Assessment of cortical degeneration in patients with Parkinson's disease by voxel-based morphometry, cortical folding, and cortical thickness

Noninvasive brain imaging methods provide useful information on cerebral involution and degenerative processes. Here we assessed cortical degeneration in 20 nondemented patients with Parkinson's disease (PD) and 20 healthy controls using three quantitative neuroanatomical approaches: voxel‐based morphometry (VBM), cortical folding (BrainVisa), and cortical thickness (FreeSurfer). We examined the relationship between global and regional gray matter (GM) volumes, sulcal indices, and thickness measures derived from the previous methods as well as their association with cognitive performance, age, severity of motor symptoms, and disease stage. VBM analyses showed GM volume reductions in the left temporal gyrus in patients compared with controls. Cortical folding measures revealed significant decreases in the left frontal and right collateral sulci in patients. Finally, analysis of cortical thickness showed widespread cortical thinning in right lateral occipital, parietal and left temporal, frontal, and premotor regions. We found that, in patients, all global anatomical measures correlated with age, while GM volume and cortical thickness significantly correlated with disease stage. In controls, a significant association was found between global GM volume and cortical folding with age. Overall these results suggest that the three different methods provide complementary and related information on neurodegenerative changes occurring in PD, however, surface‐based measures of cortical folding and especially cortical thickness seem to be more sensitive than VBM to identify regional GM changes associated to PD. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.     

Widespread cortical and subcortical brain atrophy in Parkinson’s disease with excessive daytime sleepiness

Our aim was to determine regional brain atrophy in Parkinson’s disease (PD) patients with excessive daytime sleepiness (EDS) using voxel-based morphometry (VBM). From 71 consecutive probable PD patients, nine non-demented and non-hallucinating patients with an Epworth Sleepiness Scale (ESS) ≥ 10 and 13 PD patients with an ESS ≤ 3 were selected as having EDS and as not having EDS, respectively. We also enrolled 22 healthy age- and sex-matched controls. Regional brain atrophy was assessed using VBM with 3-T magnetic resonance imaging. There was no difference in the dosage of dopaminergic drugs between PD patients with EDS and PD patients without EDS. PD patients with EDS showed marked atrophy in the gray matter of the frontal lobe, temporal lobe, occipital lobe, limbic lobe including the nucleus basalis of Meynert compared to controls (false discovery rate corrected p < 0.05). In contrast, PD patients without EDS did not show any significant difference in gray matter atrophy compared to controls (false discovery rate corrected p < 0.05). PD patients with EDS showed significant atrophy of the frontal lobe, temporal lobe, occipital lobe, limbic lobe including the nucleus basalis of Meynert compared to PD patients without EDS (uncorrected p < 0.001). PD patients with EDS, even without dementia and hallucination, showed significant gray matter atrophy compared to PD patients without EDS and controls.     

Frontal functional connectivity and disease duration interactively predict cognitive decline in Parkinson's disease

ObjectiveCognitive decline does not always follow a predictable course in Parkinson’s disease (PD), with some patients remaining stable while others meet criteria for dementia from early stages. Functional connectivity has been proposed as a good correlate of cognitive decline in PD, although it has not been explored whether the association between this connectivity and cognitive ability is influenced by disease duration, which was our objective.MethodsWe included 30 patients with PD and 15 healthy controls (HC). Six cognitive domains were estimated based on neuropsychological assessment. Phase-based connectivity at frontal and posterior cortical regions was estimated from a resting EEG.ResultsThe PD group showed significant impairment for the executive, visuospatial, and language domains compared with HC. Increased connectivity at frontal regions was also found in the PD group. Frontal delta and theta connectivity negatively influenced general cognition and visuospatial performance, but this association was moderated by disease duration, with increased connectivity predicting worse performance after 8 years of disease duration.ConclusionSubtle neurophysiological changes underlie cognitive decline along PD progression, especially around a decade after motor symptoms onset.SignificanceConnectivity of EEG slow waves at frontal regions might be used as a predictor of cognitive decline in PD.     

