ArticleJournal of neurology2024
LRRK2 mutation contributes to decreased free water in the nucleus basalis of Meynert in manifest and premanifest Parkinson's disease.
Article in Journal of neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Increased free water in the nucleus basalis of Meynert is associated with worse olfaction in idiopathic Parkinson's disease.Frontiers in aging neuroscience · 2025Article
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8 authors.
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Abstract
backgroundFree-water imaging can predict and monitor dopamine system degeneration in patients with Parkinson's disease (PD). However, brain cholinergic function has not been investigated to date in LRRK2 mutation carriers with or without PD using free-water imaging.
objectivesTo investigate the effect of LRRK2 mutations on the cholinergic system in manifest and premanifest stages of PD using free-water imaging.
methodsWe recruited participants from the Parkinson's Progression Markers Initiative (PPMI) data set. We evaluated the effect of LRRK2 mutations on the cholinergic nuclei (i.e., cholinergic nuclei 1, 2, and 3 (Ch123), Ch4, and pedunculopontine nucleus) in manifest and premanifest stages of PD using free-water imaging. We compared free-water values between groups using ANCOVA with adjustment for age. Then, the discriminative power of the free-water content was evaluated by receiver operating characteristic curve (ROC) analysis.
resultsWe included 27 patients with LRRK2 PD, 33 LRRK2 mutation carriers without PD, 281 patients with idiopathic PD, and 98 healthy controls. We noted significant between-group differences in free-water content in Ch4 (p = 0.003). LRRK2 mutation carriers without PD had decreased free-water content in the Ch4 compared with healthy controls (p = 0.036) and idiopathic patients with PD (p = 0.001); LRRK2 patients with PD showed decreased tendency of free-water content in the Ch4 compared with idiopathic patients with PD (p = 0.074). Furthermore, ROC analysis showed that free-water content in the Ch4 identified asymptomatic LRRK2 mutation carriers with a high specificity (84.7%).
conclusionsLRRK2 mutation is associated with decreased free-water content in the Ch4 (also referred to as nucleus basalis of Meynert, nbM), which might suggest early and sustained attempts to compensate for LRRK2-related dysfunction.
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