Objective: To assess the relationship between volumetric measures of cholinergic basal forebrain (CBF) degeneration and short-latency sensory afferent inhibition (SAI) in Parkinson’s disease (PD).

Background: Both CBF degeneration and altered SAI, which is believed to be mediated by cholinergic projections, have been independently associated with cognitive impairment in PD [1,2]. However, the relationship between both measures has not yet been tested in the context of PD.

Method: Fifty-seven PD patients, recruited prospectively from our movement disorders unit, underwent median nerve SAI and 3T structural MRI to determine the basal forebrain volume following published procedures [3,4]. In our primary analyses, we used the total anatomic CBF space as an overall measure of CBF degeneration, and in secondary analyses we considered functionally defined anterior-medial (aCBF) and posterior-lateral (pCBF) subdivisions separately. The Parkinson’s Disease Cognitive Rating Scale (PDCRS) [4] total score (PDCRS_T) and the fronto-subcortical (PDCRS_F-SC) and posterior cortical (PDCRS_P-C) subscores were used to assess the cognitive status of the participants. Partial correlations, controlling for age, sex, years of education, and total intracranial volume, were used for statistical analyses.

Results: The percentage of SAI showed significant positive correlations with the PDCRS_T score (Pearson’s r = 0.33, p = 0.016) and the PDCRS_P-C subscore (r = 0.54, p < 0.001), but not with PDCRS_F-SC (r = 0.24, p = 0.078). The total CBF volume showed significant positive correlations with all three PDRCS scores (all p < 0.05), which were most pronounced with the PDCRS_P-C score. Furthermore, we found a trend-level relationship between SAI and total CBF volume (r = 0.25, p = 0.073), which was driven by the pCBF (r = 0.32, p = 0.019; aCBF, r =0.14, p = 0.30).

Conclusion: Our results confirm that both CBF volume and the degree of cortical inhibition measured by SAI are associated with cognitive performance in PD, which reinforces the hypothesis of the role of cholinergic neurotransmission in the cognitive status of these patients. Furthermore, our results suggest that SAI represents a neurophysiological correlate of CBF degeneration in PD.

References: [1] Ray NJ et al. Brain 2018, 141: 165-75
[2] Martin-Rodriguez JF & Mir, P. Neuroscience Letters 2020, 719: 133679
[3] Tokimura H et al. Journal of Physiology 2000, 523: 503-13
[4] Fritz HJ et al. Human Brain Mapping 2019, 40: 868-78

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MDS Abstracts - https://www.mdsabstracts.org/abstract/relationship-between-cholinergic-basal-forebrain-volume-and-short-latency-sensory-afferent-inhibition-in-parkinsons-disease-with-varying-degrees-of-cognitive-performance/