Hierarchical cluster analysis of multimodal imaging data identifies brain atrophy and cognitive patterns in Parkinson’s disease

BackgroundParkinson's disease (PD) is a heterogeneous condition. Cluster analysis based on cortical thickness has been used to define distinct patterns of brain atrophy in PD. However, the potential of other neuroimaging modalities, such as white matter (WM) fractional anisotropy (FA), which has also been demonstrated to be altered in PD, has not been investigated.ObjectiveWe aim to characterize PD subtypes using a multimodal clustering approach based on cortical and subcortical gray matter (GM) volumes and FA measures.MethodsWe included T1-weighted and diffusion-weighted MRI data from 62 PD patients and 33 healthy controls. We extracted mean GM volumes from 48 cortical and 17 subcortical regions using FSL-VBM, and the mean FA from 20 WM tracts using Tract-Based Spatial Statistics (TBSS). Hierarchical cluster analysis was performed with the PD sample using Ward's linkage method. Whole-brain voxel-wise intergroup comparisons of VBM and TBSS data were also performed using FSL. Neuropsychological and demographic statistical analyses were conducted using IBM SPSS Statistics 25.0.ResultsWe identified three PD subtypes, with prominent differences in GM patterns and little WM involvement. One group (n = 15) with widespread cortical and subcortical GM volume and WM FA reductions and pronounced cognitive deficits; a second group (n = 21) with only cortical atrophy limited to frontal and temporal regions and more specific neuropsychological impairment, and a third group (n = 26) without detectable atrophy or cognition impairment.ConclusionMultimodal MRI data allows classifying PD patients into groups according to GM and WM patterns, which in turn are associated with the cognitive profile.     

Perfusion ECD/SPECT in the characterization of cognitive deficits in Parkinson's disease

Cognitive abnormalities have been reported in a large percentage of patients with Parkinson's disease (PD). Often cognitive changes are sub-clinical and involve frontal lobe function. In other occasions they develop into full dementia. Functional neuroimaging may help characterize these abnormalities. We have studied brain perfusion with SPECT and the tracer ECD in 44 PD patients, 22 presenting with normal cognitive function and 22 with clinical and neuropsychological signs of dementia. Compared with 21 healthy controls, demented PD patients showed significant perfusion decrements in all cortical areas, particularly temporal and parietal regions; in the non-demented cohort reductions were limited to the frontal lobe area. These results suggest that brain perfusion abnormalities are present in PD patients. It is speculated that different pathological mechanisms underlie perfusion differences.     

Olfactory performance acts as a cognitive reserve in non-demented patients with Parkinson's disease

ObjectiveTo explore whether olfactory performance acts as a cognitive reserve in non-demented patients with Parkinson's disease (PD).MethodsPatients with non-demented PD (n = 119) underwent T1-weighted MRI and olfactory identification tests. According to their olfactory performance, PD patients were subdivided into three groups of high score (PD-H, n = 38), middle score (PD-M, n = 48), and low score (PD-L, n = 33). We investigated the pattern of gray matter (GM) density according to olfactory performance using voxel-based morphometry (VBM) and analyzed the correlation between GM density and olfactory performance.ResultsNo significant differences in demographic characteristics were observed among the groups. A neuropsychological test showed that cognitive deficits in verbal memory function were more severe in the PD-L group than in the PD-H group. However, a VBM analysis revealed that patients in the PD-H group possessed significantly decreased GM density in the bilateral temporal areas, orbitofrontal areas, mesiofrontal areas extending into the cingulate gyrus, and prefrontal areas, compared with patients in the PD-L group. No areas exhibiting a significant difference in GM density were observed between the PD-H and PD-M groups. Olfactory performance in patients with PD was negatively correlated with both the brain GM volume and intracerebral volume; in particular, GM density in the caudate nucleus and putamen exhibited a negative correlation with olfactory performance.ConclusionsOur data show that a high olfactory performance may compensate GM volume loss in order to minimize the exhibition of cognitive impairment and thus may act as a cognitive reserve in non-demented patients with PD.     

