Purpose of review: Neuroimaging in Parkinson's disease is an evolving field, providing in-vivo insights into the structural and biochemical changes of the condition, although its diagnosis remains clinical. Here, we aim to summarize the most relevant recent advances in neuroimaging in Parkinson's disease to assess the underlying disease process, identify a biomarker of disease progression and guide or monitor therapeutic interventions. Recent findings: The clinical applications of imaging technology increasingly allow to quantify pigments (iron, neuromelanin) on MRI, proteins (tau), cell markers (phosphodiesterases, microglia) and neurotransmitter receptors (dopamine, serotonin, noradrenalin, cholin) via PET protocols, activity maps by resting-state and task-dependent functional MRI, as well as microstructural changes (free water) through diffusion-based assessments. Their application provides increasing insight on the temporal and spatial dynamics of dopaminergic and other neurotransmitter systems as well as anatomical structures and circuits in Parkinson's disease. An expanding list of PET tracers increases the yield of functional studies. Summary: This review summarizes the most recent, relevant advances in neuroimaging technology in Parkinson's disease. In particular, the combination of different imaging techniques seems promising to maximize the scope of future work, which should, among others, aim at identifying the best imaging marker of disease progression.

Deep brain stimulation (DBS) is an established treatment for Parkinson disease (PD). In patients carrying GBA1 variants (GBA-PD), concerns persist that DBS may accelerate cognitive decline. This study investigated the potential additive effects of GBA1 genotype and DBS on long-term motor and nonmotor outcomes. This multicenter retrospective, controlled, Italian study included 3 groups: DBS-treated PD patients either carrying or noncarrying GBA1 variants (DBS-nonGBA-PD and DBS-GBA-PD) and GBA-PD patients who fulfilled DBS criteria but eventually were not operated. As secondary aims, we assessed the clinical outcomes of DBS-GBA-PD stratified by GBA1 variant classes and by different DBS targets. Cognitive, motor, and other nonmotor features were collected at baseline and after 1, 3 and, when available, 5 years. Between-group comparisons used χ² and Kruskal-Wallis tests with Bonferroni correction. Longitudinal changes were analyzed with linear mixed-effects models. Subgroup analyses were performed by GBA1 variant class and DBS target. A total of 615 participants were included: 430 DBS-nonGBA-PD (age 57.4 ± 7.7 years, 32% female), 109 DBS-GBA-PD (age 53.5 ± 8.4 years, 38% female), and 76 nonDBS-GBA-PD (age 57.7 ± 8.1 years, 37% female). At baseline, groups were largely matched for clinical features. Longitudinally, both DBS groups showed marked motor improvement (dyskinesias, on-off phenomenon, and wearing-off, all p vs T0 < 0.001), a benefit which was absent in nonDBS-GBA-PD. At 5 years, dementia occurred more frequently in DBS-GBA-PD and nonDBS-GBA-PD compared with DBS-nonGBA-PD (25.5% vs 36.8% vs 10.8%, p < 0.001). Hallucinations and urinary problems increased in both GBA-PD groups than nonGBA-PD (p-between <0.001 and 0.02, respectively), regardless of DBS. No relevant differences emerged on stratification for variant classes or DBS targets, up to 3 years postsurgery. Despite its retrospective design, this study supports DBS as a valid therapeutic option for GBA-PD, providing prolonged benefits on motor symptoms and quality of life. The accelerated cognitive decline observed in GBA-PD, compared with non-mutated participants, was similarly present in both operated and non-operated groups, suggesting it is driven by the genotype rather than DBS itself. This study provides Class III evidence that DBS does not worsen cognitive function in patients with GBA1-associated PD.