Nucleus basalis of Meynert integrity is associated with cognitive dysfunction in Parkinson’s disease independently of locus coeruleus degeneration
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Background
Degeneration in the cholinergic nucleus basalis of Meynert (nbM) is thought to contribute to early cognitive deficits in Parkinson’s 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.
Methods
We 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.
Results
nbM MD did not differ between PD patients and controls (β=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 (β=-0.22, 95% CI [−0.39, −0.05], p FDR =.027), controlling for degeneration in the SN and LC. An association with attention did not survive multiple comparisons correction (β=-0.22, 95% CI [−0.41, −0.02], p FDR =.112), and there was no association with memory (β=0.08, 95% CI [−0.15, 0.30], p FDR =.572). When considering both groups jointly, the relationship between increased nbM MD and worse executive function was stronger in PD than controls (β nbM * Group =-0.30, 95% CI [−0.54, −0.06], p FDR =.036).
Conclusion
Our 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 MESSAGES
What is already known on this topic
Although 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 adds
The 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 policy
These 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.