Cognitive profiling in relation to short latency afferent inhibition of frontal cortex in multiple system atrophy

BackgroundCognitive dysfunction occurs in multiple system atrophy (MSA) more frequently than previously known. As a type of synucleinopathy, pathology spreads widely in cortical and subcortical areas as the disease advances. The exact anatomical and imaging substrates, and electrophysiological or biochemical indicators of cognitive impairment in MSA are not yet clear. Diminished short-latency afferent inhibition (SAI) of motor cortex was shown to be an electrophysiological correlate of dementia and mild cognitive impairment associated to Parkinson's disease (PD). We hypothesize that it can also be electrophysiological correlate of cognitive impairment in MSA.MethodsWe studied SAI and a neuropsychological test battery in 19 non-demented MSA patients (11 MSA-P and 8 MSA-C), 10 non-demented PD patients and 10 healthy controls. Neuropsychological test scores were grouped in four main cognitive domains (attention, memory, executive and visuo-spatial functions) and were analyzed by factor analysis.ResultsAll subject groups were matched for age. Moreover, the MSA-P, MSA-C, and PD groups were matched for disease duration. Scores of cognitive domains were similar in MSA and PD cases, while scores in attention, executive and visuo-spatial domains were worse in MSA than controls (p < 0.05). SAI was normal in PD but decreased in MSA patients by reaching statistical significance in MSA-C subtype. SAI response was correlated with cognitive performances measured by factor scores of neuropsychological test battery in all study subjects.ConclusionsThese results show that cognitive functions are impaired in MSA patients compared to controls as well as a parallel reduction in SAI response.     

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

ObjectivesTo determine overall patterns of brain atrophy associated with memory, executive function (EF) and dopamine non-responsive motor measures in older parkinsonian patients.DesignForty-three older PD patients (≥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.ResultsPatients 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.ConclusionsCortical 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.     

Neural correlates of minor hallucinations in non-demented patients with Parkinson's disease

BackgroundHallucinations are a frequent and severe complication in Parkinson's disease (PD). Minor hallucinations are generally not disturbing, but likely progress to well-structured hallucinations with loss of insight and a great impact on quality of life. Knowledge on the neural bases of minor hallucinations may help to describe those systems associated with the early development of psychotic phenomena in PD.In this study, we aimed to identify the pattern of structural brain alterations associated with minor hallucinations in PD by using voxel-based morphometry (VBM).MethodsWe prospectively collected a sample of 46 non-demented PD patients, with (N = 17) and without (n = 29) minor hallucinations (passage and/or presence hallucinations), and 15 healthy controls. Groups were matched for age, education and global cognitive function. Presence and type of minor psychotic phenomena was assessed by the new MDS-UPDRS. Three dimensional T1-weighted MRI images were acquired with a 1.5 T magnet, and analyzed using optimized VBM.ResultsCompared to controls, PD with minor hallucinations (PD-mH) showed reduced gray matter volume bilaterally in different areas of the dorsal visual stream, and in functionally related midbrain and cerebellar structures. Additionally, bilateral gray matter volume increases were observed in the PD-mH group in limbic and paralimbic regions.ConclusionsOur data support a major role of the dorsal visual stream in the genesis of minor hallucinations in PD, reinforcing the importance of posterior cortical regions for the development of cognitive and psychiatric complications in PD.     

A combined tract-based spatial statistics and voxel-based morphometry study of the first MRI scan after diagnosis of amyotrophic lateral sclerosis with subgroup analysis

Background and purpose

This study aims to compare the cortical and subcortical deep gray matter (GM) and white matter (WM) of ALS subjects and controls and to compare ALS subjects with (ALScog) and without (ALSnon-cog) cognitive impairment.

