Objective: To examine the association between the integrity of the cholinergic basal forebrain (cBF) and cognition in Parkinson’s disease (PD).

Background: Most PD patients experience cognitive impairment, albeit at variable rates and with variable expression. About 50% progress to Parkinson’s disease dementia (PDD) by 10 years post-diagnosis [2]. Understanding the underlying neural changes is needed to improve prediction for those at greatest risk. cBF integrity may be a key factor.

Method: We acquired structural and diffusion-weighted magnetic resonance imaging for 108 participants with PD and 41 controls (Con). Using Level II assessment, PD were identified as showing normal cognition (PD-N, n = 60) through PD-MCI (n = 37) and PDD (n = 12). Metrics of volume, mean diffusivity (MD) and free water (FW) fraction were extracted from regions of the cBF as defined by Kilimann et al. (2014) [1].

Results: Accounting for age and sex, Bayesian mixed-effects models indicated reduced volume, reduced MD, and increased FW in the posterior subregion of Ch4 (Ch4p) were associated with lower global cognition scores in PD, but not in controls. For Ch4p, increased FW and reduced volume were especially evident in PDD (Cohen’s d (FW, PD-N–PDD) = 0.90; Cohen’s d (volume, Con–PDD) = 0.47), whereas decreased MD was detected in both PD-MCI and PDD relative to PD-N (respectively, Cohen’s d = 0.45, and Cohen’s d = 0.85). Lower volume was also associated with diminished global cognitive scores in the Ch1-2 and anterior lateral Ch4 (Ch4al) regions in PD, but not in controls. Reduced MD in Ch1-2 correlated with global cognitive scores for both PD and control participants.

Conclusion: These findings extend the association of diminished cBF structural integrity in PD-related cognitive impairment. However, this degradation is not uniform across the cBF. Longitudinal study is required to establish the potential of these effects as a predictor of future dementia in PD.

References: [1] Kilimann, I., Grothe, M., Heinsen, H., Alho, E. J., Grinberg, L., Amaro, E., Jr, Dos Santos, G. A., da Silva, R. E., Mitchell, A. J., Frisoni, G. B., Bokde, A. L., Fellgiebel, A., Filippi, M., Hampel, H., Klöppel, S., & Teipel, S. J. (2014). Subregional basal forebrain atrophy in Alzheimer’s disease: a multicenter study. Journal of Alzheimer’s disease : JAD, 40(3), 687–700. https://doi.org/10.3233/JAD-132345

[2] Aarsland, D., Batzu, L., Halliday, G.M. et al. Parkinson disease-associated cognitive impairment. Nat Rev Dis Primers 7, 47 (2021). https://doi.org/10.1038/s41572-021-00280-3

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cholinergic-basal-forebrain-integrity-and-cognition-in-parkinsons-disease/