Neuromelanin related ultra-high field signal intensity of the locus coeruleus differs between Parkinson's disease and controls.

INTRODUCTION: Neuromelanin related signal changes in catecholaminergic nuclei are considered as a promising MRI biomarker in Parkinson's disease (PD). Until now, most studies have investigated the substantia nigra (SN), while signal changes might be more prominent in the locus coeruleus (LC). Ultra-high field MRI improves the visualisation of these small brainstem regions and might support the development of imaging biomarkers in PD. OBJECTIVES: To compare signal intensity of the SN and LC on Magnetization Transfer MRI between PD patients and healthy controls (HC) and to explore its association with cognitive performance in PD. METHODS: This study was conducted using data from the TRACK-PD study, a longitudinal 7T MRI study. A total of 78 early-stage PD patients and 36 HC were included. A mask for the SN and LC was automatically segmented and manually corrected. Neuromelanin related signal intensity of the SN and LC was compared between PD and HC. RESULTS: PD participants showed a lower contrast-to-noise ratio (CNR) in the right SN (p = 0.029) and left LC (p = 0.027). After adding age as a confounder, the CNR of the right SN did not significantly differ anymore between PD and HC (p = 0.055). Additionally, a significant positive correlation was found between the SN CNR and memory function. DISCUSSION: This study confirms that neuromelanin related signal intensity of the LC differs between early-stage PD patients and HC. No significant difference was found in the SN. This supports the theory of bottom-up disease progression in PD. Furthermore, loss of SN integrity might influence working memory or learning capabilities in PD patients.

Brain network characteristics and cognitive performance in motor subtypes of Parkinson's disease: A resting state fMRI study.

INTRODUCTION: Parkinson's disease (PD) is a heterogeneous disorder with great variability in motor and non-motor manifestations. It is hypothesized that different motor subtypes are characterized by different neuropsychiatric and cognitive symptoms, but the underlying correlates in cerebral connectivity remain unknown. Our aim is to compare brain network connectivity between the postural instability and gait disorder (PIGD) and tremor-dominant (TD) subtypes, using both a within- and between-network analysis. METHODS: This cross-sectional resting-state fMRI study includes 81 PD patients, 54 belonging to the PIGD and 27 to the TD subgroup. Group-level spatial maps were created using independent component analysis. Differences in functional connectivity were investigated using dual regression analysis and inter-network connectivity analysis. An additional voxel-based morphometry analysis was performed to examine if results were influenced by grey matter atrophy. RESULTS: The PIGD subgroup scored worse than the TD subgroup on all cognitive domains. Resting-state fMRI network analyses suggested that the connection between the visual and sensorimotor network is a potential differentiator between PIGD and TD subgroups. However, after correcting for dopaminergic medication use these results were not significant anymore. There was no between-group difference in grey matter volume. CONCLUSION: Despite clear motor and cognitive differences between the PIGD and TD subtypes, no significant differences were found in network connectivity. Methodological challenges, substantial symptom heterogeneity and many involved variables make analyses and hypothesis building around PD subtypes highly complex. More sensitive visualisation methods combined with machine learning approaches may be required in the search for characteristic underpinnings of PD subtypes.

Comparison of Olfactory Tract Diffusion Measures Between Early Stage Parkinson's Disease Patients and Healthy Controls Using Ultra-High Field MRI.

