Non-depressed Parkinson's Disease Research Articles

Altered functional-structural coupling may predict Parkinson's patient's depression.

We aimed to elucidate the neurobiological basis of depression in Parkinson's disease and identify potential imaging markers for depression in patients with Parkinson's disease. We recruited 43 normal controls (NC), 46 depressed Parkinson's disease patients (DPD) and 56 non-depressed Parkinson's disease (NDPD). All participants underwent routine T2-weighted, T2Flair, and resting-state scans on the same 3.0T magnetic resonance imaging (MRI) scanner at our hospital. Pre-processing includes calculating surface-based Regional Homogeneity (2DReHo) and cortical thickness. Then we defined the correlation coefficient between 2DReHo and cortical thickness as the functional-structural coupling index. Between-group comparisons were conducted on the Fisher's Z-transformed correlation coefficients. To identify specific regions of decoupling, the 2DReHo for each participant were divided by cortical thickness at each vertex, followed by threshold-free cluster enhancement (TFCE) multiple comparison correction. Binary logistic regression analysis was performed with DPD as the dependent variable, and significantly altered indicators as the independent variables. Receiver operating characteristic curves were constructed to compare the diagnostic performance of individual predictors and combinations using R and MedCalc software. DPD patients exhibited a significantly lower whole-brain functional-structural coupling index than NDPD patients and NC. Abnormal functional-structural coupling was primarily observed in the left inferior parietal lobule and right primary and early visual cortices in DPD patients. Receiver operating characteristic analysis revealed that the combination of cortical functional-structural coupling, surface-based ReHo, and thickness had the best diagnostic performance, achieving a sensitivity of 65% and specificity of 77.7%. This is the first study to explore the relationship between functional and structural changes in DPD patients and evaluate the diagnostic performance of these altered correlations to predict depression in Parkinson's disease patients. We posit that these changes in functional-structural relationships may serve as imaging biomarkers for depression in Parkinson's disease patients, potentially aiding in the classification and diagnosis of Parkinson's disease. Additionally, our findings provide functional and structural imaging evidence for exploring the neurobiological basis of depression in Parkinson's disease.

Atrophy patterns in hippocampus and amygdala subregions of depressed patients with Parkinson's disease

We aimed to explore the subregional atrophy patterns of the amygdala and hippocampus in Parkinson's disease (PD) with depression and their correlation with the severity of the depressive symptom. MRI scans were obtained for 34 depressed PD patients (DPD), 22 nondepressed PD patients (NDPD), and 28 healthy controls (HC). Amygdala and hippocampal subregions were automatically segmented, and the intergroup volume difference was compared. The relationships between the volumes of the subregions and depression severity were investigated. Logistic analysis and Receiver operator characteristic curve were used to find independent predictors of DPD. Compared with the HC group, atrophy of the bilateral lateral nucleus, left accessory basal nucleus, right cortical nucleus, right central nucleus, and right medial nucleus subregions of the amygdala were visible in the DPD group, while the right lateral nucleus subregion of the amygdala was smaller in the DPD group than in the NDPD group. The DPD group showed significant atrophy in the left molecular layer, left GC-DG, left CA3, and left CA4 subregions compared with the HC group for hippocampal subregion volumes. Also, the right lateral nuclei volume and disease duration were independent predictors of DPD. To sum up, DPD patients showed atrophy in multiple amygdala subregions and left asymmetric hippocampal subregions. The decreased amygdala and hippocampal subregion volumes were correlated with the severity of depressive symptoms. The volume of right lateral nuclei and disease duration could be used as a biomarker to detect DPD.

Hippocampal volume and resting-state functional connectivity on magnetic resonance imaging in patients with Parkinson and depression.

