Memory Self-Awareness Phenotypes are Associated with Alzheimer’s Disease Biomarker Burden and Clinical Progression in Amnestic Mild Cognitive Impairment
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Background
Altered memory self-awareness is common in mild cognitive impairment (MCI), but its relationship to Alzheimer’s disease (AD) pathology and progression remains unclear.
Methods
Using 590 amnestic MCI ADNI participants, memory self-awareness was derived from participant–informant discrepancies on the memory subdomain of the Everyday Cognition questionnaire. Heightened awareness and unawareness subscores were calculated, and k-means clustering identified four phenotypes. Associations with cerebrospinal fluid (CSF) and positron emission tomography (PET) were examined, and clinical progression was assessed using Cox models.
Results
Aware and Unaware groups showed lower CSF amyloid-β, and higher CSF phosphorylated tau and PET amyloid. The Unaware phenotype was associated with increased progression risk (hazard ratio 2.41, 95% CI 1.48–3.92), whereas the Worried Well phenotype showed reduced risk (hazard ratio 0.58, 95% CI 0.34–0.99).
Conclusions
Multidimensional assessment of memory self-awareness identifies biologically and prognostically distinct subgroups within MCI and may improve risk stratification in prodromal AD.
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Memory Self-Awareness Phenotypes are Associated with Alzheimers Disease Biomarker Burden and Clinical Progression in Amnestic Mild Cognitive Impairment #NeuroDegeneration 🧪🧠 https://www.medrxiv.org/content/10.64898/2026.11.03.26367187v1
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