Exploring cortical atrophy and its clinical and biochemical correlates in Wilson’s disease using voxel based morphometry

ObjectivesTo determine cortical grey matter (GM) changes and their clinical and biochemical correlates in patients with Wilson’s disease using voxel based morphometry (VBM).MethodsClinical and imaging data of 10 patients (all male, mean age 16.0 ± 6.3years) with Wilson’s Disease were analyzed. T1W volumetric MRI data of patients without obvious cortical atrophy or signal changes on conventional MRI was compared with MRI of 11 matched control subjects using VBM analysis with Statistical Parametric Mapping 8. Results were expressed at statistical threshold of p < 0.05 (FWE corrected) and p < 0.001 (uncorrected). Multiple regression analysis was done to analyze possible relation between GM atrophy, duration of disease and biochemical abnormalities.ResultsCompared to controls, patients showed scattered areas of reduced GM volume in bilateral caudate head, medial part of right globus pallidus and body of right caudate (FWE corrected p < 0.05). At p < 0.001(uncorrected) widespread areas of cortical atrophy were also noted involving the frontal and temporal lobes, lentiform nuclei, cerebellum and thalamus. Significant positive correlation (uncorrected p < 0.001) were noted between (i) duration of disease and cortical GM volume of frontal, parietal and temporal lobes and cerebellum (ii) serum copper levels and GM volume of right medial frontal gyrus and paracentral lobule.ConclusionsTo the best of our knowledge, this is the first VBM study in patients with Wilson’s disease. In spite of apparently normal cortex on visual inspection of MRI, decreased cortical GM volume was detected using VBM. In addition, serum copper may act as surrogate marker of cortical abnormalities in Wilson’s disease.     

Altered speech-related cortical network in frontotemporal dementia

BackgroundIn healthy subjects (HS), transcranial magnetic stimulation (TMS) demonstrated an increase in motor-evoked potential (MEP) amplitudes during specific linguistic tasks. This finding indicates functional connections between speech-related cortical areas and the dominant primary motor cortex (M1).ObjectiveTo investigate M1 function with TMS and the speech-related cortical network with neuroimaging measures in frontotemporal dementia (FTD), including the non-fluent variant of primary progressive aphasia (nfv-PPA) and the behavioral variant of FTD (bv-FTD).MethodsM1 excitability changes during specific linguistc tasks were examined using TMS in 24 patients (15 with nfv-PPA and 9 with bv-FTD) and in 18 age-matched HS. In the same patients neuroimaging was used to assess changes in specific white matter (WM) bundles and grey matter (GM) regions involved in language processing, with diffusion tensor imaging (DTI) and voxel-based morphometry (VBM).ResultsDuring the linguistic task, M1 excitability increased in HS, whereas in FTD patients it did not. M1 excitability changes were comparable in nfv-PPA and bv-FTD. DTI revealed decreased fractional anisotropy in the superior and inferior longitudinal and uncinate fasciculi. Moreover, VBM disclosed GM volume loss in the left frontal operculum though not in the parietal operculum or precentral gyrus. Furthermore, WM and GM changes were comparable in nfv-PPA and bv-FTD. There was no correlation between neurophysiological and neuroimaging changes in FTD. Atrophy in the left frontal operculum correlated with linguistic dysfunction, assessed by semantic and phonemic fluency tests.ConclusionWe provide converging neurophysiological and neuroimaging evidence of abnormal speech-related cortical network activation in FTD.     

Gray matter correlates of dopaminergic degeneration in Parkinson's disease: A hybrid PET/MR study using 18F‐FP‐CIT