Recent structural and functional imaging studies of depression in Parkinson disease (DPD) have failed to reveal the relevant mechanism, and relatively few studies have been conducted on limbic systems such as the hippocampus. This study thus aimed to gain new insights into the pathogenesis of DPD by detecting the changes in the hippocampal structure and the resting-state functional connectivity (FC) of patients with DPD. This study included 30 patients with DPD (DPD group), 30 patients with nondepressed Parkinson disease (NDPD; NDPD group), and 30 normal controls (NCs; NC group) with no significant age or gender differences with the DPD group. The Hamilton Depression Rating Scale (HAMD) and three-dimensional T1-weighted imaging and blood oxygen level-dependent imaging data of all patients were collected. The hippocampal volumes were measured using MATLAB software (MathWorks). The correlation between hippocampal volume and the HAMD score in the DPD group was analyzed with Pearson correlation coefficient. The bilateral hippocampi were used as the regions of interest and as the seed points for FC. FC analysis was performed between the preprocessed functional data of the whole brain and the two seed points with Data Processing Assistant for Resting-State and Statistical Parametric Mapping 8 software, respectively. The correlation between FC and HAMD scores in the patients with DPD was determined using partial correlation analysis. Compared with those in the NC group and the NDPD group, the bilateral hippocampal volumes in the DPD group were significantly decreased (P<0.05). There was a negative correlation between the bilateral hippocampal volume and the HAMD score in the DPD group (P<0.05). Compared with that of the NDPD group, the FC of the right hippocampus with the right occipital lobe and left precuneus was reduced in the DPD group. In the DPD group, the FC values of the right hippocampus, right occipital lobe, and left anterior cuneiform lobe were negatively correlated with HAMD scores. The volume of bilateral hippocampi in patients with DPD is significantly decreased and negatively correlated with the severity of depressive disorder. The weakened FC of the right hippocampus to the right occipital lobe and the left precuneus may play an important role in the neurological basis of DPD.

Cortical gyrification pattern of depression in Parkinson's disease: a neuroimaging marker for disease severity?

Although the study of the neuroanatomical correlates of depression in Parkinson's Disease (PD) is gaining increasing interest, up to now the cortical gyrification pattern of PD-related depression has not been reported. This study was conducted to investigate the local gyrification index (LGI) in PD patients with depression, and its associations with the severity of depression. LGI values, as measured using FreeSurfer software, were compared between 59 depressed PD (dPD), 27 non-depressed PD (ndPD) patients and 43 healthy controls. The values were also compared between ndPD and mild-depressed PD (mi-dPD), moderate-depressed PD (mo-dPD) and severe-depressed PD (se-dPD) patients as sub-group analyses. Furthermore, we evaluated the correlation between LGI values and depressive symptom scores within dPD group. Compared to ndPD, the dPD patients exhibited decreased LGI in the left parietal, the right superior-frontal, posterior cingulate and paracentral regions, and the LGI values within these areas negatively correlated with the severity of depression. Specially, reduced gyrification was observed in mo-dPD and involving a larger region in se-dPD, but not in mi-dPD group. The present study demonstrated that cortical gyrification is decreased within specific brain regions among PD patients with versus without depression, and those changes were associated with the severity of depression. Our findings suggested that cortical gyrification might be a potential neuroimaging marker for the severity of depression in patients with PD.

Disrupted topologic efficiency of brain functional connectome in de novo Parkinson's disease with depression.

Growing evidence supports that depression in Parkinson's disease (PD) depends on disruptions in specific neural networks rather than regional dysfunction. According to the resting-state functional magnetic resonance imaging data, the study attempted to decipher the alterations in the topological properties of brain networks in de novo depression in PD (DPD). The study also explored the neural network basis for depressive symptoms in PD. We recruited 20 DPD, 37 non-depressed PD and 41 healthy controls (HC). The Graph theory and network-based statistical methods helped analyse the topological properties of brain functional networks and anomalous subnetworks across these groups. The relationship between altered properties and depression severity was also investigated. DPD revealed significantly reduced nodal efficiency in the left superior temporal gyrus. Additionally, DPD decreased five hubs, primarily located in the temporal-occipital cortex, and increased seven hubs, mainly distributed in the limbic cortico-basal ganglia circuit. The betweenness centrality of the left Medio Ventral Occipital Cortex was positively associated with depressive scores in DPD. In contrast to HC, DPD had a multi-connected subnetwork with significantly lower connectivity, primarily distributed in the visual, somatomotor, dorsal attention and default networks. Regional topological disruptions in the temporal-occipital region are critical in the DPD neurological mechanism. It might suggest a potential network biomarker among newly diagnosed DPD patients.

