The pattern of gray matter atrophy in Parkinson’s disease differs in cortical and subcortical regions

Abstract

Background Cortical and subcortical gray matter (GM) atrophy may progress differently during the course of Parkinson's disease (PD). We delineated and compared the longitudinal pattern of these PD-related changes. Methods Structural MRIs and clinical measures were obtained from 76 PD with different disease durations and 70 Controls at baseline, 18- and 36-months. Both cortical and subcortical (putamen, caudate, and globus pallidus) GM volumes were obtained, compared, and associated with PD clinical measures at baseline. Their volumes and rates of change also were compared among Controls, PDs, and PD subgroups based on duration of illness [≤1 year (PDE), 1-5 years (PDM), and >5 years (PDL)]. Results Compared to Controls, PD subjects displayed smaller cortical GM and striatal (putamen, caudate, ps≤0.001), volumes at baseline. Cortical GM volumes were negatively associated with disease duration at baseline, whereas striatal volumes were not. PD subjects demonstrated accelerated volume loss in cortical GM (p=0.006), putamen (p=0.034), and caudate (p=0.008) compared to Controls. Subgroup analyses demonstrated that accelerated cortical atrophy reached statistical significance in PD subjects with duration of illness 1-5 years (PDM, ps<0.001) and the trend of accelerated atrophy seemed to persist until later stages, whereas striatal atrophy occurred in PD subjects with PDE (p=0.021 for putamen, p=0.005 for caudate) and PDM (p=0.002 for putamen, p=0.001 for caudate) that significantly slowed down in PDL (ps for PDL vs PDE or PDM: <0.01). Conclusions The pattern of GM loss in PD differs in cortical and subcortical regions, with striatal atrophy occurring earlier and extra-striatal cortical atrophy later.

Cortical gray and subcortical white matter associations in Parkinson's disease

“…Gray matter atrophy in PD has been reported by a number of groups (Hwang et al, 2013; Ibarretxe-Bilbao et al, 2012; Lewis et al, 2016; Pereira et al, 2014; Ramirez-Ruiz et al, 2007; Segura et al, 2014; Song et al, 2011; Tinaz et al, 2011; Zhang et al, 2014), and the current study confirmed these findings in a longitudinal cohort. On the other hand, past research has yielded inconsistent results regarding the extent and nature of white matter involvement in PD.…”

“…Cortical volume, however, may be a useful measure to detect overall structural changes during aging or disease processes, since it is the combined property of thickness and surface area. Indeed, loss of cortical volume has been documented both in healthy aging (Abe et al, 2008; Storsve et al, 2014) and Parkinson’s disease (PD) (Lewis et al, 2016), although the underlying mechanisms might be different. In healthy aging, dendrite losses and/or shrinkage of larger neurons (Terry et al, 1987) may drive the changes in cortical volume, since the number of cortical neurons is thought to remain relatively constant (Bartzokis et al, 2001; Freeman et al, 2008; Jernigan et al, 2001; Scheibel et al, 1975).…”

Pattern of Reduced Functional Connectivity and Structural Abnormalities in Parkinson’s Disease: An Exploratory Study

“…Previous longitudinal studies using different imaging analysis have suggested that striatal atrophy occurs earlier in the disease process, while cortical GM loss is restricted to later stages, reduced overall gyrification, and bilaterally in the inferior parietal, postcentral, precentral, superior frontal, and supramarginal areas was present in patients with disease for less than 1 year, and the rate loss was accelerated as disease progressed (37). Although our subjects presented some homogeneity in their mean clinical scale scores per group (with lower scores in the mild group, intermediate in the moderate group, and higher scores in the severe group in the motor and non-motor scales), we classified them solely based on their HY score.…”

Distinct progression pattern of susceptibility MRI in the substantia nigra of Parkinson's patients

“…Demographic and clinical characteristics, the Movement Disorder Society Unified PD Rating Scale parts I, II, and III (MDS‐UPDRS‐I, ‐II, ‐III); levodopa‐equivalent daily dosage (LEDD); the Montreal Cognitive Assessment (MoCA); the Hamilton Depression Rating Scale (HDRS); and the PD Questionnaire (PDQ‐39) were obtained from all participants every 6 months, while patients were on optimized antiparkinsonian medications (ON state). PD subgroups (early‐stage PD [PDE], < 1 year; middle‐stage PD [PDM], < 5 years; and later‐stage PD [PDL], > 5 years) were created based on time after first documented Parkinson's disease diagnosis, as done previously . Detailed demographic data (for PD subgroups at the baseline and follow‐up visits) are provided in Supplementary Table 1.…”

“…PD subgroups (early-stage PD [PDE], < 1 year; middlestage PD [PDM], < 5 years; and later-stage PD [PDL], > 5 years) were created based on time after first documented Parkinson's disease diagnosis, as done previously. 29 Detailed demographic data (for PD subgroups at the baseline and follow-up visits) are provided in Supplementary Table 1. All participants gave written informed consent that was in accordance with the Declaration of Helsinki and approved by the Penn State Hershey Institutional Review Board.…”