title: Linear and Curvilinear Trajectories of Cortical Loss with Advancing Age and Disease Duration in Parkinson's Disease.
abstract: Advancing age and disease duration both contribute to cortical thinning in Parkinson's disease (PD), but the pathological interactions between them are poorly described. This study aims to distinguish patterns of cortical decline determined by advancing age and disease duration in PD. A convenience cohort of 177 consecutive PD patients, identified at the Vanderbilt University Movement Disorders Clinic as part of a clinical evaluation for Deep Brain Stimulation (age: M= 62.0, SD 9.3), completed a standardized clinical assessment, along with structural brain Magnetic Resonance Imaging scan. Age and gender matched controls (n=53) were obtained from the Alzheimer Disease Neuroimaging Initiative and Progressive Parkinson's Marker Initiative (age: M= 63.4, SD 12.2). Estimated changes in cortical thickness were modeled with advancing age, disease duration, and their interaction. The best-fitting model, linear or curvilinear (2(nd), or 3(rd) order natural spline), was defined using the minimum Akaike Information Criterion, and illustrated on a 3-dimensional brain. Three curvilinear patterns of cortical thinning were identified: early decline, late decline, and early-stable-late. In contrast to healthy controls, the best-fit model for age related changes in PD is curvilinear (early decline), particularly in frontal and precuneus regions. With advancing disease duration, a curvilinear model depicts accelerating decline in the occipital cortex. A significant interaction between advancing age and disease duration is evident in frontal, motor, and posterior parietal areas. Study results support the hypothesis that advancing age and disease duration differentially affect regional cortical thickness and display regional dependent linear and curvilinear patterns of thinning.
authors.affiliation: 1Department of Neurology, Vanderbilt University, Nashville, TN 37235, USA.
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Claassen
authors.affiliation: 2McIntire School of Commerce, University of Virginia, Charlottesville, VA 22904, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Dobolyi
authors.affiliation: 1Department of Neurology, Vanderbilt University, Nashville, TN 37235, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Isaacs
authors.affiliation: 1Department of Neurology, Vanderbilt University, Nashville, TN 37235, USA.
authors.forename: Olivia C
authors.initials: OC
authors.lastname: Roman
authors.affiliation: 3Department of Medicine, University of Virginia, Charlottesville, VA 22904, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Herb
authors.affiliation: 1Department of Neurology, Vanderbilt University, Nashville, TN 37235, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Wylie
authors.affiliation: 4Department of Neurosurgery, Vanderbilt University, Nashville, TN 37235, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Neimat
authors.affiliation: 1Department of Neurology, Vanderbilt University, Nashville, TN 37235, USA; 5Department of Radiology, Vanderbilt University, Nashville, TN 37235, USA.
authors.forename: Manus J
authors.initials: MJ
authors.lastname: Donahue
authors.affiliation: 1Department of Neurology, Vanderbilt University, Nashville, TN 37235, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Hedera
authors.affiliation: 6Department of Psychology, Vanderbilt University, Nashville, TN 37235, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Zald
authors.affiliation: 5Department of Radiology, Vanderbilt University, Nashville, TN 37235, USA; 7Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA.
authors.forename: Bennett A
authors.initials: BA
authors.lastname: Landman
authors.affiliation: 1Department of Neurology, Vanderbilt University, Nashville, TN 37235, USA.
authors.forename: Aaron B
authors.initials: AB
authors.lastname: Bowman
authors.affiliation: 7Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA.
authors.forename: Benoit M
authors.initials: BM
authors.lastname: Dawant
authors.affiliation: 5Department of Radiology, Vanderbilt University, Nashville, TN 37235, USA.
authors.forename: Swati
authors.initials: S
authors.lastname: Rane
keywords: Aging; Cortex; Disease duration; MRI; Neurodegeneration; Parkinson’s disease