Objective: We aimed to identify structural and functional brain MRI features of most aggressive phenotypes comparing three clusters of patients with idiopathic and genetic Lewy body (LB) diseases classified according to severity of non-motor manifestations.

Background: The pattern of brain damage in aggressive LB diseases may help to improve our understanding of the spectrum of idiopathic Parkinson’s disease (iPD).

Method: Three subtypes based on hierarchical clustering analysis of non-motor manifestations (cognition, autonomic, olfactory, ophthalmological and clinical features) were previously identified. Cluster 1 “Normal-to-mild” was characterized by having normal-to-mild cognitive disabilities and mild-to-moderate motor disability with few axial symptoms (n= 3 E46K-SNCA, 2 LRRK2 and 2 PARK2 mutation carriers and 14 iPD); Cluster 2 “Mild-to-moderate” characterized by having mild-to-moderate cognitive and motor disabilities with few axial symptoms (n= 1 E46K-SNCA, 1 PARK2 and 15 iPD); and Cluster 3 “Severe” characterized by having severe pattern-specific cognitive disabilities and severe motor PD manifestations with marked axial symptoms (n= 3 E46K-SNCA, 1 LRRK2, 1 PARK2, 19 iPD, 8 dementia with LB (DLB) [table1]. Seventy participants underwent T1-weighted, diffusion-weighted, and resting-state functional MRI. Voxel-based morphometry, tract-based spatial statistics and resting-state functional connectivity (FC) analyses were performed. The selected networks were based on FC atlas from CONN toolbox: Default Mode Network, Sensorimotor, Visual, Salience, Dorsal Attention, Central Executive, Language and Cerebellar.

Results: “Severe” cluster showed grey matter (GM) atrophy in temporal and parietal areas, white matter alterations in corpus callosum and anterior thalamic radiation, and FC reductions between language network and dorsal attention and salience networks. “Mild-to-moderate” cluster revealed GM atrophy in fronto-temporal areas, and FC reduction between salience and language networks [Figure1]. No significant alterations were found in “Normal-to-mild” cluster.

Conclusion: Our study supports the value of incorporating genetic PD variants in data-driven iPD classification, facilitating, when tested longitudinally, early identification of aggressive LB diseases developing dementia or other severe non-motor PD features.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/structural-and-functional-mri-brain-alterations-of-lewy-body-diseases/