Autophagy markers, cognitive deficits and depressive symptoms in Parkinson's disease.

Depressive symptoms are common in Parkinson's disease (PD). The relationships between autophagy and PD or depression have been documented. However, no studies explored the role of autophagy markers associated with depressive symptoms in PD. Our study aimed to investigate the relationships between autophagy markers, cognitive impairments and depressive symptoms in PD patients.A total of 163 PD patients aged 50-80years were recruited. Plasma concentrations of autophagy markers (LC3-I, LC3-II and p62/SQSTM1) and glycolipid parameters were measured. Depressive symptoms, cognitive impairments, and motor function were assessed using the Hamilton Depression Rating Scale-17 (HAMD-17), the Montreal Cognitive Assessment (MoCA), and the Movement Disorders Society Unified Parkinson's Rating Scale Part III (MDS-UPDRS-III), respectively.There were no significant differences between depressed and non-depressed PD patients for LC3-I, LC3-II, LC3-II/LC3-I and p62/SQSTM1. After controlling confounding variables, LC3-II/LC3-I showed an independent relationship with depressive symptoms in PD patients (Beta = 10.082, t = 2.483, p = 0.014). Moreover, in depressive PD patients, p62/SQSTM1 was associated with MoCA score (Beta = -0.002, t = -2.380, p = 0.020); Further, p62/SQSTM1 was related to naming ability; in addition, p62/SQSTM1 was independently associated with delayed recall (Beta = -0.001, t = -2.452, p = 0.017).LC3-II/LC3-I was related to depressive symptoms in PD patients. In depressive PD patients, p62/SQSTM1 was associated with cognitive function, especially naming ability and delayed recall.

Functional and structural alterations as diagnostic imaging markers for depression in de novo Parkinson's disease.

Depression in Parkinson's disease (PD) is identified and diagnosed with behavioral observations and neuropsychological measurements. Due to the large overlaps of depression and PD symptoms in clinical manifestations, it is challenging for neurologists to distinguish and diagnose depression in PD (DPD) in the early clinical stage of PD. The advancement in magnetic resonance imaging (MRI) technology provides potential clinical utility in the diagnosis of DPD. This study aimed to explore the alterations of functional and structural MRI in DPD to produce neuroimaging markers in discriminating DPD from non-depressed PD (NDPD) and healthy controls (HC). We recruited 20 DPD, 37 NDPD, and 41 HC matched in age, gender, and education years. The patients' diagnosis with PD was de novo. The differences in regional homogeneity (ReHo), voxel-wise degree centrality (DC), cortical thickness, cortical gray matter (GM) volumes, and subcortical GM volumes among these groups were detected, and the relationship between altered indicators and depression was analyzed. Moreover, the receiver operating characteristic (ROC) analysis was performed to assess the diagnostic efficacy of altered indicators for DPD. Compared to NDPD and HC, DPD showed significantly increased ReHo in left dorsolateral superior frontal gyrus (DSFG) and DC in left inferior temporal gyrus (ITG), and decreased GM volumes in left temporal lobe and right Amygdala. Among these altered indicators, ReHo value in left DSFG and DC values in left ITG and left DSFG were significantly correlated with the severity of depression in PD patients. Comparing DPD and NDPD, the ROC analysis revealed a better area under the curve value for the combination of ReHo value in left DSFG and DC value in left ITG, followed by each independent indicator. However, the difference is not statistically significant. This study demonstrates that both functional and structural impairments are present in DPD. Among them, ReHo value of left DSFG and DC value of left ITG are equally well suited for the diagnosis and differential diagnosis of DPD, with a combination of them being slightly preferable. The multimodal MRI technique represents a promising approach for the classification of subjects with PD.

Identifying Depression in Parkinson's Disease by Using Combined Diffusion Tensor Imaging and Support Vector Machine.

