Frontiers in Aging Neuroscience (Apr 2024)

Association of multiple metabolic and cardiovascular markers with the risk of cognitive decline and mortality in adults with Alzheimer’s disease and AD-related dementia or cognitive decline: a prospective cohort study

  • Longjian Liu,
  • Edward J. Gracely,
  • Edward J. Gracely,
  • Xiaopeng Zhao,
  • Gediminas P. Gliebus,
  • Nathalie S. May,
  • Stella L. Volpe,
  • Jingyi Shi,
  • Rose Ann DiMaria-Ghalili,
  • Howard J. Eisen

DOI
https://doi.org/10.3389/fnagi.2024.1361772
Journal volume & issue
Vol. 16

Abstract

Read online

Background and objectivesThere is a scarcity of data stemming from large-scale epidemiological longitudinal studies focusing on potentially preventable and controllable risk factors for Alzheimer’s disease (AD) and AD-related dementia (ADRD). This study aimed to examine the effect of multiple metabolic factors and cardiovascular disorders on the risk of cognitive decline and AD/ADRD.MethodsWe analyzed a cohort of 6,440 participants aged 45–84 years at baseline. Multiple metabolic and cardiovascular disorder factors included the five components of the metabolic syndrome [waist circumference, high blood pressure (HBP), elevated glucose and triglyceride (TG) concentrations, and reduced high-density lipoprotein cholesterol (HDL-C) concentrations], C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), factor VIII, D-dimer, and homocysteine concentrations, carotid intimal-medial thickness (CIMT), and urine albumin-to-creatinine ratio (ACR). Cognitive decline was defined using the Cognitive Abilities Screening Instrument (CASI) score, and AD/ADRD cases were classified using clinical diagnoses.ResultsOver an average follow-up period of 13 years, HBP and elevated glucose, CRP, homocysteine, IL-6, and ACR concentrations were significantly associated with the risk of mortality in the individuals with incident AD/ADRD or cognitive decline. Elevated D-dimer and homocysteine concentrations, as well as elevated ACR were significantly associated with incident AD/ADRD. Elevated homocysteine and ACR were significantly associated with cognitive decline. A dose–response association was observed, indicating that an increased number of exposures to multiple risk factors corresponded to a higher risk of mortality in individuals with cognitive decline or with AD/ADRD.ConclusionFindings from our study reaffirm the significance of preventable and controllable factors, including HBP, hyperglycemia, elevated CRP, D-dimer, and homocysteine concentrations, as well as, ACR, as potential risk factors for cognitive decline and AD/ADRD.

Keywords