RESUMO
Peripheral artery disease (PAD) carries a high burden of morbidity when identified in patients with coronary artery disease (CAD). However, identification of patients with concomitant CAD and PAD remains challenging. Using linked administrative databases of 207,026 individuals with CAD between 2002 and 2019 (median follow-up, 4.7 years), a model for PAD was applied to identify baseline PAD and the development of PAD during follow-up. Both baseline PAD and future PAD models demonstrated poor calibration and discrimination (c-statistic 0.618 and 0.583). In the absence of additional variables, the present models are unable to identify patients with concomitant CAD and PAD.
La maladie artérielle périphérique (MAP) impose un lourd fardeau de morbidité lorsqu'elle est diagnostiquée chez les patients atteints de coronaropathie. Toutefois, il reste difficile de repérer les patients atteints à la fois de coronaropathie et de MAP. À partir de bases de données administratives liées comptant 207 026 personnes atteintes de coronaropathie entre 2002 et 2019 (suivi médian de 4,7 ans), un modèle pour la MAP a été appliqué afin de repérer une MAP initiale et l'apparition d'une MAP au cours du suivi. Les modèles de MAP initiale et de MAP future ont tous deux été associés à un calibrage et à une capacité de distinction insatisfaisants (statistique C de 0,618 et 0,583). En l'absence d'autres variables, les modèles actuels sont incapables de repérer les patients atteints de coronaropathie et de MAP concomitantes.
RESUMO
Parkinson's disease (PD) is a movement disorder characterized by the early loss of nigrostriatal dopaminergic pathways producing significant network changes impacting motor coordination. Recently three motor stages of PD have been proposed (a silent period when nigrostriatal loss begins, a prodromal motor period with subtle focal manifestations, and clinical PD) with evidence that motor cortex abnormalities occur to produce clinical PD[8]. We directly assess structural changes in the primary motor cortex and corticospinal tract using parallel analyses of longitudinal clinical and cross-sectional pathological cohorts thought to represent different stages of PD. 18F-FP-CIT positron emission tomography and subtle motor features identified patients with idiopathic rapid-eye-movement sleep behaviour disorder (n = 8) that developed prodromal motor signs of PD. Longitudinal diffusion tensor imaging before and after the development of prodromal motor PD showed higher fractional anisotropy in motor cortex and corticospinal tract compared to controls, indicating adaptive structural changes in motor networks in concert with nigrostriatal dopamine loss. Histological analyses of the white matter underlying the motor cortex showed progressive disorientation of axons with segmental replacement of neurofilaments with α-synuclein, enlargement of myelinating oligodendrocytes and increased density of their precursors. There was no loss of neurons in the motor cortex in early or late pathologically confirmed motor PD compared to controls, although there were early cortical increases in neuronal neurofilament light chain and myelin proteins in association with α-synuclein accumulation. Our results collectively provide evidence of a direct impact of PD on primary motor cortex and its output pathways that begins in the prodromal motor stage of PD with structural changes confirmed in early PD. These adaptive structural changes become considerable as the disease advances potentially contributing to motor PD.
