Microstructural Patterns in Substantia Nigra Subregions Are Associated With Depression and Olfactory Impairments in Parkinson's Disease Publisher Pubmed



Mozafar M^{1, 2} ; Manshadi ZD³ ; Molaei Z⁴ ; Babaei H^{5, 6} ; Mansouri M^{7, 8} ; Shahbazi S^{9, 10} ; Shakeri S¹¹ ; Mirhosseini H¹² ; Gulisashvili D¹³ ; Mayeli M¹⁴
Source: Clinical Neurology and Neurosurgery Published:2025

Abstract

Objective: Parkinson's Disease (PD) manifests with both motor and non-motor symptoms, with non-motor symptoms often appearing first. The link between non-motor symptoms, particularly depression, and olfactory dysfunction, and substantia nigra (SN) subregions has been studied less. By utilizing Diffusion tensor imaging (DTI), we investigated the associations between microstructural patterns in the SN's subregions and motor and non-motor symptoms in patients with PD, including those without evident dopaminergic deficits, compared to healthy controls (HC). Methods: Complete baseline demographic data, motor assessments, full-scale non-motor tests, and DTI of SN subregions for 260 participants, including 156 with PD, 36 with scans without evidence of dopaminergic deficit (SWEDD), and 68 HC, were extracted from the PPMI database. Multiple linear regression models were used to evaluate the associations between symptom scores and DTI findings. Results: A significant difference in depression between the groups was found (p < 0.01), with patients with SWEDD having the highest rate of depression (approximately 36.1 %). Depressed SWEDD patients, compared to non-depressed ones, had higher FA values in the right rostral part of SN (p = 0.03, adjusted p = 0.15). Anxiety scores were significantly higher in both PD and SWEDD groups compared to HCs. PD patients exhibited a significantly higher prevalence of olfactory dysfunction compared to SWEDD and HCs (p < 0.001, adjusted p = 0.03), with 54.5 % of PD patients experiencing hyposmia and 34 % of them suffering from anosmia. PD patients with normosmia and hyposmia had higher FA in the right caudal SN than those with anosmia. Conclusion: Our findings suggest significant brain microstructural differences in SN associated with depression and olfactory dysfunction in patients with PD with or without evident dopaminergic deficits. This finding highlights the advantage of DTI in detecting microstructural changes in patients with SWEDD. © 2025 Elsevier B.V.