In-vivo MRI of noradrenergic and dopaminergic nuclei predicts future cognition and Alzheimers disease progression
- 1Leonard Davis School of Gerontology, University of Southern California
Abstract
Noradrenergic and dopaminergic nuclei modulate cognition, and post-mortem data indicate they are affected early in the neurodegenerative cascade of Alzheimers disease. We derived in-vivo locus coeruleus (LC) and substantia nigra-ventral tegmental area (SN-VTA) MRI integrity measures from 739 ADNI participants, examined MRI-histology correspondence in individuals with both in-vivo imaging and post-mortem data, and tested whether these measures reflect early MRI-indexed degeneration predicting later cognitive decline. LC and SN-VTA contrast predicted cognitive and behavioral function 10 years later, despite only weak associations with current function. LC- and SN-VTA-associated brain-wide atrophy patterns aligned with PET-derived norepinephrine-transporter and dopamine-receptor maps, respectively. A one-standard-deviation decrease in baseline LC contrast was associated with 84% higher five-year odds of MCI-to-AD progression, and predictive effects of the catecholaminergic nuclei were mediated by their corresponding atrophy patterns. The SN-VTA pattern was associated with less amyloid PET-related memory decline. Together, these findings establish LC and SN-VTA MRI contrast as markers of early neurodegeneration that forecast cognitive decline years before clinical onset.
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BibTeX
@misc{zhao2026invivo,
title = {{In-vivo MRI of noradrenergic and dopaminergic nuclei predicts future cognition and Alzheimers disease progression}},
author = {W. Zhao and S. J. Guzman and H. J. Yoo and K. Ruiz and K. Chen and A. Moheban and D. A. Nation and M. J. Dahl and M. Mather},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.29.762942},
url = {https://www.biorxiv.org/content/10.64898/2026.10.29.762942v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - In-vivo MRI of noradrenergic and dopaminergic nuclei predicts future cognition and Alzheimers disease progression
AU - W. Zhao
AU - S. J. Guzman
AU - H. J. Yoo
AU - K. Ruiz
AU - K. Chen
AU - A. Moheban
AU - D. A. Nation
AU - M. J. Dahl
AU - M. Mather
PY - 2026
DA - 2026/10/29
PB - bioRxiv
DO - 10.64898/2026.10.29.762942
UR - https://www.biorxiv.org/content/10.64898/2026.10.29.762942v1
AB - Noradrenergic and dopaminergic nuclei modulate cognition, and post-mortem data indicate they are affected early in the neurodegenerative cascade of Alzheimers disease. We derived in-vivo locus coeruleus (LC) and substantia nigra-ventral tegmental area (SN-VTA) MRI integrity measures from 739 ADNI participants, examined MRI-histology correspondence in individuals with both in-vivo imaging and post-mortem data, and tested whether these measures reflect early MRI-indexed degeneration predicting later cognitive decline. LC and SN-VTA contrast predicted cognitive and behavioral function 10 years later, despite only weak associations with current function. LC- and SN-VTA-associated brain-wide atrophy patterns aligned with PET-derived norepinephrine-transporter and dopamine-receptor maps, respectively. A one-standard-deviation decrease in baseline LC contrast was associated with 84% higher five-year odds of MCI-to-AD progression, and predictive effects of the catecholaminergic nuclei were mediated by their corresponding atrophy patterns. The SN-VTA pattern was associated with less amyloid PET-related memory decline. Together, these findings establish LC and SN-VTA MRI contrast as markers of early neurodegeneration that forecast cognitive decline years before clinical onset.
ER -