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Clinical Manifestations.

David Facal1,2,3, Ana I Rodríguez-Pérez3,4,5, Fátima Fernández-Feijoo1,2

  • 1Instituto de Psicoloxía (IPsiUS), Universidade de Santiago de Compostela, Santiago de Compostela, Galicia, Spain.

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

Cognitive frailty (CF) is linked to plasma Alzheimer's disease (AD) markers, with higher levels found in potentially reversible cognitive pre-frailty (PRCPF) compared to physical pre-frailty (PPF) without cognitive decline. This suggests cognitive status is more influential than functional status in relation to these biomarkers.

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Area of Science:

  • Gerontology
  • Neuroscience
  • Biomarkers

Background:

  • Cognitive frailty (CF) involves co-occurring physical frailty and cognitive impairment, excluding dementia.
  • CF is potentially reversible, especially with physical pre-frailty (PPF) and Subjective Cognitive Decline (SCD).
  • While neuroimaging links to CF exist, plasma Alzheimer's disease (AD) biomarkers like NfL, Ab42, Ab40, t-Tau, p-tau181, and p-tau217 are less studied in this context.

Purpose of the Study:

  • To investigate the relationship between plasma AD biomarkers and cognitive frailty (CF) status.
  • To compare levels of specific plasma AD biomarkers across different frailty and cognitive states.
  • To explore whether cognitive or functional status is more strongly associated with plasma AD biomarkers in individuals at risk for CF.

Main Methods:

  • Analyzed plasma samples from 325 participants using ultra-sensitive Single Molecule Array (SIMOA) technology.
  • Quantified concentrations of NfL, Aβ-40, Aβ-42, tau, p-tau217, and p-tau181.
  • Compared biomarker levels between non-frail, PPF without cognitive decline, RCPF, and PRCPF groups.

Main Results:

  • Significant differences in NfL and p-Tau217 levels were observed between groups.
  • Lower NfL and p-Tau217 levels were found in the PPF without cognitive decline group compared to the PRCPF group.
  • These findings suggest a link between specific plasma AD biomarkers and cognitive status within frailty spectrum.

Conclusions:

  • Plasma AD biomarker levels appear more closely related to participants' cognitive status than their functional status.
  • Further research using regression models is needed to confirm CF status as a dependent variable with plasma AD biomarkers and functional markers as predictors.
  • This study highlights the potential role of plasma biomarkers in understanding and potentially managing cognitive frailty.