Memory Self-Awareness Phenotypes are Associated with Alzheimers Disease Biomarker Burden and Clinical Progression in Amnestic Mild Cognitive Impairment
- 1Department of Neurology, Massachusetts General Hospital, Harvard Medical School. Department of Computer Science and Mathematics, Bowdoin College.
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-B, 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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BibTeX
@misc{enbarsalo2026memory,
title = {{Memory Self-Awareness Phenotypes are Associated with Alzheimers Disease Biomarker Burden and Clinical Progression in Amnestic Mild Cognitive Impairment}},
author = {N. Enbar-Salo and P. Palmer and C. Munro and M. A. Dubbelman and A. Aaronson and R. Nosheny and J. Gatchel and G. Marshall and P. Vannini and Alzheimer's Disease Neuroimaging Initiative},
howpublished = {medRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.03.26367187},
url = {https://www.medrxiv.org/content/10.64898/2026.11.03.26367187v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Memory Self-Awareness Phenotypes are Associated with Alzheimers Disease Biomarker Burden and Clinical Progression in Amnestic Mild Cognitive Impairment
AU - N. Enbar-Salo
AU - P. Palmer
AU - C. Munro
AU - M. A. Dubbelman
AU - A. Aaronson
AU - R. Nosheny
AU - J. Gatchel
AU - G. Marshall
AU - P. Vannini
AU - Alzheimer's Disease Neuroimaging Initiative
PY - 2026
DA - 2026/11/03
PB - medRxiv
DO - 10.64898/2026.11.03.26367187
UR - https://www.medrxiv.org/content/10.64898/2026.11.03.26367187v1
AB - 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-B, 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.
ER -