Altered resting state brain metabolic connectivity in dementia with Lewy bodies

Abstract

Although dementia with Lewy bodies (DLB) have Parkinsonism in common with Parkinson's disease (PD) or PD dementia (PDD), they have different neuropathologies that underlie Parkinsonism. Altered brain functional connectivity that may correspond to neuropathology has been reported in PD while never been studied in DLB. To identify the characteristic brain connectivity of Parkinsonism in DLB, we compared the resting state metabolic connectivity in striato-thalamo-cortical (STC) circuit, nigrostriatal pathway, and cerebello-thalamo-cortical motor (CTC) circuit in 27 patients with drug-naïve DLB and 27 age- and sex-matched normal controls using 18F-fluoro-2-deoxyglucose PET. We derived 118 regions of interest using the Automated Anatomical Labeling templates and the Wake Forest University Pick-Atlas. We applied the sparse inverse covariance estimation method to construct the metabolic connectivity matrix. Patients with DLB, with or without Parkinsonism, showed lower inter-regional connectivity between the areas included in the STC circuit (motor cortex–striatum, midbrain–striatum, striatum–globus pallidus, and globus pallidus–thalamus) than the controls. DLB patients with Parkinsonism showed less reduced inter-regional connectivity between the midbrain and the striatum than those without Parkinsonism, and higher inter-regional connectivity between the areas included in the CTC circuit (motor cortex–pons, pons–cerebellum, and cerebellum–thalamus) than those without Parkinsonism and the controls. The resting state metabolic connectivity in the STC circuit may be reduced in DLB. In DLB with Parkinsonism, the CTC circuit and the nigrostriatal pathway may be activated to mitigate Parkinsonism. This difference in the brain connectivity may be a candidate biomarker for differentiating DLB from PD or PDD.