Voxel-based morphometry reveals extra-nigral atrophy patterns associated with dopamine refractory cognitive and motor impairment in Parkinsonism

Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
Parkinsonism & Related Disorders (Impact Factor: 3.97). 07/2008; 15(3):187-95. DOI: 10.1016/j.parkreldis.2008.05.002
Source: PubMed


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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    • "In contrast , most VBM studies in cognitively intact PD have reported no significant volumetric changes [Beyer et al., 2007; Brenneis et al., 2003; Dalaker et al., 2010; Melzer et al., 2012; Menke et al., 2014; Price et al., 2004; Prodoehl et al., 2013; Tessitore et al., 2012] or reduced volume in only a few areas that vary across studies [Camicioli et al., 2009; Cordato et al., 2005; Martin et al., 2009; Nagano-Saito et al., 2005; Pereira et al., 2012; Summerfield et al., 2005; Tir et al., 2009]. To date, no studies in MSAp and only one in PD have normalized VBM data to a cerebellum-specific template [Camicioli et al., 2009], thus making it unclear how the macrostructure of this important motor control area is affected in these diseases. "
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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 · 5.97 Impact Factor
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    • "Thirty-two studies were identified in the meta-analysis (Figure 1) and a total of 24 studies on PD were included (Burton et al., 2004; Cordato et al., 2005; Nagano-Saito et al., 2005; Beyer et al., 2007; Ramirez-Ruiz et al., 2007; Feldmann et al., 2008; Karagulle Kendi et al., 2008; Camicioli et al., 2009; Jubault et al., 2009; Martin et al., 2009; Pereira et al., 2009; Sanchez-Castaneda et al., 2009; Tir et al., 2009; Dalaker et al., 2010; Kostic et al., 2010; Lee et al., 2010; Cerasa et al., 2011; Focke et al., 2011; Meppelink et al., 2011; Compta et al., 2012; Fernández-Seara et al., 2012; Hong et al., 2012; Ibarretxe-Bilbao et al., 2012; Tessitore et al., 2012). Seven hundred and sixteen PD patients and 535 HC subjects met the inclusion criteria for meta-analysis. "
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    Frontiers in Human Neuroscience 02/2014; 8(1):63. DOI:10.3389/fnhum.2014.00063 · 3.63 Impact Factor
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    • "The caudate body is also involved in motor coordination, and is one of the main regions of atrophy underlying degenerative motor impairment [39]. In a similar vein, smaller caudate volume in our Val elderly carriers predicted slower motor responses on the working memory task, thus BDNF-related deficits may specifically target dopaminergic neurons in the caudate in the elderly, leading to motor impairment. "
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