Voxel-based morphometry reveals extra-nigral atrophy patterns associated with dopamine refractory cognitive and motor impairment in parkinsonism
ABSTRACT To determine overall patterns of brain atrophy associated with memory, executive function (EF) and dopamine non-responsive motor measures in older parkinsonian patients.
Forty-three older PD patients (>or=65 years) and matched controls underwent a neurological examination (Unified Parkinson's Disease Rating Scale, separated into dopamine responsive and dopamine non-responsive signs) and neuropsychological testing (memory: California Verbal Learning Test (CVLT)) and a composite of index of executive function (EF): Stroop Interference, Trail Making Test Part B, and digit ordering. All underwent volumetric MRI scans analyzed using voxel-based morphometry (VBM). Group comparisons, and the correlations between MRI gray and white matter volume and motor and cognitive measures were controlled for age, sex and intracranial volume. Cerebellar volume was independently measured using a validated extraction method.
Patients and controls were matched for demographics and global cognitive measures. VBM indicated significant gray matter (GM) atrophy in the cerebellum in PD and was confirmed independently. Poor memory was associated with GM atrophy in the left (uncus, middle temporal and fusiform gyri) and right temporal lobes and left putamen. Dopamine non-responsive motor signs and EF were associated with caudate atrophy. EF was also associated with GM atrophy in the middle temporal gyri, the left precuneus and cerebellum.
Cortical and striatal atrophy were associated with dopamine non-responsive motor signs and cognitive impairment and provide a morphologic correlate for progression of PD. Cerebellar atrophy was found in older PD patients.
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ABSTRACT: Parkinson's disease (PD) and the parkinsonian variant of multiple system atrophy (MSAp) are neurodegenerative disorders that can be difficult to differentiate clinically. This study provides the first characterization of the patterns of task-related functional magnetic resonance imaging (fMRI) changes across the whole brain in MSAp. We used fMRI during a precision grip force task and also performed voxel-based morphometry (VBM) on T1-weighted images in MSAp patients, PD patients, and healthy controls. All groups were matched on age, and the patient groups had comparable motor symptom durations and severities. There were three main findings. First, MSAp and PD had reduced fMRI activation in motor control areas, including the basal ganglia, thalamus, insula, primary sensorimotor and prefrontal cortices, and cerebellum compared with controls. Second, there were no activation differences among the disease groups in the basal ganglia, thalamus, insula, or primary sensorimotor cortices, but PD had more extensive activation deficits throughout the cerebrum compared with MSAp and controls. Third, VBM revealed reduced volume in the basal ganglia, middle and inferior cerebellar peduncles, pons, and throughout the cerebrum in MSAp compared with controls and PD, and additionally throughout the cerebellar cortex and vermis in MSAp compared with controls. Collectively, these results provide the first evidence that fMRI activation is abnormal in the basal ganglia, cerebellum, and cerebrum in MSAp, and that a key distinguishing feature between MSAp and PD is the extensive and widespread volume loss throughout the brain in MSAp.Human Brain Mapping 03/2015; DOI:10.1002/hbm.22694
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ABSTRACT: A growing number of magnetic resonance imaging studies employ voxel-based morphometry (VBM) to assess structural brain changes. Recent reports have shown that image acquisition parameters may influence VBM results. For systematic evaluation, gray-matter-density (GMD) changes associated with aging were investigated by VBM employing acquisitions with different radiofrequency head coils (12-channel matrix coil vs. 32-channel array), different pulse sequences (MP-RAGE vs. MP2RAGE), and different voxel dimensions (1mm vs. 0.8mm). Thirty-six healthy subjects, classified as young, middle-aged, or elderly, participated in the study. Two-sample and paired t-tests revealed significant effects of acquisition parameters (coil, pulse sequence, and resolution) on the estimated age-related GMD changes in cortical and subcortical regions. Potential advantages in tissue classification and segmentation were obtained for MP2RAGE. The 32-channel coil generally outperformed the 12-channel coil, with more benefit for MP2RAGE. Further improvement can be expected from higher resolution if the loss in SNR is accounted for. Use of inconsistent acquisition parameters in VBM analyses is likely to introduce systematic bias. Overall, acquisition and protocol changes require careful adaptations of the VBM analysis strategy before generalized conclusion can be drawn.NeuroImage 11/2013; 87. DOI:10.1016/j.neuroimage.2013.10.051
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ABSTRACT: Parkinson's disease is a chronic progressive neurodegenerative disorder characterized by resting tremor, slowness of movements, rigidity, gait disturbance and postural instability. Most investigations on Parkinson's disease focused on the basal ganglia, whereas the cerebellum has often been overlooked. However, increasing evidence suggests that the cerebellum may have certain roles in the pathophysiology of Parkinson's disease. Anatomical studies identified reciprocal connections between the basal ganglia and cerebellum. There are Parkinson's disease-related pathological changes in the cerebellum. Functional or morphological modulations in the cerebellum were detected related to akinesia/rigidity, tremor, gait disturbance, dyskinesia and some non-motor symptoms. It is likely that the major roles of the cerebellum in Parkinson's disease include pathological and compensatory effects. Pathological changes in the cerebellum might be induced by dopaminergic degeneration, abnormal drives from the basal ganglia and dopaminergic treatment, and may account for some clinical symptoms in Parkinson's disease. The compensatory effect may help maintain better motor and non-motor functions. The cerebellum is also a potential target for some parkinsonian symptoms. Our knowledge about the roles of the cerebellum in Parkinson's disease remains limited, and further attention to the cerebellum is warranted.Brain 03/2013; 136(Pt 3):696-709. DOI:10.1093/brain/aws360