ObjectiveTo investigate white matter microstructural alterations in Parkinson's disease (PD) patients with depression using the whole-brain diffusion tensor imaging (DTI) method and to explore the DTI–based machine learning model in identifying depressed PD (dPD).MethodsThe DTI data were collected from 37 patients with dPD and 35 patients with non-depressed PD (ndPD), and 25 healthy control (HC) subjects were collected as the reference. An atlas-based analysis method was used to compare fractional anisotropy (FA) and mean diffusivity (MD) among the three groups. A support vector machine (SVM) was trained to examine the probability of discriminating between dPD and ndPD.ResultsAs compared with ndPD, dPD group exhibited significantly decreased FA in the bilateral corticospinal tract, right cingulum (cingulate gyrus), left cingulum hippocampus, bilateral inferior longitudinal fasciculus, and bilateral superior longitudinal fasciculus, and increased MD in the right cingulum (cingulate gyrus) and left superior longitudinal fasciculus-temporal part. For discriminating between dPD and ndPD, the SVM model with DTI features exhibited an accuracy of 0.70 in the training set [area under the receiver operating characteristic curve (ROC) was 0.78] and an accuracy of 0.73 in the test set (area under the ROC was 0.71).ConclusionDepression in PD is associated with white matter microstructural alterations. The SVM machine learning model based on DTI parameters could be valuable for the individualized diagnosis of dPD.

Altered Functional Connectivity of Ventral Striatum Subregions in De-novo Parkinson’s Disease with Depression

Although various studies have reported a high prevalence of depression among Parkinson's disease (PD) patients, the pathophysiological mechanism of depression in PD (DPD) is still unclear. The core region of the reward network, the ventral striatum (VS), is critical in the occurrence and development of DPD. This study aimed to explore the altered functional connectivity (FC) of VS subregions in DPD. We recruited 20 DPD patients, 37 non-depressed PD (NDPD) patients, and 41 healthy controls (HC) matched in age, gender, and years of education. The patients' diagnosis with PD was de-novo. We then used resting-state functional magnetic resonance imaging to detect the FC differences of VS subregions among these groups. The FC between the left ventral caudate (vCa_L) and the left middle occipital gyrus (MOG.L) was significantly increased in DPD than in NDPD patients or HC. Compared with HC, NDPD patients exhibited significantly increased FCs between bilateral ventromedial putamen and the left paracentral lobule, the right ventromedial putamen (vmPu_R), and the right precentral gyrus, the vmPu_R, and the left precuneus. Besides, a significant negative correlation was found between the FC values of the vCa_L with the MOG.L and the HAMD-17 scores in the DPD group. The hyperconnectivity between vCa_L and the MOG.L might be viewed as a compensatory mechanism for depression in the early stage of PD. This study provides new insight into the neural mechanism of depression in the early stage of PD and contributes to explore the potential neuroimaging markers for DPD.

Impaired white matter microstructure associated with severe depressive symptoms in patients with PD.

Depression is a common occurrence in patients with Parkinson's disease (PD); however, its pathophysiology is still unclear. This study assessed the association between the integrity of white matter and depressive symptoms in patients with PD. 67 patients with PD were divided into a non-depressed PD group (ndPD, n = 30) and a depressed PD group (dPD, n = 37). The dPD group was further subdivided into a mild-moderately depressed PD (mdPD, n = 22) and a severely depressed PD group (sdPD, n = 15). Tract-Based Spatial Statistics was used to compare fractional anisotropy (FA) between groups. Region-of-interest analysis was used to explore changes in diffusivity indices in the regions showing FA abnormalities. The sdPD patients exhibited significantly reduced FA in the left superior longitudinal fasciculus, uncinate fasciculus, anterior corona radiata, corticospinal tract, and bilateral inferior fronto-occipital fasciculus when compared with the ndPD patients, but the decreased FA was within a smaller area when compared with the mdPD patients. No significant difference in FA was found between the mdPD and ndPD groups. Among the dPD patients, FA values in the left superior longitudinal fasciculus negatively correlated with BDI scores. Impaired white matter integrity in the prefronto-limbic/temporal circuitry, mainly in the left hemisphere, is associated with severe, but not mild-moderate depressive symptoms in patients with PD.

