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Clinical Manifestations.

Alexandra J Weigand1, Fareshte Erani2, Caitlin M Terao3

  • 1Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Summary
This summary is machine-generated.

Cognitively healthy older adults show distinct cognitive patterns. Lower executive function links to cerebrovascular issues, while low memory may signal Alzheimer's disease risk via separate paths.

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Area of Science:

  • Neuroscience
  • Gerontology
  • Cognitive Psychology

Background:

  • Cognitively unimpaired (CU) older adults exhibit varied risks for Alzheimer's disease and related dementias (ADRD).
  • Identifying early cognitive phenotypes in CU individuals is crucial for timely interventions.
  • The Atherosclerosis Risk in Communities (ARIC) study provides a valuable cohort for examining cognitive heterogeneity.

Purpose of the Study:

  • To classify distinct cognitive phenotypes among CU older adults using a data-driven approach.
  • To investigate the association between identified cognitive phenotypes and ADRD/cerebrovascular outcomes.
  • To explore neuroimaging and biomarker differences across cognitive phenotypes.

Main Methods:

  • Latent profile analysis of 10 demographically adjusted neuropsychological z-scores from 4737 CU older adults in the ARIC study.
  • Comparison of phenotypes based on demographics, depressive symptoms, and vascular risk factors (VRFs).
  • Analysis of white matter hyperintensity (WMH), hippocampal volume (HV), and plasma biomarkers (Aβ42/40, ptau181, NfL, GFAP) in a subset.

Main Results:

  • A 6-class solution identified distinct cognitive phenotypes (e.g., Average Overall, Low Memory, Low Executive).
  • Phenotypes significantly differed in demographics, depressive symptoms, VRFs, WMH, HV, Aβ42/40, and ptau181.
  • Specific phenotypes showed associations: Low Executive with high WMH, Low Memory with low Aβ42/40 and high ptau181.

Conclusions:

  • Cognitive heterogeneity exists even in CU older adults, suggesting diverse risk trajectories.
  • Lower executive performance correlates with cerebrovascular changes.
  • Impaired memory is linked to AD-related biomarkers, indicating distinct pathways to cognitive decline.