Cortical atrophy patterns associated to cognitive impairment in Parkinson’s disease
[eng] BACKGROUND AND OBJECTIVES. Parkinson’s disease is a heterogenous neurodegenerative disorder. To characterize homogeneous groups of PD patients, PD phenotypes have been described based on clinical data including motor and non-motor manifestations. This thesis is presented as a compendium of thr...
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| Formato: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2019 |
| País: | España |
| Recursos: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/145705 |
| Acesso em linha: | https://hdl.handle.net/2445/145705 http://hdl.handle.net/10803/668039 |
| Access Level: | acceso abierto |
| Palavra-chave: | Malaltia de Parkinson Ressonància magnètica Anàlisi de conglomerats Parkinson's disease Magnetic resonance Cluster analysis |
| Resumo: | [eng] BACKGROUND AND OBJECTIVES. Parkinson’s disease is a heterogenous neurodegenerative disorder. To characterize homogeneous groups of PD patients, PD phenotypes have been described based on clinical data including motor and non-motor manifestations. This thesis is presented as a compendium of three research studies. The aim was to identify different PD subtypes based on objective MRI measures of cortical thickness. We hypothesized that different patterns of regional brain atrophy would be associated to distinct clinical and cognitive features. METHODS. We have used T1-weighted MRI images acquired with 3T Siemens scanners in two sample of PD patients at different times of the disease evolution: a sample of medicated PD patients (n = 88; disease duration: 8 ± 5.7 years) and a second sample from the Parkinson Progression Marker Initiative (PPMI, https://www.ppmi-info.org/) that enrolled 119 PD newly diagnosed drug naïve patients (n = 77; disease duration: 0.9 ± 1.0 years) with available MRI and neuropsychological assessments. Additionally, the medicated sample was followed-up after four years (n = 45). Both PD samples were compared with two similar groups of healthy elders. Cortical thickness estimation was performed with the FreeSurfer suite v5.1 (https://surfer.nmr.mgh.harvard.edu/). An agglomerative hierarchical cluster analysis technique was used to classify patients from a hypothesis-free data driven approach using Matlab (release 2014b, The MathWorks, Inc., Natick, Massachusetts). For the longitudinal assessment, we computed the symmetrized percent of change of the cortical thickness estimation of both times. RESULTS. In Study 1, we firstly classified patients of the medicated sample according to the vertex-wise cortical thickness data. Three patterns of regional thinning were obtained when comparing them with a sample of healthy controls with similar age and education: (1) a pattern mainly involving temporal and parietal atrophy; (2) a second pattern with frontal and occipital and younger age at disease onset; (3) a third pattern with no manifest atrophy in comparison with controls and reduced processing speed. In Study 2, we classified the PD de novo patients according to their cortical thickness information from the 360 parcellations of the Human Connectome Project Multi-Modal Parcellation version 1.0. Two PD patterns were identified: (1) one pattern with anterior predominance including orbitofrontal, anterior cingulate and temporal atrophy with no cognitive deficits and (2) a posterior-based pattern with lateral occipital and parietal atrophy with associated verbal memory learning and delayed recall deficits as well as visuospatial and processing speed impairment. In Study 3, we assessed the progression of the cortical patterns identified in Study 1 over four years. Pattern 1 patients with initial temporal and parietal widespread atrophy had worse compromise in the activities of daily living. Regarding the other two patterns and the controls group, all groups displayed temporo-parietal progressive decline and reduced processing speed. However, pattern 2 patients with initial prefrontal involvement and younger disease onset had better evolution and focal cortical thinning changes. Pattern 3 patients and controls, that at baseline were the less atrophic groups, displayed extensive symmetrized percent of change in temporal and parietal regions. Despite the similar progression of pattern 3 with controls, pattern 3 patients had more atrophy in the prefrontal cortex over time than controls and more decline in semantic fluency, processing speed and visuospatial function. CONCLUSIONS. PD patients showed different patterns of cortical thinning even at the time of diagnosis, regardless the presence of mild cognitive impairment and medication doses. Our patterned groups of patients based on hypothesis free data-driven methodologies stress the importance to review neuropsychological tools for the diagnosis of PD-MCI. Cortical thickness measures of percent of change revealed sensitive to aging and specific cortical degeneration in PD. Different regional atrophy patterns progress differently over time. It has been observed that initial posterior-based atrophy had worse compromise in the activities of daily living and patients were more likely to progress to dementia, whereas initial prefrontal involvement is linked to a better clinical evolution. Overall, data-driven analyses were able to classify PD patients based on their cortical degeneration depicting distinct clinical manifestations and different progressions. Thus, PD prognosis can be characterized by structural MRI data. |
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