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Accelerated Biological Aging, Neurodegenerative Disease, and Mortality in Cardiovascular Disease Patients: Mediation

Jinyue Li1,2, Han Ma3, Guohua Wang1,2

  • 1National Stroke Administration Office, Xuanwu Hospital Capital Medical University, Beijing, China.

CNS Neuroscience & Therapeutics
|July 29, 2026
PubMed

Insights

Accelerated biological aging, measured by Phenotypic age, is linked to higher risks of Alzheimer's, Parkinson's, and death in cardiovascular disease patients. Brain health conditions significantly mediate this association, suggesting personalized prevention strategies.

Area of Science:

  • Gerontology
  • Cardiology
  • Neurology

Background:

  • Cardiovascular disease (CVD) patients face elevated risks for neurodegenerative diseases and mortality, suggesting a common aging pathway affecting both heart and brain.
  • Phenotypic age (PhenoAge), a composite measure of biological aging, is a potential predictor, but its association with mortality and the mediating role of brain health in CVD patients are not well understood.

Purpose of the Study:

  • To investigate the association between Phenotypic age (PhenoAge) acceleration and the risks of Alzheimer's disease (AD), Parkinson's disease (PD), and all-cause mortality in patients with cardiovascular disease (CVD).
  • To determine the extent to which AD and PD mediate the relationship between PhenoAge and mortality in CVD patients.

Main Methods:

  • Analysis of 4104 cardiovascular disease (CVD) patients from the National Health and Nutrition Examination Survey with a median follow-up of 7.2 years.
  • Weighted regression models were used to assess the associations of Phenotypic age (PhenoAge) and its acceleration with Alzheimer's disease (AD), Parkinson's disease (PD), and mortality.
  • Mediation analyses quantified the role of AD and PD in the PhenoAge-mortality association.

Main Results:

  • Each 5-year increase in PhenoAge acceleration was independently associated with increased risks of AD (OR=1.24), PD (OR=1.22), and all-cause mortality (HR=1.30).
  • Alzheimer's disease (AD) and Parkinson's disease (PD) accounted for 20.46%-33.18% of the association between PhenoAge and mortality.
  • Early-onset CVD exacerbated biological aging-related mortality risk, while a healthy lifestyle mitigated this risk.

Conclusions:

  • Accelerated biological aging, as indicated by PhenoAge, is significantly associated with poorer brain health outcomes (AD, PD) and increased mortality in cardiovascular disease (CVD) patients.
  • AD and PD act as crucial mediators in the pathway linking accelerated aging to mortality in this population.
  • PhenoAge assessment can aid in identifying high-risk CVD individuals for targeted interventions aimed at preventing adverse heart-brain aging trajectories.
Abstract

Keywords:
biological agingcardiovascular disease patientsmortality riskneurodegenerative diseasessecondary prevention

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