A longitudinal evaluation of personalized intrinsic network topography and cognitive decline in Parkinson's disease.

Resting state functional magnetic resonance imaging (R-fMRI) offers insight into how synchrony within and between brain networks is altered in disease states. Individual and disease-related variability in intrinsic connectivity networks may influence our interpretation of R-fMRI data. We used a personalized approach designed to account for individual variation in the spatial location of correlation maxima to evaluate R-fMRI differences between Parkinson's disease (PD) patients who showed cognitive decline, those who remained cognitively stable and cognitively stable controls. We compared fMRI data from these participant groups, studied at baseline and 18 months later, using both network-based statistics (NBS) and calculations of mean inter- and intra-network connectivity within pre-defined functional networks. The NBS analysis showed that PD participants who remained cognitively stable showed exclusively (at baseline) or predominantly (at follow-up) increased intra-network connectivity, whereas decliners showed exclusively reduced intra-network and inter- (ventral attention and default mode) connectivity, in comparison with the control group. Evaluation of mean connectivity between all regions of interest (ROIs) within a priori networks showed that decliners had consistently reduced inter-network connectivity for ventral attention, somatomotor, visual and striatal networks and reduced intra-network connectivity for ventral attention network to striatum and cerebellum. These findings suggest that specific functional connectivity covariance patterns differentiate PD cognitive subtypes and may predict cognitive decline. Further, increased intra and inter-network synchrony may support cognitive function in the face of PD-related network disruptions.

Cerebral cortical thickness and cognitive decline in Parkinson's disease.

In Parkinson's disease (PD), reduced cerebral cortical thickness may reflect network-based degeneration. This study performed cognitive assessment and brain MRI in 30 PD participants and 41 controls at baseline and 18 months later. We hypothesized that cerebral cortical thickness and volume, as well as change in these metrics, would differ between PD participants who remained cognitively stable and those who experienced cognitive decline. Dividing the participant sample into PD-stable, PD-decline, and control-stable groups, we compared mean cortical thickness and volume within segments that comprise the prefrontal cognitive-control, memory, dorsal spatial, and ventral object-based networks at baseline. We then compared the rate of change in cortical thickness and volume between the same groups using a vertex-wise approach. We found that the PD-decline group had lower cortical thickness within all 4 cognitive networks in comparison with controls, as well as lower cortical thickness within the prefrontal and medial temporal networks in comparison with the PD-stable group. The PD-decline group also experienced a greater rate of volume loss in the lateral temporal cortices in comparison with the control group. This study suggests that lower thickness and volume in prefrontal, medial, and lateral temporal regions may portend cognitive decline in PD.

Cross-sectional and longitudinal associations between total and regional white matter hyperintensity volume and cognitive and motor function in Parkinson's disease.

BACKGROUND: White matter hyperintensities (WMH) are frequently observed on T2-weighted brain magnetic resonance imaging studies of healthy older adults and have been linked with impairments in balance, gait, and cognition. Nonetheless, few studies have investigated the longitudinal effects of comorbid WMH on cognition and motor function in Parkinson's disease. METHODS: The Lesion Segmentation Tool for Statistical Parametric Mapping was used to obtain total lesion volume and map regional WMH probabilities in 29 PD and 42 control participants at two study visits 18 months apart. Both cross-sectional and longitudinal comparisons were made between composite scores in the domains of executive function, memory, and language, and Unified Parkinson's Disease Rating Scale (UPDRS) scores. RESULTS: We found no difference between disease and control groups in total WMH volume or progression during the study. Greater regional and global WMH at baseline was more strongly associated with lower executive function in PD subjects than in controls. Increased regional WMH was also more strongly associated with impaired memory performance in PD relative to controls. Longitudinally, no associations between cognitive change and total or regional WMH progression were detected in either group. A positive relationship between baseline regional WMH and total UPDRS scores was present in the control group, but not PD. However, greater WMH increase was associated with a greater increase in UPDRS motor sub-scores in PD. CONCLUSIONS: These findings suggest that although PD patients do not experience greater mean WMH load than normal aged adults, comorbid WMH do exacerbate cognitive and motor symptoms in PD.

Arterial spin labeling reveals relationships between resting cerebral perfusion and motor learning in Parkinson's disease.