Depression and Related Factors in Patients with Parkinson's Disease at High Altitude.

PurposeDepression seems to aggravate progression of Parkinson’s disease (PD). Hypoxia stress may be one of the pathogenic factors leading to PD. We investigated the characteristics of PD and factors related to Parkinson’s disease depression (PDD) at high altitude (mean altitude ≥2300 m).Patients and MethodsTotally 221 PD patients of three different nationalities (Han, Hui, and Tibetan) were recruited in a high-altitude hospital. Depression was present in 55.6% of them. Patient data were examined, including demographic information, medical history, disease duration and family history. Psychopathological characteristics and motor signs were assessed by the Hamilton Depression scale (HAMD) and scales for motor and non-motor symptoms in the Unified Parkinson’s Disease Rating Scale (UPDRS). Progression of PD was evaluated by the modified Hoehn and Yahr (H-Y) staging system.ResultsMean age (47.1% men) was 68.25±13.67 years old, with disease duration of 4.18±5.13 years and median H-Y scores 2.07±0.97 points. Among three different nationalities, PD rate was 69.2% in Han nationals, 17.6% in Hui nationals and 13.1% in Tibetans of 221 PD patients. Compared with the non-depressed PD group, female, no-smoking and living alone rates, and dysphagia, pain, H-Y stage, ADL, UPDRS-I, UPDRS-III, HAMA, and PSQI scores were significantly increased in the PDD group, while MMSE scores were significantly decreased (P<0.05 or P<0.01). PD patients of Han and Hui nationalities had increased depression rates compared with Tibetan individuals (P<0.05). Compared with the mild depression group, the moderate and severe depression groups had significantly increased salivation, dysphagia, H-Y stage, UPDRS-I, UPDRS-III, HAMA, and PSQI scores (P<0.05 or P<0.01). Living alone rates and ADL scores were increased in the severe depression group (P<0.05). Logistic regression analysis showed that living alone (OR=19.833, 95% CI: 2.758–142.624, P<0.01), UPDRS-III score (OR=1.079, 95% CI: 1.009–1.153, P<0.05), and PSQI score (OR=1.538, 95% CI: 1.347–1.755, P<0.001) were risk factors for PDD. Male gender (OR=0.292, 95% CI: 0.112–0.763, P<0.05) was a protective factor in PDD.ConclusionPDD is associated with gender, ethnicity, loneliness, non-motor symptoms (NMSs), motor symptoms, and disease severity, and depression severity. Living alone, dyskinesia, and sleep disorder are risk factors for PDD at high altitude. A relative protection against depression was observed in the Tibetan population.

Serum BDNF discriminates Parkinson's disease patients with depression from without depression and reflect motor severity and gender differences.

To evaluate the diagnostic value of serum Brain-derived neurotrophic factor (BDNF) levels for discriminating PD with depression from without depression, and to investigate whether serum BDNF levels were associated with motor severity and gender in depressed PD patients. Demographic and clinical data were collected from 122 PD patients with depression, 137 without depression and 110 healthy controls. All participants' serum BDNF concentrations were measured. Their motor abilities and activity were assessed by the Unified PD Rating Scale Part III (UPDRS III) score and the Hoehn and Yahr (H-Y) stage. Depression was scored using the 17-item Hamilton Rating Scale for Depression (HAMD-17). Associations were analyzed with multivariate regression. The serum BDNF levels were lower in depressed PD patients compared to non-depressed PD patients and controls (p < 0.001). The BDNF levels were negatively correlated with UPDRS III score (r = -0.54, p < 0.001) and H-Y stage (r = -0.45, p < 0.001). Decreased BDNF levels were associated with women only among depressed PD patients (r = 0.45, p < 0.001). The HAMD-17 score was negatively correlated with BDNF levels (r = -0.59, p < 0.001), and positively associated with UPDRS III score (r = 0.51, p < 0.001). Multiple regression analysis demonstrated that in the depressed PD patients, female, H-Y stage and UPDRS III score were independent contributors to the BDNF levels (p < 0.001; p = 0.006; p = 0.03, respectively), BDNF and UPDRS III score were independent contributors to HAMD-17 score (p < 0.001, p = 0.01, respectively). Decreased serum BDNF levels may be a useful clinical biomarker of depression in PD patients. Serum BDNF may serve as a potential biomarker for motor severity of PD patients with depression, especially in female.

