The Topography of Brain Damage at Different Stages of Parkinson's Disease

Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
Human Brain Mapping (Impact Factor: 5.97). 11/2013; 34(11). DOI: 10.1002/hbm.22101
Source: PubMed


This study investigated gray matter (GM) and white matter (WM) damage in 89 patients at different clinical stages of Parkinson's disease (PD) (17 early, 46 mild, 14 moderate, and 12 severe) to differentiate the trajectories of tissue injury in this condition. PD patients had a very little GM atrophy even at the more advanced stages of the disease. Microstructural damage to the WM occurs with increasing PD severity and involves the brainstem, thalamocortical pathways, olfactory tracts, as well as the major interhemispheric, limbic, and extramotor association tracts. The most marked WM damage was found in moderate vs. mild cases. WM damage correlated with the degree of global cognitive deficits. WM abnormalities beyond the nigrostriatal system accumulate with increasing PD severity. WM damage is likely to contribute to the more severe motor and nonmotor dysfunctions occurring in patients at the later stages. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.

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    • "Using both VBM and TBSS analyses, these studies have consistently concluded that white matter and not gray matter changes underlie cognitive impairment in PD (Agosta et al. 2013a, b). This discrepancy may be due to the fact that VBM may not be highly sensitive for detecting subtle Brain Struct Funct cortical atrophy in early stages of PD (Agosta et al. 2013b; Jubault et al. 2011). In fact, cortical thickness analysis appeared more prone to detect cortical gray matter changes in PD than VBM when both analysis methods were compared (Pereira et al. 2012). "
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    ABSTRACT: The current study investigates both gray and white matter changes in non-demented Parkinson's disease (PD) patients with varying degrees of mild cognitive deficits and elucidates the relationships between the structural changes and clinical sequelae of PD. Twenty-six PD patients and 15 healthy controls (HCs) were enrolled in the study. Participants underwent T1-weighted and diffusion tensor imaging (DTI) scans. Their cognition was assessed using a neuropsychological battery. Compared with HCs, PD patients showed significant cortical thinning in sensorimotor (left pre- and postcentral gyri) and cognitive (left dorsolateral superior frontal gyrus [DLSFG]) regions. The DLSFG cortical thinning correlated with executive and global cognitive impairment in PD patients. PD patients showed white matter abnormalities as well, primarily in bilateral frontal and temporal regions, which also correlated with executive and global cognitive impairment. These results seem to suggest that both gray and white matter changes in the frontal regions may constitute an early pathological substrate of cognitive impairment of PD providing a sensitive biomarker for brain changes in PD.
    Full-text · Article · May 2014 · Brain Structure and Function
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    • "In the earliest disease stages and in cognitively intact patients, several studies have found either no global or regional gray matter volume loss [1] [11] [34] or they reported scant changes [35] [36]. In relation to memory tasks, VBM findings have been absent in untreated patients [10] [11] and restricted to the hippocampus when reported in cognitively intact PD patients [1]. "
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    ABSTRACT: Background: Free recall memory deficits are common in Parkinson's disease (PD), even at early stages before mild cognitive impairment or dementia. Their association with brain structural changes has not been established. Objective: We studied local gray matter volumes in relation to different memory tasks in early stage PD. Methods: Magnetic resonance images (MRI) and neuropsychological data were obtained from 28 non-demented, medicated PD patients, and 28 healthy controls. The gray matter segments of T1-weighted MRI images were analyzed using voxel-based morphometry in relation to visual and verbal memory tasks. Measures of immediate free recall, verbal learning, delayed recall and memory consolidation were obtained. A novel measure of incidental memory was included. Results: Patients and controls showed no significant group differences in local gray matter volumes. Voxel-based morphometry analyses revealed that worse performance on an incidental visual memory task was associated with smaller right parietal gray matter volume (Family-wise error corrected P = 0.002). This association was present in the PD group (corrected P = 0.005), but not in controls (corrected P > 0.99). No associations between gray matter volumes and the other memory tasks were found in either group. Conclusions: The results suggest that right parietal cortical gray matter volume is related to free recall memory deficits in early stage PD in conditions not involving an intention to memorize visual items. This preliminary finding needs to be established in further studies utilizing incidental memory tasks in PD.
    Full-text · Article · Nov 2013
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    ABSTRACT: Glucocerebrosidase gene mutations represent a genetic risk factor for the development of Parkinson's disease. This study investigated brain alterations in Parkinson's disease patients carrying heterozygous glucocerebrosidase gene mutations using structural and diffusion tensor magnetic resonance imaging. Among 360 Parkinson's disease patients screened for glucocerebrosidase gene mutations, 19 heterozygous mutation carriers (5.3%) were identified. Of these, 15 patients underwent a neuropsychological evaluation and a magnetic resonance imaging scan. Sixteen age- and sex-matched healthy controls and 14 idiopathic Parkinson's disease patients without glucocerebrosidase gene mutations were also studied. Tract-based spatial statistics was used to perform a white matter voxel-wise analysis of diffusion tensor magnetic resonance imaging metrics. Mean fractional anisotropy values were obtained from white matter tracts of interest. Voxel-based morphometry was used to assess gray-matter atrophy. Cognitive deficits were found in 9 mutation carrier patients (60%). Compared with controls, Parkinson's disease patients carrying glucocerebrosidase gene mutations showed decreased fractional anisotropy in the olfactory tracts, corpus callosum, and anterior limb of the internal capsule bilaterally, as well as in the right anterior external capsule, and left cingulum, parahippocampal tract, parietal portion of the superior longitudinal fasciculus, and occipital white matter. Mutation carrier patients also had decreased fractional anisotropy of the majority of white matter tracts compared with Parkinson's disease patients with no mutations. No white matter abnormalities were found in Parkinson's disease patients without glucocerebrosidase gene mutations. No gray matter difference was found between patients and controls. In Parkinson's disease patients, verbal fluency scores correlated with white matter abnormalities. Parkinson's disease patients carrying glucocerebrosidase gene mutations experience a distributed pattern of white matter abnormalities involving the interhemispheric, frontal corticocortical, and parahippocampal tracts. White matter pathology in these patients may have an impact on the clinical manifestations of the disease, including cognitive impairment. © 2013 Movement Disorder Society.
    No preview · Article · Jun 2013 · Movement Disorders
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