Dopaminergic degeneration is a hallmark of Parkinson's disease (PD), which causes various symptoms affected by corticostriatal circuits. So far, the relationship between cortical changes and dopamine loss in the striatum is unclear. Here, we evaluate the gray matter (GM) changes in accordance with striatal dopaminergic degeneration in PD using hybrid PET/MR. Sixteen patients with idiopathic PD underwent ¹⁸F‐FP‐CIT PET/MR. To measure dopaminergic degeneration in PD, binding ratio (BR) of dopamine transporter in striatum was evaluated by ¹⁸F‐FP‐CIT. Voxel‐based morphometry (VBM) was used to evaluate GM density. We obtained voxelwise correlation maps of GM density according to the striatal BR. Voxel‐by‐voxel correlation between BR maps and GM density maps was done to evaluate region‐specific correlation of striatal dopaminergic degeneration. There was a trend of positive correlation between striatal BR and GM density in the cerebellum, parahippocampal gyri, and frontal cortex. A trend of negative correlation between striatal BR and GM density in the medial occipital cortex was found. Voxel‐by‐voxel correlation revealed that the positive correlation was mainly dependent on anterior striatal BR, while posterior striatal BR mostly showed negative correlation with GM density in occipital and temporal cortices. Decreased GM density related to anterior striatal dopaminergic degeneration might demonstrate degeneration of dopaminergic nonmotor circuits. Furthermore, the negative correlation could be related to the motor circuits of posterior striatum. Our integrated PET/MR study suggests that the widespread structural progressive changes in PD could denote the cortical functional correlates of the degeneration of striatal dopaminergic circuits. Hum Brain Mapp 37:1710–1721, 2016. © 2016 Wiley Periodicals, Inc .     

Mild cognitive impairment in patients with Parkinson's disease is associated with increased cortical degeneration

Mild cognitive impairment (MCI) can occur early in the course of Parkinson's disease (PD), and its presence increases the risk of developing dementia. Determining the cortical changes associated with MCI in PD, thus, may be useful in predicting the future development of dementia. To address this objective, 37 patients with PD, divided into 2 groups according to the presence or absence MCI (18 with and 19 without) and 16 matched controls, underwent anatomic magnetic resonance imaging. Corticometry analyses were performed to measure the changes in cortical thickness and surface area as well as their correlation with disease duration. Compared with healthy controls, the PD‐MCI group exhibited increased atrophy and changes of local surface area in the bilateral occipital, left temporal, and frontal cortices; whereas the PD non‐MCI group exhibited only unilateral thinning and decreased surface area in the occipital lobe and in the frontal cortex. In addition, a comparison between the PD‐MCI and PD non‐MCI groups revealed increased local surface area in the occipital lobe, temporal lobe, and postcentral gyrus for the cognitively impaired patients. It is noteworthy that, in the PD‐MCI group, cortical thickness had a significant negative correlation with disease duration in the precentral, supramarginal, occipital, and superior temporal cortices; whereas, in the PD non‐MCI group, such a correlation was absent. The findings from this study reveal that, at the same stage of PD evolution, the presence of MCI is associated with a higher level of cortical changes, suggesting that cortical degeneration is increased in patients with PD because of the presence of MCI. © 2013 International Parkinson and Movement Disorder Society     

Gray Matter Abnormalities in Idiopathic Parkinson's Disease: Evaluation by Diffusional Kurtosis Imaging and Neurite Orientation Dispersion and Density Imaging

Mapping gray matter (GM) pathology in Parkinson's disease (PD) with conventional MRI is challenging, and the need for more sensitive brain imaging techniques is essential to facilitate early diagnosis and assessment of disease severity. GM microstructure was assessed with GM‐based spatial statistics applied to diffusion kurtosis imaging (DKI) and neurite orientation dispersion imaging (NODDI) in 30 participants with PD and 28 age‐ and gender‐matched controls. These were compared with currently used assessment methods such as diffusion tensor imaging (DTI), voxel‐based morphometry (VBM), and surface‐based cortical thickness analysis. Linear discriminant analysis (LDA) was also used to test whether subject diagnosis could be predicted based on a linear combination of regional diffusion metrics. Significant differences in GM microstructure were observed in the striatum and the frontal, temporal, limbic, and paralimbic areas in PD patients using DKI and NODDI. Significant correlations between motor deficits and GM microstructure were also noted in these areas. Traditional VBM and surface‐based cortical thickness analyses failed to detect any GM differences. LDA indicated that mean kurtosis (MK) and intra cellular volume fraction (ICVF) were the most accurate predictors of diagnostic status. In conclusion, DKI and NODDI can detect cerebral GM abnormalities in PD in a more sensitive manner when compared with conventional methods. Hence, these methods may be useful for the diagnosis of PD and assessment of motor deficits. Hum Brain Mapp 38:3704–3722, 2017. © 2017 Wiley Periodicals, Inc.     