Improving Self-Awareness of Motor Symptoms in Patients With Parkinson's Disease by Using Mindfulness - A Study Protocol for a Randomized Controlled Trial.

ObjectiveThis study aims to increase self-awareness in patients with Parkinson’s disease (PD) using a newly developed mindfulness-based intervention, tailored for the specific needs of PD patients. Its impact on self-awareness and patients’ daily lives is currently being evaluated.BackgroundRecently, the phenomenon of impaired self-awareness for motor symptoms (ISAm) and some non-motor symptoms has been described in PD. ISAm can negatively influence patients’ daily lives, e.g., by affecting therapy adherence, and is therefore the main focus of this study. The main goal is the development of IPSUM (“Insight into Parkinson’s Disease Symptoms by using Mindfulness”), a PD-specific intervention for increasing patients’ mindfulness and thereby reducing ISAm.MethodsThe effectiveness of IPSUM is evaluated by comparison of an intervention group with a waitlist-control group. A pre-post design with an additional 8-week follow-up measurement is applied, resulting in three measurement points: before, directly after and 8 weeks after completing the intervention protocol. In total, up to 180 non-depressed PD patients without severe cognitive impairment (non-demented) will be included. The primary outcome is a quantitative score for measuring ISAm. Secondary outcome measures are affective changes, neuropsychological performance and self-awareness of cognition. At pre- and post-measurement an fMRI scan is performed to connect behavioral and neurobiological findings. At post- and follow-up-measurement each patient will take part in a semi-structured interview to explore IPSUM’s impact on self-awareness and patients’ everyday lives.ResultsThe conception of the intervention protocol is finished, the resulting 8-week program is presented in detail. It has successfully been tested in the first group of patients, their feedback so far was quite promising. Recruitment is ongoing and a first interim analysis will be performed once 30 patients have completed IPSUM.ConclusionFor the first time, the intervention protocol of IPSUM has successfully been tested in a group of PD patients. As the study goes on, more quantitative data is collected for statistical analyses to evaluate its effectiveness. More qualitative data is collected to evaluate feasibility and effectiveness. We hope for this intervention to be capable of reducing the patients’ ISAm and improving their quality of life on many levels.

Damaged Insula Network Contributes to Depression in Parkinson's Disease.

BackgroundDepression is common in patients with Parkinson’s disease (PD). Our previous studies suggest that depressed PD patients have altered insula structures. It is, however, still unknown whether the altered structures cause disruption of insula functional networks, further contributing to depression in PD.MethodsIn the present study, 17 depressed PD patients, 17 non-depressed PD patients, and 17 normal controls were enrolled. All subjects went through neurological and psychiatric clinical assessments. Resting-state functional magnetic resonance imaging and seed-based insula functional analyses were performed to examine the insula functional connectivity alterations in PD patients.ResultsWe found that compared with normal controls, PD patients exhibited significantly decreased insula functional connectivity widely across the whole brain. Compared with non-depressed PD patients, depressed patients showed further decreased functional connectivity in the middle frontal gyrus and inferior parietal lobe. Furthermore, connectivity between the left anterior insula and middle frontal gyrus was positively correlated with the cognitive scale score.ConclusionThese results suggest that insula networks were severely damaged in PD patients, and that the disrupted connection between the salience network and executive control network might contribute to depression in PD.

Changed Resting-State Brain Signal in Parkinson's Patients With Mild Depression.