Parkinson's disease (PD) is an age-related neurodegenerative disease that produces changes in movement, cognition, sleep, and autonomic function. Motor learning involves acquisition of new motor skills through practice, and is affected by PD. The purpose of the present study was to evaluate regional differences in resting cerebral blood flow (rCBF), measured using arterial spin labeling (ASL) MRI, during a finger-typing task of motor skill acquisition in PD patients compared to age- and gender-matched controls. Voxel-wise multiple linear regression models were used to examine the relationship between rCBF and several task variables, including initial speed, proficiency gain, and accuracy. In these models, a task-by-disease group interaction term was included to investigate where the relationship between rCBF and task performance was influenced by PD. At baseline, perfusion was lower in PD subjects than controls in the right occipital cortex. The task-by-disease group interaction for initial speed was significantly related to rCBF (p < 0.05, corrected) in several brain regions involved in motor learning, including the occipital, parietal, and temporal cortices, cerebellum, anterior cingulate, and the superior and middle frontal gyri. In these regions, PD patients showed higher rCBF, and controls lower rCBF, with improved performance. Within the control group, proficiency gain over 12 typing trials was related to greater rCBF in cerebellar, occipital, and temporal cortices. These results suggest that higher rCBF within networks involved in motor learning enable PD patients to compensate for disease-related deficits.

Longitudinal white matter microstructural change in Parkinson's disease.

Postmortem studies of Parkinson's disease (PD) suggest that Lewy body pathology accumulates in a predictable topographical sequence, beginning in the olfactory bulb, followed by caudal brainstem, substantia nigra, limbic cortex, and neocortex. Diffusion-weighted imaging (DWI) is sensitive, if not specific, to early disease-related white matter (WM) change in a variety of traumatic and degenerative brain diseases. Although numerous cross-sectional studies have reported DWI differences in cerebral WM in PD, only a few longitudinal studies have investigated whether DWI change exceeds that of normal aging or coincides with regional Lewy body accumulation. This study mapped regional differences in the rate of DWI-based microstructural change between 29 PD patients and 43 age-matched controls over 18 months. Iterative within- and between-subject tensor-based registration was completed on motion- and eddy current-corrected DWI images, then baseline versus follow-up difference maps of fractional anisotropy, mean, radial, and axial diffusivity were analyzed in the Biological Parametric Mapping toolbox for MATLAB. This analysis showed that PD patients had a greater decline in WM integrity in the rostral brainstem, caudal subcortical WM, and cerebellar peduncles, compared with controls. In addition, patients with unilateral clinical signs at baseline experienced a greater rate of WM change over the 18-month study than patients with bilateral signs. These findings suggest that rate of WM microstructural change in PD exceeds that of normal aging and is maximal during early stage disease. In addition, the neuroanatomic locations (rostral brainstem and subcortical WM) of accelerated WM change fit with current theories of topographic disease progression.

Predictors of common femoral artery access site complications in patients on oral anticoagulants and undergoing a coronary procedure.

BACKGROUND: It is unclear whether patients on oral anticoagulants (OAC) undergoing a procedure using common femoral artery access have higher adverse events when compared to patients who are not anticoagulated at the time of the procedure. METHODS: We retrospectively reviewed data from consecutive patients who underwent a cardiac procedure at a tertiary medical center. Patients were considered (group A) fully or partially anticoagulated if they had an international normalized ratio (INR) ≥1.6 on the day of the procedure or were on warfarin or new OAC within 48 h and 24 h of the procedure, respectively. The nonanticoagulated group (group B) had an INR <1.6 or had stopped their warfarin and new OAC >48 h and >24 h preprocedure, respectively. The index primary end point of the study was defined as the composite end point of major bleeding, vascular complications, or cardiovascular-related death during index hospitalization. The 30-day primary end point was defined as the occurrence of the index primary end point and up to 30 days postprocedure. RESULTS: A total of 779 patients were included in this study. Of these patients, 27 (3.5%) patients were in group A. The index primary end point was met in 11/779 (1.4%) patients. The 30-day primary composite end point was met in 18/779 (2.3%) patients. There was no difference in the primary end point at index between group A (1/27 [3.7%]) and group B (10/752 [1.3%]; P=0.3155) and no difference in the 30-day primary composite end point between group A (2/27 [7.4%]) and group B (16/752 [2.1%]; P=0.1313). Multivariable analysis showed that a low creatinine clearance (odds ratio [OR] =0.56; P=0.0200) and underweight patients (<60 kg; OR =3.94; P=0.0300) were independent predictors of the 30-day primary composite end point but not oral anticoagulation (P=0.1500). CONCLUSION: Patients on OAC did not have higher 30-day major adverse events than those who were not anticoagulated at index procedure.