Motor and extra-motor gray matter integrity may underlie neurophysiologic parameters of motor function in amyotrophic lateral sclerosis: a combined voxel-based morphometry and transcranial stimulation study

The association between gray matter (GM) density and neurophysiologic changes is still unclear in amyotrophic lateral sclerosis (ALS). We evaluated the relationship between GM density and motor system integrity combining voxel-based morphometry (VBM) and transcranial magnetic stimulation (TMS) in ALS. We included 17 ALS patients and 22 healthy controls (HC) who underwent 3D-T1-weighted imaging. Among the ALS group, we applied left motor cortex single-pulse TMS. We used whole-brain VBM comparing ALS and HC in GM density. We also conducted regression analysis to examine correlations between GM density and the following TMS parameters: motor evoked potential (MEP)/M ratio and central motor conduction time (CMCT). We found significantly decreased GM density in ALS patients in several frontal, temporal, parietal/occipital and cerebellar regions (p?<?0.001 uncorrected; cluster-extent threshold k?=?100 voxels per cluster). With regards to TMS parameters, ALS patients showed mostly increased MEP/M ratio and modest prolongation of CMCT. MEP/M ratio was associated with GM density in (a) rolandic operculum/inferior frontal gyrus/precentral gyrus; anterior cingulate gyrus; inferior temporal gyrus; superior parietal lobule; cuneus; superior occipital gyrus and cerebellum (positive association) and (b) paracentral lobule/supplementary motor area (negative association). CMCT was associated with GM density in (a) inferior frontal gyrus and middle cingulated gyrus (positive association) and (b) superior parietal lobule; cuneus and cerebellum (negative association). Our findings support a significant interaction between motor and extra-motor structural and functional changes and highlight that motor and extra-motor GM integrity may underlie TMS parameters of motor function in ALS patients.     

Structural and functional evaluation of cortical motor areas in Amyotrophic Lateral Sclerosis

The structural and functional data gathered with Magnetic Resonance Imaging (MRI) techniques about the brain cortical motor damage in Amyotrophic Lateral Sclerosis (ALS) are controversial. In fact some structural MRI studies showed foci of gray matter (GM) atrophy in the precentral gyrus, even in the early stage, while others did not. Most functional MRI (fMRI) studies in ALS reported hyperactivation of extra-primary motor cortices, while contradictory results were obtained on the activation of the primary motor cortex. We aimed to investigate the cortical motor circuitries in ALS patients by a combined structural and functional approach. Twenty patients with definite ALS and 16 healthy subjects underwent a structural examination with acquisition of a 3D T1-weighted sequence and fMRI examination during a maximal force handgrip task executed with the right-hand, the left-hand and with both hands simultaneously. The T1-weighted images were analyzed with Voxel-Based Morphometry (VBM) that showed several clusters of reduced cortical GM in ALS patients compared to controls including the pre and postcentral gyri, the superior, middle and inferior frontal gyri, the supplementary motor area, the superior and inferior parietal cortices and the temporal lobe, bilaterally but more extensive on the right side. In ALS patients a significant hypoactivation of the primary sensory motor cortex and frontal dorsal premotor areas as compared to controls was observed. The hypoactivated areas matched with foci of cortical atrophy demonstrated by VBM. The fMRI analysis also showed an enhanced activation in the ventral premotor frontal areas and in the parietal cortex pertaining to the fronto-parietal motor circuit which paralleled with disease progression rate and matched with cortical regions of atrophy. The hyperactivation of the fronto-parietal circuit was asymmetric and prevalent in the left hemisphere. VBM and fMRI identified structural and functional markers of an extended cortical damage within the motor circuit of ALS patients. The functional changes in non-primary motor cortices pertaining to fronto-parietal circuit suggest an over-recruitment of a pre-existing physiological sensory-motor network. However, the concomitant fronto-parietal cortical atrophy arises the possibility that such a hyper-activation reflects cortical hyper-excitability due to loss of inhibitory inter-neurons.     