Background: Depression is reported to occur 5–10 years early than the onset of motor symptoms in Parkinson (PD) patients. However, markers for early diagnosis of PD in individuals with sub-clinical depression still remain to be identified.Purpose: This study utilized Regional Homogeneity (ReHo) to investigate the alterations in resting state brain activities in Parkinson (PD) patients with different degrees of depression.Methods: Twenty non-depressed PD patients, twenty mild to moderately depressed PD patients, and thirteen severely depressed PD patients were recruited. Hamilton Depression Scale (HDS) and the Beck Depression Inventory (BDI) were assessed depression. Resting-state functional magnetic resonance imaging (rs-MRI) was analyzed with ReHo.Results: PD patients with mild to moderate depression had decreased ReHo in the left dorsal anterior cingulate cortex when compared with PD patients without depression. PD patients with severe depression exhibited increased ReHo in the left inferior prefrontal gyrus and right orbitofrontal area when compared with PD patients with mild to moderate depression. ReHo values in the bilateral supplementary motor area (SMA) in PD patients with severe depression was also increased when compared with PD patients without depression.Conclusions: This study suggests that rs-MRI with ReHo analysis can detect early changes in brain function that associate with depression in PD patients, which could be biomarkers for early diagnosis and treatment of PD related depression.

Microstructural White Matter Characteristics in Parkinson's Disease With Depression: A Diffusion Tensor Imaging Replication Study.

Background: Clarifying the neuropathology of depression as a symptom of Parkinson's disease (PD) has been the goal of recent neuroimaging studies; however, results have been conflicting and lack replication. The purpose of the current study was to replicate recent methods that have used diffusion tensor imaging (DTI) to compare individuals with PD with and without depression and to extend previous findings to allow for a better understanding of the results.Methods: Thirty-seven participants with de novo PD were retrieved from the Parkinson's Progression Marker's Initiative (PPMI) and were separated into a depressed PD group (dPD) or a non-depressed PD group (ndPD). Groups were determined based on scores on the Geriatric Depression Scale Short Form (GDS-15). Initially, a replicated cut off score of ≥ 5 for dPD and <5 for ndPD was applied. To better understand the results, we secondarily applied a more extreme group analysis with ≥ 9 for dPD and 0 for ndPD. White matter integrity between groups was compared between groups using tract-based spatial statistics.Results and Conclusion: The current study did not reveal significant differences in white matter microstructure between dPD and ndPD groups at the whole brain level or in specific regions of interest. The extreme group results were consistent. These findings did not replicate previous work that found reduced white matter integrity in limbic prefrontal regions in dPD relative to ndPD. The current study highlights the need for more replications of neuroimaging research.

New insights into facial emotion recognition in Parkinson's disease with and without mild cognitive impairment from visual scanning patterns

BackgroundRecognizing emotional facial expressions is crucial for social interactions. Cognitive impairment and oculomotor abnormalities are common features of Parkinson's disease (PD) which may contribute to the performance in facial emotion recognition (FER) in PD. ObjectiveThe aim of this study was to analyze eye movement behavior during a facial emotion recognition (FER) task with respect to cognitive state in PD patients and healthy controls. MethodsEye movements of 24 non-demented, non-depressed PD patients (12 with intact cognitive functions and 12 with Mild Cognitive Impairment (MCI) according to MDS task force criteria level 2), and 12 age-, sex and education-matched healthy controls were recorded during visual exploration of 28 emotional (happiness, surprise, disgust, anger, fear and sadness) and neutral faces. Participants were asked to identify the displayed emotion out of a sevenfold multiple choice question. ResultsPD-MCI patients showed reduced FER with specific impairment of anger recognition. Although the scanned area of PD patients with intact cognition was significantly restricted, they did not differ in FER from healthy subjects. While healthy subjects and cognitively intact PD patients scanned faces with preference for mouth and eyes, patients with PD-MCI tended to look at the center of the face and spent significantly less time fixating the mouth. ConclusionsIneffective visual exploration may contribute to impaired emotion recognition in PD. Visual scanning of emotional faces is altered in PD even in the absence of cognitive impairment. The progression to PD-MCI may result in further deterioration of scanning behavior and FER impairment.

