Espino,
  • Javier Diez-Espino,
  • Javier Diez-Espino,
  • Aida Cuenca-Royo,
  • Aida Cuenca-Royo,
  • Fernando Fernández-Aranda,
  • Fernando Fernández-Aranda,
  • Fernando Fernández-Aranda,
  • Mònica Bulló,
  • Mònica Bulló,
  • Mònica Bulló,
  • Jordi Salas-Salvadó,
  • Jordi Salas-Salvadó,
  • Jordi Salas-Salvadó,
  • Jordi Salas-Salvadó

DOI
https://doi.org/10.3389/fendo.2021.754347
Journal volume & issue
Vol. 12

Abstract

Read online

IntroductionType 2 diabetes has been linked to greater cognitive decline, but other glycemic parameters such as prediabetes, diabetes control and treatment, and HOMA-IR and HbA1c diabetes-related biomarkers have shown inconsistent results. Furthermore, there is limited research assessing these relationships in short-term studies. Thus, we aimed to examine 2-year associations between baseline diabetes/glycemic status and changes in cognitive function in older participants at high risk of cardiovascular disease.MethodsWe conducted a 2-year prospective cohort study (n=6,874) within the framework of the PREDIMED-Plus study. The participants (with overweight/obesity and metabolic syndrome; mean age 64.9 years; 48.5% women) completed a battery of 8 cognitive tests, and a global cognitive function Z-score (GCF) was estimated. At baseline, participants were categorized by diabetes status (no-diabetes, prediabetes, and <5 or ≥5-year diabetes duration), and also by diabetes control. Furthermore, insulin resistance (HOMA-IR) and glycated hemoglobin (HbA1c) levels were measured, and antidiabetic medications were recorded. Linear and logistic regression models, adjusted by potential confounders, were fitted to assess associations between glycemic status and changes in cognitive function.ResultsPrediabetes status was unrelated to cognitive decline. However, compared to participants without diabetes, those with ≥5-year diabetes duration had greater reductions in GCF (β=-0.11 (95%CI -0.16;-0.06)], as well as in processing speed and executive function measurements. Inverse associations were observed between baseline HOMA-IR and changes in GCF [β=-0.0094 (95%CI -0.0164;-0.0023)], but also between HbA1c levels and changes in GCF [β=-0.0085 (95%CI -0.0115, -0.0055)], the Mini-Mental State Examination, and other executive function tests. Poor diabetes control was inversely associated with phonologic fluency. The use of insulin treatment was inversely related to cognitive function as measured by the GCF [β=-0.31 (95%CI -0.44, -0.18)], and other cognitive tests.ConclusionsInsulin resistance, diabetes status, longer diabetes duration, poor glycemic control, and insulin treatment were associated with worsening cognitive function changes in the short term in a population at high cardiovascular risk.Clinical Trial Registrationhttp://www.isrctn.com/ISRCTN89898870, identifier ISRCTN: 89898870.

Keywords