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Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies
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Biomarkers.

Longjian Liu1, Jintong Hou1, Yvonne L Michael2

  • 1Drexel University Dornsife School of Public Health, Philadelphia, PA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
PubMed
Summary
This summary is machine-generated.

Cardio-kidney-metabolic (CKM) phenotypic age is linked to cognitive decline, especially with the APOE e4 genotype. This biological aging indicator offers new strategies for preventing cognitive impairment.

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Area of Science:

  • Gerontology
  • Neuroscience
  • Metabolic Syndrome Research

Background:

  • The relationship between cardio-kidney-metabolic (CKM) syndrome, cognitive decline, and APOE genotype is not well understood.
  • Investigating CKM phenotypic age (CKMAge) and its association with cognitive decline is crucial.

Purpose of the Study:

  • To examine the association between CKMAge and cognitive decline in U.S. adults.
  • To explore the modifying effect of Apolipoprotein E (APOE) genotype on this association.

Main Methods:

  • Analysis of 13,222 U.S. adults (≥50 years) from the Health and Retirement Study.
  • Development of CKMAge using hypertension, systolic BP, Cystatin C, hemoglobin A1c, and chronological age.
  • Assessment of cognitive function and APOE genotyping; logistic regression and AUC-ROC analyses were performed.

Main Results:

  • Higher CKMAge quantiles showed a significantly increased rate of cognitive decline (p < 0.001).
  • Each 5-year increase in CKMAge raised cognitive decline risk by 21% (OR: 1.21).
  • CKMAge and APOE e4 interacted significantly, improving classification accuracy to 72.1% when combined.

Conclusions:

  • CKM phenotypic age is a significant contributor to cognitive decline, independent of APOE e4.
  • Findings suggest novel therapeutic and preventive strategies for cognitive impairment by targeting CKM age.