Plasma levels of brain-derived neurotrophic factor in patients with Parkinson disease: A systematic review and meta-analysis

BackgroundBrain-derived neurotrophic factor (BDNF) is an abundant neurotrophin in the adult brain. Serum BDNF levels might be used as a proxy for its central expression. Considering conflicting reports, we aimed to answer “How do serum/CSF levels of BDNF change in patients with PD?”. MethodsWe conducted a comprehensive search in MEDLINE, EMBASE and SCOPUS databases including 12 eligible studies. Five studies compared BDNF in serum of PD patients versus healthy controls (HC) and 3 studies provided BDNF levels in sera of non-depressed and depressed PD patients (NDPD and DPD). Review Manager and Software version 3.0 were used for meta-analysis and meta-regressions. Mean difference (MD) was used for measurement of effect size. ResultsPD patients had reduced serum BDNF levels compared to HC (MD = -2.99 ng/mL). Serum BDNF was highest in DPD patients compared to HC (MD = -4.83 ng/mL), with no difference between DPD and NDPD patients in serum BDNF levels. Among co-variates that were eligible for meta-regression, age, sex, and Hoehn and Yahr (H&Y) motor stage had significant positive associations with the effect size in the difference of serum BDNF between patients and HC. ConclusionsPD patients had reduced serum BDNF levels compared to HC, regardless of presence of co-morbid depression. PD is at least equally effective in reducing serum BDNF levels as depression. Motor progression predicts serum BDNF downregulation in PD. Acute exercise improves motor function and depressive symptoms in PD probably via BDNF upregulation. The paradoxical rise in serum BDNF in advance PD is probably compensatory in nature.

Altered Cortico-Limbic Network Connectivity in Parkinsonian Depression: The Effect of Antidepressants.

Depression is a common comorbidity of Parkinson's disease (PD); however, the impact of antidepressant status on cortical function in parkinsonian depression is not fully understood. While studies of resting state functional MRI in major depression have shown that antidepressant treatment affects cortical connectivity, data on connectivity and antidepressant status in PD is sparse. We tested the hypothesis that cortico-limbic network (CLN) resting state connectivity is abnormal in antidepressant-treated parkinsonian depression. Thirteen antidepressant-treated depressed PD and 47 non-depressed PD participants from the Parkinson's Progression Markers Initiative (PPMI) database were included. Data was collected using 3T Siemens TIM Trio MR scanners and analyzed using SPM and CONN functional connectivity toolbox. Volumetric analysis was also performed using BrainSuite. We found decreased connectivity in the antidepressant-treated depressed PD group when compared to non-depressed PD between the left frontal operculum and bilateral insula, and also reduced connectivity between right orbitofrontal cortex and left temporal fusiform structures. Increased depression scores were associated with decreased insular-frontal opercular connectivity. No ROI volumetric differences were found between groups. Given the relationship between depression scores and cortico-limbic connectivity in PD, the abnormal insular-frontal opercular hypoconnectivity in this cohort may be associated with persistent depressive symptoms or antidepressant effects.

Cognitive correlates of “pure apathy” in Parkinson's disease

IntroductionPrevious studies exploring the association between apathy and cognitive deficits in Parkinson's disease (PD) employed scales and questionnaires for apathy, which did not control for the possible confounding effect of motor symptoms. Here we investigated the cognitive correlates of “pure apathy” by the Dimensional Apathy Scale, which allows us to assess apathy minimizing the influence of motor symptoms. MethodsConsecutive PD outpatients referred to our centre were screened. All participants underwent a neuropsychological battery to assess verbal memory, executive functions and visuospatial abilities, apathy and depressive symptoms. ResultsWe enrolled 56 non-depressed and non-demented PD patients, of whom 28 were apathetic and 28 were not. The two groups did not differ on demographic and clinical aspects; apathetic PD patients performed worse than non-apathetic PD patients on the part A, B and B-A of Trail Making Test and the interference task of Stroop test. No significant differences were found on memory and perceptual visuospatial tasks. ConclusionsOur results demonstrated that “pure apathy” is associated with more severe executive dysfunctions such as alteration of set-shifting and inhibitory control, which are mediated by prefrontal cortex and subcortical regions (i.e. basal ganglia). Our findings also supported the hypothesis that co-occurrence of apathy and executive deficits may be the epiphenomenon of damage in prefrontal-striatal cortical circuitries connecting dorsolateral prefrontal cortex, anterior cingulate cortex and basal ganglia.