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Clinical Manifestations.

David López-Martos1,2, Raffaele Cacciaglia1,3,4, Marc Suárez-Calvet1,5,6

  • 1Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
PubMed
Summary

Anosognosia, or lack of awareness of impairment, is linked to Alzheimer's disease (AD) biomarkers and brain changes even before mild cognitive impairment (MCI). Early detection of anosognosia is crucial for timely intervention in individuals at risk for AD dementia.

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Area of Science:

  • Neuroscience
  • Neurology
  • Biomarkers

Background:

  • Anosognosia (lack of awareness of impairment) is common in Alzheimer's disease (AD) but not recognized in Mild Cognitive Impairment (MCI) criteria.
  • Subjective Cognitive Decline (SCD) is used instead, but it's not specific to AD and may be absent in MCI.
  • The neuropathological basis of anosognosia and its role in early AD stages remain unclear.

Purpose of the Study:

  • To investigate the longitudinal relationship between multimodal AD biomarkers and meta-cognitive changes.
  • To examine these associations in cognitively unimpaired (CU) individuals at risk for AD dementia.

Main Methods:

  • 331 CU participants with early AD biomarker profiles were studied.
  • Baseline CSF and plasma biomarkers, 3-year longitudinal MRI, and neuropsychological tests were used.
  • Meta-memory trajectory was calculated as the discrepancy between objective and subjective cognitive performance.

Main Results:

  • Meta-memory decline correlated with lower CSF Aβ42/40 and higher CSF p-tau181/Aβ42.
  • Plasma p-tau217 and plasma GFAP were also associated with meta-memory decline.
  • Decline in meta-memory was linked to increased grey matter volume in frontal cortex, insula, and other brain regions.

Conclusions:

  • Anosognosia trajectory is associated with AD pathophysiology and brain structural changes in pre-MCI stages.
  • Early detection of anosognosia is vital, as current criteria may overlook it.
  • Identifying at-risk individuals is critical for implementing objective diagnostics and prevention strategies for AD.