A novel bedside task to tap inhibitory dysfunction and fronto-striatal atrophy in Parkinson's disease

BackgroundGiven the heterogeneity of mild cognitive deficits in non-demented Parkinson's disease (PD), sensitive and anatomically specific behavioural measures are crucial when evaluating cognition in this patient group. Inhibitory dysfunction is one such deficit increasingly being recognised in non-demented PD; however, few clinical measures exist to detect it and its associated fronto-striatal pathology.MethodsIn 50 non-demented PD patients and 27 controls we employ a novel measure, the Excluded Letter Fluency (ELF) test, to objectively assess inhibitory dysfunction. ELF results were also contrasted with an established inhibitory measure (Hayling Test) and covaried against grey matter atrophy via voxel-based morphometry analysis in a subset of patients.ResultsThe findings show that patients made significantly more rule-break errors than controls on the ELF and this measure was more sensitive than the Hayling in detecting inhibitory dysfunction, classifying over 76% of patients in logistic regression analysis. Importantly, ELF rule-break errors correlated with grey matter atrophy in known inhibitory-control regions (orbitofrontal cortex, inferior frontal gyrus and ventral striatum).ConclusionsThe ELF is a brief bedside task that efficiently detects inhibitory dysfunction in non-demented PD. The utility of this novel behavioural measure is further substantiated by its anatomical specificity for fronto-striatal inhibitory control regions.     

[C]PIB-, [F]FDG-PET and MRI imaging in patients with Parkinson’s disease with and without dementia

The objective of this study was to identify possible group differences between PD patients with dementia and without dementia by combining different functional and structural imaging methods in vivo, which might provide an opportunity to disentangle the pathophysiological correlates of cognitive impairment and dementia in PD. We performed a neuropsychological evaluation, structural brain MRI, [¹⁸F]FDG PET and [¹¹C]PIB PET in 19 PD patients [eight non-demented (PD), eleven demented (PDD)] and 24 healthy elderly volunteers. [¹¹C]PIB region-to-cerebellum ratios did not differ significantly between the groups in any brain region (p > 0.05). PDD patients showed impaired glucose metabolism in cortical brain regions and this reduction was associated with the degree of cognitive impairment. PDD patients had more atrophy both in the hippocampus and the frontal cortex compared with PD patients and controls, and hippocampal atrophy was associated with impaired memory. This cross-sectional data suggests that development of dementia in PD is associated with extensive spread of hypometabolism beyond the occipital cortex, and with hippocampal and frontal atrophy but not beta-amyloid deposition consistent with a unique biological process related to PD rather than co-incidental development of AD in persons with PD.     

Marked N-acetylaspartate and choline metabolite changes in Parkinson's disease patients with mild cognitive impairment

BackgroundThe mild cognitive impairment in Parkinson's disease (PD-MCI) has received increasing attention, of which the diagnosis is challenging. To analyze the possible biomarkers for the early diagnosis, we investigated the metabolite changes in different brain regions of PD-MCI patients as well as appropriate controls by proton magnetic resonance spectroscopy (MRS).MethodsThe metabolism in the occipital lobe, posterior cingulate, substantia nigra and basal ganglia was studied in 66 PD-MCI patients, 70 cognitively normal PD patients (PD-CN) and 74 healthy controls.ResultsThe N-acetylaspartate to creatine (NAA/Cr) ratio in the occipital lobe in PD-MCI patients was lower than that in healthy controls (P < 0.05). In contrast, the choline to creatine ratio in the posterior cingulate was higher in PD-MCI patients than in controls or PD-CN patients (both P < 0.05). No significant metabolite difference in the substantia nigra and basal ganglia was found. Furthermore, the decreases of the ratios of NAA/Cr in the occipital lobe were associated with PD-CN (P < 0.05) and PD-MCI (P < 0.0001) while the increase in the ratio of Cho/Cr in the posterior cingulate was associated with PD-MCI (P ≤ 0.01).ConclusionThe metabolite changes in the occipital lobe and posterior cingulate occur in the early cognitive impairment phase of PD patients. Such variations can be used as the marker for the detection of PD-MCI.