Additional file 1: Table S1. of Combining adverse pregnancy and perinatal outcomes for women exposed to antiepileptic drugs during pregnancy, using a latent trait model

Operational Definition 625 for Component Outcomes. Table S2. Demographic Characteristics and Missing Data of Study Participants. Table S3. Observed Frequency (OBFREQ), Expected Frequency (EXFREQ), Observed Percents (OB%), Expected Percents (EX%), Estimates of Posterior Mean of the Latent Variable S ̂ 632 and the APO by Combinations of Four Observed Outcomes. (DOCX 23 kb

Gray and White Matter Contributions to Cognitive Frontostriatal Deficits in Non-Demented Parkinson's Disease

<div><p>Objective</p><p>This prospective investigation examined: 1) processing speed and working memory relative to other cognitive domains in non-demented medically managed idiopathic Parkinson’s disease, and 2) the predictive role of cortical/subcortical gray thickness/volume and white matter fractional anisotropy on processing speed and working memory.</p><p>Methods</p><p>Participants completed a neuropsychological protocol, Unified Parkinson’s Disease Rating Scale, brain MRI, and fasting blood draw to rule out vascular contributors. Within group <i>a priori</i> anatomical contributors included bilateral frontal thickness, caudate nuclei volume, and prefrontal white matter fractional anisotropy.</p><p>Results</p><p>Idiopathic Parkinson’s disease (n = 40; Hoehn & Yahr stages 1–3) and non-Parkinson’s disease ‘control’ peers (n = 40) matched on demographics, general cognition, comorbidity, and imaging/blood vascular metrics. Cognitively, individuals with Parkinson’s disease were significantly more impaired than controls on tests of processing speed, secondary deficits on working memory, with subtle impairments in memory, abstract reasoning, and visuoperceptual/spatial abilities. Anatomically, Parkinson’s disease individuals were not statistically different in cortical gray thickness or subcortical gray volumes with the exception of the putamen. Tract Based Spatial Statistics showed reduced prefrontal fractional anisotropy for Parkinson’s disease relative to controls. Within Parkinson’s disease, prefrontal fractional anisotropy and caudate nucleus volume partially explained processing speed. For controls, only prefrontal white matter was a significant contributor to processing speed. There were no significant anatomical predictors of working memory for either group.</p><p>Conclusions</p><p>Caudate nuclei volume and prefrontal fractional anisotropy, not frontal gray matter thickness, showed unique and combined significance for processing speed in Parkinson’s disease. Findings underscore the relevance for examining gray-white matter interactions and also highlight clinical processing speed metrics as potential indicators of early cognitive impairment in PD.</p></div

White matter areas with significantly decreased fractional anisotropy (FA) in PD (n = 40) versus non-PD peers (n = 40) corrected with threshold free cluster enhancement.

<p>Areas with significantly decreased FA are shown in colors ranging from red to yellow (p < 0.05, corrected for multiple comparisons). Voxelwise group comparisons of FA were carried out using TBSS (Tract-Based Spatial Statistics, part of FSL). TBSS projects all participants’ FA data onto a mean FA tract skeleton (shown in green), before applying voxelwise cross-subject statistics. MRI conducted within 24 hours of cognitive testing. R = Right; L = Left.</p

Group comparison by neuropsychological domain composite score.

<p>Each composite is based on the average of subtest standardized z-scores derived from published normative references. Average scores range from -0.67 to +0.67. Composite subtest scores are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0147332#pone.0147332.s001" target="_blank">S1 Table</a>.</p

Scatter graphs showing group processing speed composite scores plotted against prefrontal gray thickness, prefrontal white matter fractional anisotropy, and caudate nucleus volume.

<p>The top row shows scatter graphs for the individuals with PD (n = 40). The second row presents the non-PD peers (n = 40). The processing speed composite is based on the average of subtest standardized z-scores derived from published normative references. Note: The referenced r value is r squared.</p