Objective: Investigate differences in white matter integrity of the nucleus basalis of Meynert (NBM) tracts in Parkinson’s disease (PD) patients who develop mild cognitive impairment (MCI) versus those that maintain healthy cognition.

Background: Among the most disabling non-motor PD symptoms, cognitive decline is evident in approximately one third of recently diagnosed patients. Treatments for cognitive impairment remain scarce and ineffective. Thus, greater understanding of the neurobiology underlying cognitive decline in PD is needed to aid the development of effective interventions. At the epicenter of the cortical cholinergic network, the NBM degenerates early in PD and is crucial for cognitive domains most vulnerable to PD. The two main white matter pathways stemming from the NBM include a lateral trajectory through the external capsule, and a medial pathway through the cingulum. However, research is needed to determine which pathway, if any, are associated with PD-related cognitive decline.

Method: Thirty-seven PD patients (Aged 38-77; Females=15) with no MCI at baseline from the Parkinson’s Progression Markers Initiative (PPMI) dataset were included in this study. Probable MCI was determined by a score <26 on the Montreal Cognitive Assessment. Participants were characterized as those that either developed MCI at 1 year follow up (MCI-Converters; n=16) or did not (non-Converters; n=21). Probabilistic tractography of the medial and lateral tracts originating from the NBM was performed and the mean diffusivity (MD) of these tracts compared between groups using univariate ANCOVA, controlling for age and sex. Control comparisons of MD in the external capsule and cingulum regions were also performed.

Results: MCI-Converters had significantly greater MD of the lateral NBM tract at baseline than non-Converters (F=11.0, p=.015). There were no significant differences between groups in the medial tract or in either of the control regions.

Conclusion: Reduced integrity of the lateral NBM tract specifically is evident in PD patients who develop MCI up to one year prior to the development of MCI. Thus, deterioration of the lateral NBM tract in PD may be an early marker of those at risk of cognitive decline.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/no-laughing-white-matter-reduced-integrity-of-the-lateral-nucleus-basalis-of-meynert-pathway-in-parkinsons-disease-related-cognitive-impairment/