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Memory Self-Awareness Phenotypes are Associated with Alzheimer’s Disease Biomarker Burden and Clinical Progression in Amnestic Mild Cognitive Impairment

Year: 2026
Type: preprint
Abstract: STRUCTURED ABSTRACT 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.
Source: medRxiv
DOI: 10.64898/2026.11.03.26367187
Authors: Nicholas Enbar-Salo, Phebe Palmer, Catherine Munro, Mark Dubbelman, Anna Aaronson, Rachel Nosheny, Jennifer Gatchel, Gad A. Marshall, Patrizia Vannini, the Alzheimer’s Disease Neuroimaging Initiative
Institutions: Bowdoin College, Harvard University, Massachusetts General Hospital, Brigham and Women's Hospital, Boston University, University of California, San Francisco, Northern California Institute for Research and Education, McLean Hospital
Language: English
Field: Medicine
Open Access status: green
OpenAlex ID: W7225325530
Cites: 46
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Related to: 10