Nucleus basalis of Meynert integrity is associated with cognitive dysfunction in Parkinson's disease independently of locus coeruleus degeneration
- 1University of Toronto
Abstract
BackgroundDegeneration in the cholinergic nucleus basalis of Meynert (nbM) is thought to contribute to early cognitive deficits in Parkinsons disease (PD). However, it is unknown whether this relationship is confounded by the parallel degeneration of the substantia nigra (SN) and the locus coeruleus (LC), and whether this relationship is unique to PD.
MethodsWe conducted a cross-sectional analysis in 112 PD patients (disease duration <10 years) and 46 controls who underwent standard neuropsychological testing, diffusion-weighted and neuromelanin magnetic resonance imaging. Mean diffusivity (MD) of the nbM and neuromelanin signal of the SN and LC were used as proxy measures of neurodegeneration.
ResultsnbM MD did not differ between PD patients and controls ({beta}=0.05, 95% CI [-0.27, 0.37], p=.771), a finding that was replicated using other MRI metrics. Higher nbM MD in PD patients was associated with worse executive function ({beta}=-0.22, 95% CI [-0.39, -0.05], pFDR=.027), controlling for degeneration in the SN and LC. An association with attention did not survive multiple comparisons correction ({beta}=-0.22, 95% CI [-0.41, -0.02], pFDR=.112), and there was no association with memory ({beta}=0.08, 95% CI [-0.15, 0.30], pFDR=.572). When considering both groups jointly, the relationship between increased nbM MD and worse executive function was stronger in PD than controls ({beta}nbM*Group=-0.30, 95% CI [-0.54, -0.06], pFDR=.036).
ConclusionOur findings suggest that in early-stage PD, nbM microstructural changes may account for unique variance in executive dysfunction in PD, independent of the effects of LC degeneration, and with a stronger association in PD than controls.
KEY MESSAGESO_ST_ABSWhat is already known on this topicC_ST_ABSAlthough cognitive deficits may stem, at least in part, from degeneration of cholinergic neurons in the nucleus basalis of Meynert (nbM), it is unknown whether this relationship is confounded by the parallel degeneration of the substantia nigra (SN) and the locus coeruleus (LC), and whether this relationship is unique to PD.
What this study addsThe novelty of our approach is that we considered the effects of the nbM, SN, and LC jointly rather than in isolation. We found that in early-stage PD, loss of nbM microstructural integrity was associated with executive dysfunction in PD, independent of the association of LC and executive dysfunction.
How this study might affect research, practice, or policyThese findings have important clinical implications because they suggest that the effects of degeneration in the cholinergic and noradrenergic system are at least partially independent and therefore could be targeted separately for remediating cognitive impairments.
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BibTeX
@misc{bailey2026nucleus,
title = {{Nucleus basalis of Meynert integrity is associated with cognitive dysfunction in Parkinson's disease independently of locus coeruleus degeneration}},
author = {A. Bailey and E. St-Onge and V. Madge and N. Shafiee and J.-F. Gagnon and A. Dagher and D. L. Collins and M. Sharp},
howpublished = {medRxiv},
year = {2026},
month = jul,
doi = {10.64898/2026.07.21.26358398},
url = {https://www.medrxiv.org/content/10.64898/2026.07.21.26358398v2},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Nucleus basalis of Meynert integrity is associated with cognitive dysfunction in Parkinson's disease independently of locus coeruleus degeneration
AU - A. Bailey
AU - E. St-Onge
AU - V. Madge
AU - N. Shafiee
AU - J.-F. Gagnon
AU - A. Dagher
AU - D. L. Collins
AU - M. Sharp
PY - 2026
DA - 2026/07/21
PB - medRxiv
DO - 10.64898/2026.07.21.26358398
UR - https://www.medrxiv.org/content/10.64898/2026.07.21.26358398v2
AB - BackgroundDegeneration in the cholinergic nucleus basalis of Meynert (nbM) is thought to contribute to early cognitive deficits in Parkinsons disease (PD). However, it is unknown whether this relationship is confounded by the parallel degeneration of the substantia nigra (SN) and the locus coeruleus (LC), and whether this relationship is unique to PD. MethodsWe conducted a cross-sectional analysis in 112 PD patients (disease duration <10 years) and 46 controls who underwent standard neuropsychological testing, diffusion-weighted and neuromelanin magnetic resonance imaging. Mean diffusivity (MD) of the nbM and neuromelanin signal of the SN and LC were used as proxy measures of neurodegeneration. ResultsnbM MD did not differ between PD patients and controls ({beta}=0.05, 95% CI [-0.27, 0.37], p=.771), a finding that was replicated using other MRI metrics. Higher nbM MD in PD patients was associated with worse executive function ({beta}=-0.22, 95% CI [-0.39, -0.05], pFDR=.027), controlling for degeneration in the SN and LC. An association with attention did not survive multiple comparisons correction ({beta}=-0.22, 95% CI [-0.41, -0.02], pFDR=.112), and there was no association with memory ({beta}=0.08, 95% CI [-0.15, 0.30], pFDR=.572). When considering both groups jointly, the relationship between increased nbM MD and worse executive function was stronger in PD than controls ({beta}nbM*Group=-0.30, 95% CI [-0.54, -0.06], pFDR=.036). ConclusionOur findings suggest that in early-stage PD, nbM microstructural changes may account for unique variance in executive dysfunction in PD, independent of the effects of LC degeneration, and with a stronger association in PD than controls. KEY MESSAGESO_ST_ABSWhat is already known on this topicC_ST_ABSAlthough cognitive deficits may stem, at least in part, from degeneration of cholinergic neurons in the nucleus basalis of Meynert (nbM), it is unknown whether this relationship is confounded by the parallel degeneration of the substantia nigra (SN) and the locus coeruleus (LC), and whether this relationship is unique to PD. What this study addsThe novelty of our approach is that we considered the effects of the nbM, SN, and LC jointly rather than in isolation. We found that in early-stage PD, loss of nbM microstructural integrity was associated with executive dysfunction in PD, independent of the association of LC and executive dysfunction. How this study might affect research, practice, or policyThese findings have important clinical implications because they suggest that the effects of degeneration in the cholinergic and noradrenergic system are at least partially independent and therefore could be targeted separately for remediating cognitive impairments.
ER -