BACKGROUND: MRI is a valuable method to assist in the diagnostic work-up of Parkinson's disease (PD). The olfactory tract (OT) has been proposed as a potential MRI biomarker for distinguishing PD patients from healthy controls. OBJECTIVE: This study aims to further investigate whether diffusion measures of the OT differ between early stage PD patients and healthy controls. METHODS: Twenty hyposmic/anosmic PD patients, 65 normosmic PD patients, and 36 normosmic healthy controls were evaluated and a 7T diffusion weighted image scan was acquired. Manual seed regions of interest were drawn in the OT region. Tractography of the OT was performed using a deterministic streamlines algorithm. Diffusion measures (fractional anisotropy and mean- radial- and axial diffusivity) of the generated streamlines were compared between groups. RESULTS: Diffusion measures did not differ between PD patients compared to healthy controls and between hyposmic/anosmic PD patients, normosmic PD patients, and normosmic healthy controls. A positive correlation was found between age and mean- and axial diffusivity within the hyposmic/anosmic PD subgroup, but not in the normosmic groups. A positive correlation was found between MDS-UPDRSIII scores and fractional anisotropy. CONCLUSION: This study showed that fiber tracking of the OT was feasible in both early stage PD and healthy controls using 7T diffusion weighted imaging data. However, 7T MRI diffusion measures of the OT are not useful as an early clinical biomarker for PD. Future work is needed to clarify the role of other OT measurements as a biomarker for PD and its different subgroups.

Grey matter abnormalities are associated only with severe cognitive decline in early stages of Parkinson's disease.

Cognitive impairment is common in Parkinson's disease (PD), yet with large heterogeneity in the range and course of deficits. In a cross-sectional study, 124 PD patients underwent extensive clinical and neuropsychological assessment as well as a 3T MRI scan of the brain. Our aim was to identify differences in grey matter volume and thickness, as well as cortical folding, across different cognitive profiles as defined through a data-driven exploratory cluster analysis of neuropsychological data. The identified cognitive groups ranged from cognitively intact patients to patients with severe deficits in all cognitive domains, whilst showing comparable levels of motor disability and disease duration. Each group was compared to the cognitively intact PD group using voxel- and vertex-based morphometry. Results revealed widespread age-related grey matter abnormalities associated with progressive worsening of cognitive functions in mild PD. When adjusted for age, significant differences were only seen between cognitively intact and severely affected PD patients and these were restricted to the right posterior cingulate and the right precuneus. Reduced cortical thickness was seen in the right inferior temporal gyrus and reduced folding in the right temporal region. As these differences were not associated with age, we assume that they are associated with underlying pathology of the cognitive decline. Given the limited involvement of grey matter differences, and the absence of differences in vascular changes across the groups, we hypothesize a more important role for white matter tract changes in cognitive decline in PD.

Resting-state fMRI in Parkinson's disease patients with cognitive impairment: A meta-analysis.

BACKGROUND: Cognitive impairment is a common non-motor symptom in Parkinson's disease. So far, the underlying pathophysiology remains unclear. Several alterations in functional network connectivity have been described in Parkinson's disease patients with cognitive impairment which are probably the result of the heterogenous pathophysiology underlying this cognitive decline, including dopaminergic and cholinergic deficits. Accordingly, the reported resting-state connectivity patterns vary greatly among studies. OBJECTIVE: To evaluate the localization and magnitude of functional connectivity patterns in resting-state brain networks in Parkinson's disease patients with cognitive impairment by pooling data from available studies. METHODS: We searched PubMed, the Cochrane Library, MEDLINE, Embase and PsycINFO to identify functional MRI studies in Parkinson's disease patients with cognitive impairment. A voxel-based meta-analysis combined with quality statistics was performed, using the anisotropic effect-size version of the signed differential mapping method. RESULTS: Seventeen studies with cognitively impaired Parkinson's disease patients were included consisting of 222 Parkinson's disease patients with mild cognitive impairment, 68 patients with Parkinson's disease dementia, 289 cognitively unimpaired Parkinson's disease patients and 353 healthy controls. Parkinson's disease patients with cognitive impairment predominantly showed a reduced connectivity in specific brain regions that are part of the default mode network. CONCLUSION: Cognitive impairment in Parkinson's disease is associated with reduced connectivity in networks relevant to cognition, most prominently the default mode network. Specific alterations in functional connectivity may contribute to cognitive decline in Parkinson patients and may be a promising future biomarker.